Filed 11/14/2018 1:30 PM

Reba Squyres, District Clerk

Angelina County, Texas
By: Brittany Crawford,
CV-00785-18-11 Deputy Clerk
CAUSE NO.

COUNTY OF ANGELINA, § IN THE DISTRICT COURT

§
Plaintiff, §
§
vs. § JUDICIAL DISTRICT
§
PURDUE PHARMA L.P.; §
PURDUE PHARMA INC.; §
THE PURDUE FREDERICK COMPANY; §
JOHNSON & JOHNSON; § ANGELINA COUNTY, TEXAS
JANSSEN PHARMACEUTICALS, INC.; §
ORTHO-MCNEIL-JANSSEN §
PHARMACEUTICALS, INC. n/k/a §
JANSSEN PHARMACEUTICALS, INC.; §
JANSSEN PHARMACEUTICA INC. n/k/a §
JANSSEN PHARMACEUTICALS, INC.; §
ENDO HEALTH SOLUTIONS INC.; §
ENDO PHARMACEUTICALS, INC.; and §
DOES 1 – 100, INCLUSIVE, §
§
Defendants. §

PLAINTIFF’S ORIGINAL PETITION AND JURY DEMAND

TO THE HONORABLE JUDGE OF SAID COURT:

Plaintiff, the County of Angelina, Texas, by and through the undersigned attorneys,

(hereinafter “Angelina County” or “County”) against Defendants Purdue Pharma L.P., Purdue

Pharma Inc., The Purdue Frederick Company, Johnson & Johnson, Janssen Pharmaceuticals, Inc.,

Ortho-McNeil-Janssen Pharmaceuticals, Inc. n/k/a Janssen Pharmaceuticals, Inc., Janssen

Pharmaceutica Inc. n/k/a Janssen Pharmaceuticals, Inc., Endo Health Solutions Inc., Endo

Pharmaceuticals, Inc., and Does 1 – 100, alleges as follows:

I. INTRODUCTION

1. The United States is in the midst of an opioid epidemic caused by Defendants’

fraudulent marketing, sales, and distribution of prescription opioids (“opioids”) that has resulted

PLAINTIFF’S ORIGINAL PETITION 1

in addiction, criminal activity, and loss of life.1 Americans “consume 85% of all the opioids in the

world” and are “the most medicated country in the world . . . .”2 The opioid crisis has been

described as “the AIDS epidemic of our generation, but even worse.”3 On October 26, 2017,

President Donald Trump “declared a nationwide public health emergency to combat the opioid

crisis.”4

2. In 1997, each person in the United States, on average, consumed 96 mg morphine

equivalents. In 2010 that number increased to 710 mg per person.5 This amount has been estimated

as the equivalent to 7.1 kg of opioids per 10,000 people – or enough to supply each American with

5 mg of hydrocodone every 6 hours for 45 days.6

3. It’s no surprise that in 2016 alone, health care providers wrote more than 289

million prescriptions for opioids, enough for every adult in the United States to have more than

one bottle of pills.7 The prescription rate in Angelina County is substantially higher than the

national average.8

4. Unfortunately, using opioids too often leads to addiction and overdose from

opioids. It was estimated as early as 2001 that up to 40% of chronic pain patients were addicted to

opioid pain medication. 9 Almost 2 million Americans were addicted to opioids in 2014.10 To put

1
L. Manchikanti, Opioid Epidemic in the United States, Pain Physician, Jul. 2012, at 1,
www.painphysicianjournal.org, attached hereto as Exhibit A.
2
David Wright, Christie on Opioids: “This is the AIDS Epidemic of Our Generation, but even Worse,” CNN, Oct.
27, 2017, available at http://www.cnn.com/2017/10/27/politics/chris-christie-opioid-commission-aids-
cnntv/index.html; Manchikanti, Ex. A, at 16 (“Gram for gram, people in the United States consume more narcotic
medication than any other nation worldwide.”).
3
Wright, supra.
4
Dan Merica, What Trump’s Opioid Announcement Means – and Doesn’t Mean, CNN, Oct. 26, 2017, available at
http://www.cnn.com/2017/10/26/politics/national-health-emergency-national-disaster/index.html.
5
Manchikanti, Ex. A, at 14.
6
Id.
7
Prevalence of Opioid Misuse, BupPractice, Sept. 7, 2017, available at https://www.buppractice.com/node/15576.
8
Center for Disease Control, available at https://www.cdc.gov/drugoverdose/maps/rxrate-maps.html.
9
Prescription Drugs: Abuse and Addiction, National Institute of Drug Abuse (NIH Publication), Jul. 2001, at 13.
10
National Survey on Drug Use and Health, Substance Abuse and Mental Health Services Administration, 2014.

PLAINTIFF’S ORIGINAL PETITION 2

the opioid crisis in perspective, the statistics demonstrate:

· Roughly 21 to 29 percent of patients prescribed opioids for chronic pain misuse

them;

· Between 8 and 12 percent develop an opioid use disorder; and

· About 80 percent of people who use heroin first misused prescription opioids.11

5. In 2014, more people died from drug overdoses than in any other year. Currently

more than 90 Americans die every day after overdosing on opioids.12 The Texas Legislature has

found “that deaths resulting from the use of opioids and other controlled substances constitute a

public health crisis.”13

6. In fact, accidental drug overdose deaths, of which reportedly at least two-thirds are

opioid overdoses, are the leading cause of death for Americans under the age of 50. And these

accidental opioid drug overdose deaths exceed the number of deaths caused by cars or guns. A

report from the CDC found that from July 2016 to September 2017, emergency visits due to

suspected opioid overdoses continued to climb approximately 30% across the nation.14 The

increase was seen in adults of all age groups and in men and women in all geographic areas.15

7. Over the next decade, the average number of deaths due to opioids is expected to

be 500,000.16 Proof that the opioid epidemic is far from slowing is the latest statistic that

11
Opioid Overdose Crisis, National Institute on Drug Abuse, Jan. 2018, available at
https://www.drugabuse.gov/drugs-abuse/opioids/opioid-overdose-crisis.
12
Id.
13
Tex. Att’y Gen. Op. No. KP-0168 (2017), citing Act of May 26, 2017, 85th Leg., R.S., ch. 534, § 3, 2017 Tex.
Sess. Law Serv. 1467, 1468.
14
Jacqueline Howard, ER Visits for Opioid Overdose up 30%, CDC Study Finds, CNN, Mar. 6, 2018. 
15
Id.
16
Max Blau, STAT forecast: Opioids Could Kill Nearly 500,000 American in the next Decade, STAT, June 27,
2017, available at https://www.statnews.com/2017/06/27/opioid-deaths-forecast/; see also Wes Rapaport,
Advocates for Painkiller Advocates Wants Society to Meet Them Halfway, Big Country, Feb. 18, 2018 (stating the
number of opioid overdose deaths is going to go up for at least several more years and explaining how Operation
Naloxone has administered more than $1 million of the powerful antidote).

PLAINTIFF’S ORIGINAL PETITION 3

approximately 72,000 Americans died from drug overdoses last year in 2017.17 This increase is

due to a growing number of Americans using opioids and the opioids themselves are becoming

more deadly.18 The economic burden caused by opioid abuse in the United States is at least $78.5

billion,19 including lost productivity and increased social services, health insurance costs,

increased criminal justice presence and strain on judicial resources, and substance abuse treatment

and rehabilitation.20 In 2015, Texas “had the second highest total healthcare costs from opioid

abuse in the nation ($1.96 billion) . . . .”21

8. This epidemic did not occur by chance. Defendants manufacture, market, distribute,

and sell prescription opioids, including, but not limited to, brand-name drugs like OxyContin,

Opana, Percocet, Percodan, Duragesic, Ultram, Ultracet, and generics like oxycodone,

oxymorphone, hydromorphone, hydrocodone, fentanyl, and tramadol, which are powerful

narcotics.

9. Historically, opioids were considered too addictive and debilitating for treating non-

cancer chronic pain,22 such as back pain, migraines, and arthritis, and were used only to treat short-

term acute pain or for palliative or end-of-life care.

10. By the late 1990s or early 2000s, however, each Defendant began a marketing

scheme to persuade doctors and patients that opioids were not addictive and should be used

17
Margot Sanger-Katz, Bleak New Estimates in Drug Epidemic: A Record 72,000 Overdose Deaths in 2017, The
New York Times, Aug. 15, 2018, https://www.nytimes.com/2018/08/15/upshot/opioids-overdose-deaths-rising-
fentanyl.html (representing a 9.5 percent increase from 2016).
18
Id.
19
CDC Foundation’s New Business Pulse Focuses on Opioid Overdose Epidemic, Centers for Disease Control and
Prevention, Mar. 15, 2017, available at https://www.cdc.gov/media/releases/2017/a0315-business-pulse-
opioids.html.
20
Opioid Overdose Crisis, supra.
21
Kerry Craig, Opioid Addiction Results in one Woman’s Daily Struggle, Sulphur Springs News-Telegram, Oct. 7,
2017, available at https://www.ssnewstelegram.com/news/opioid-addiction-results-in-one-woman-s-daily-
struggle/article_bded4eoa-ab80-11e7-a252-d3f304e26628.html. 
22
“Chronic pain” means non-cancer pain lasting three months or longer.

PLAINTIFF’S ORIGINAL PETITION 4

ubiquitously and perpetually to treat moderate, non-cancer chronic pain.23 Defendants’ efforts to

“increase opioid use” and their campaign emphasizing “the alleged undertreatment of pain

continue to be significant factors of the [opioid] escalation.”24 Defendants reassured the medical

community that opioids were not addictive and doctors prescribed them at a higher rate.25

Consequently, the National Institute of Drug Abuse attributes the opioid crises to Defendants’

successful marketing campaign.26 Each Defendant spent, and continues to spend large sums of

money to promote the benefits of opioids for non-cancer moderate pain while trivializing or even

denying their risks.

11. The Defendants’ promotional messages deviated substantially from any approved

labeling of the drugs and caused prescribing physicians and consuming patients to underappreciate

the health risks, and to overestimate the benefits of opioids.

12. Contrary to the language of their drugs’ labels, Defendants falsely and misleadingly,

in their marketing: (1) downplayed the serious risk of addiction; (2) promoted and exaggerated the

concept of “pseudoaddiction” thereby advocating that the signs of addiction should be treated with

more opioids; (3) exaggerated the effectiveness of screening tools in preventing addiction; (4)

claimed that opioid dependence and withdrawal are easily managed; (5) denied the risks of higher

opioid dosages; and (6) exaggerated the effectiveness of “abuse-deterrent” opioid formulations to

prevent abuse and addiction.

23
See e.g., Opioid Overdose Crisis, National Institute on Drug Abuse, Jan. 2018, available at
https://www.drugabuse.gov/drugs-abuse/opioids/opioid-overdose-crisis (explaining the greater rate of prescribing
opioids due to misinformation to physicians, which led to a diversion and misuse of opioids before anyone knew
opioids were highly addictive).
24
Manchikanti, Ex. A, at 1.
25
CDC/NCHS, National Vital Statistics System, Mortality, CDC Wonder, Atlanta, Ga: US Department of Health
and Human Services, 2017, available at https://wonder.cdc.gov. 
26
 See id. 

PLAINTIFF’S ORIGINAL PETITION 5

 13. Defendants disseminated these falsehoods through ads, sales representatives, and/or

hand-picked physicians who supported Defendants’ message. Sales representatives, working at

Defendants’ behest, promoted highly addictive opioids through souvenirs and toys including, but

not limited to, opioid brand-bearing stuffed plush toys, dolls, coffee cups, fanny packs, water

bottles, notepads, pens, refrigerator magnets, clocks, letter openers, rulers, daytime planners, bags,

puzzles, posters, hand-held calculators, clipboards, highlighters, flashlights, key chains, clothing,

reflex mallets, and mock-ups of the United States Constitution.

14. Defendants also used third parties they controlled by: (a) funding, assisting,

encouraging, and directing doctors, known as “key opinion leaders” (“KOLs”) and (b) funding,

assisting, directing, and encouraging seemingly neutral and credible professional societies and

patient advocacy groups (referred to hereinafter as “Front Groups”).

15. Defendants worked with KOLs and Front Groups to taint the sources that doctors

and patients relied on for ostensibly “neutral” guidance, such as treatment guidelines, Continuing

Medical Education (“CME”) programs, medical conferences and seminars, and scientific articles.

Through their individual and concerted efforts, Defendants convinced doctors that instead of being

addictive and unsafe for long-term use in most circumstances, opioids were required in the

compassionate treatment of chronic pain, which Defendants termed an epidemic in America.

16. Defendants’ aggressive marketing of opioids for chronic pain is “based on unsound

science and blatant misinformation, and accompanied by the dangerous assumptions that opioids

are highly effective and safe, and devoid of adverse events when prescribed by physicians.”27

Nevertheless, Defendants’ marketing was effective and, by 2011 there were 136.7 million

prescriptions for hydrocodone alone, with all opioids exceeding 238 million.28 Data demonstrates

27
Manchikanti, Ex. A, at 1-4.
28
Id.

PLAINTIFF’S ORIGINAL PETITION 6

that “[o]ver 90% of patients received opioids for chronic pain management.”29

17. Essentially each Defendant ignored science and consumer health for profits.

Defendants’ efforts were so successful that opioids are now the most prescribed class of drugs

generating $11 billion in revenue for drug companies in 2014 alone. Sales for Purdue’s OxyContin

grew from $48 million in 1996 to $1.1 billion in 2000 after it successfully and aggressively

marketed and promoted its opioid.30 In fact, OxyContin was a “leading drug of abuse” by 2004

through its availability.31 Even after Purdue reached a $600 million federal settlement in 2007, the

settlement failed to impact what is a “$13-billion-a-year opioid industry.”32

18. As a direct and foreseeable consequence of Defendants’ misrepresentations and

misleading marketing campaign to Angelina County physicians and residents regarding the safety

and efficacy of using opioids for chronic non-cancer pain that resulted in an oversupply of opioids,

Angelina County has spent and continues to spend large sums of money combatting the public

health crisis.

19. The money Angelina County has spent comes directly from its taxpayers. These

taxpayers include Angelina County physicians, who passed on Defendants’ misleading safety and

efficacy information and prescribed more opioids to taxpaying residents in Angelina County.

These taxpayers also included Angelina County residents who either suffered the addictive effects

of consuming opioids or overdosed using Defendants’ opioids that had been over-prescribed and

over-supplied to Angelina County as intended by Defendants herein. Thus, this group of Angelina

County residents has suffered not only injury to property, but also bodily injury, as a result of

29
Manchikanti, Ex. A, at 1-4.
30
Art Van Zee, M.D., The Promotion and Marketing of OxyContin: Commercial Triumph, Public Health Tragedy,
99 Am. J. Public Health 221, Feb. 2009, at 1, attached hereto as Exhibit B.
31
Zee, supra.
32
Rebecca L. Haffajee, J.D., Ph.D., M.P.H. and Michelle M. Mello, J.D., Ph.D., Drug Companies’ Liability for the
Opioid Epidemic, N. Engl. J. Med., Dec. 14, 2017, at 2305.

PLAINTIFF’S ORIGINAL PETITION 7

Defendants’ misconduct in the false promotion and/or over-supply of prescription opioids.

20. Angelina County has spent and continues to spend large sums of money combatting

the opioid crisis created by Defendants’ negligent and fraudulent marketing campaign. Across the

country, including Texas, increased opioid prescribing has caused and continues to cause an

increase in overdoses and death. Defendants tracked the CDC data and knew that the more they

promoted opioid prescribing and distributed more opioids that non-therapeutic outcomes, such as

overdose, addiction, and criminality would occur. By 2010, enough opioids had been sold to

medicate every American adult with a typical dose of 5 mg of hydrocodone every 4 hours for 1

month.33 The increased use of opioids has contributed to the increased rate of overdose deaths and

nonmedical use with the varying rates of sales in each state impacting the outcomes in each state.34

“Given that 3% of physicians accounted for 62% of the [opioids] prescribed in one study, the

proliferation of high-volume prescribers can have a large impact on state use of [opioids] and

overdose death rates.”35 Not surprisingly, “[l]arge increases in overdoses involving the types of

drugs sold by illegitimate pain clinics (i.e., ‘pill mills’) have been reported in Florida and Texas.”36

In Angelina County, the prescription rate per 100 people in 2015 was 105.4, which means that

every man, woman, and child in Angelina County could have had at least one bottle of opioids.37

From 2015 - 2016, there were 10 – 11.9 deaths per 100,000 people reported from drug overdoses.38

A substantial number of those overdose deaths were a result, in whole or in part, of opioid

ingestion. Defendants’ marketing misconduct, as well as Defendants’ efforts to sell more

prescription opioids than can be consumed therapeutically, were natural and foreseeable causes of

33
Center for Disease Control, Vital Signs: Overdoses of Prescription Opioid Pain Relievers – United States, 1999-
2008, Morbidity and Mortality Weekly Report (MMWR), Nov. 4, 2011.
34
Id.
35
Id.
36
Id.
37
Center for Disease Control, available at https://www.cdc.gov/drugoverdose/maps/rxrate-maps.html.
38
Center for Disease Control, available at https://www.cdc.gov/nchs/data-visualization/drug-poisoning-mortality.

PLAINTIFF’S ORIGINAL PETITION 8

overdose deaths and injuries in Angelina County.

21. As a direct and foreseeable consequence of Defendants’ conduct described

regarding prescription opioids, Angelina County has committed and continues to commit resources

to provide and pay additional health care, law enforcement, social services, public assistance,

pharmaceutical care and other services necessary for its residents.

II. RULE 47 STATEMENT OF MONETARY RELIEF SOUGHT

22. Per Rule 47 of the Texas Rules of Civil Procedure, the County states that although the

full measure of its damages is still being calculated, its damages caused by Defendants’ acts and

omissions exceed $1,000,000 but are believed to be less than $100,000,000. Accordingly, at this time

in the litigation, Angelina County states that it is seeking monetary relief for an amount greater than

$1,000,000 and less than $100,000,000, the rightful and just amount to be determined by the jury.

III. STANDING

23. Angelina County has standing to bring this lawsuit because it has suffered an injury-

in-fact caused by Defendants’ misconduct, and that harm can be redressed through this action.

Having decided that it was necessary to pursue these claims to protect the County’s interests, the

County hired outside counsel to handle the litigation.39 The contract governing the County’s

representation in this litigation was approved by the Texas Comptroller of Public Accounts

pursuant to Tex. Gov’t Code § 403.0305.40

24. Defendants’ misconduct has placed an unreasonable burden on Angelina County’s

resources and ability to provide the public services and employee benefits it is obligated to and/or

39
See Resolution for approval of bringing suit on behalf of Angelina County, Texas, vs. various drug manufacturers,
developers, suppliers and others of a class of pharmaceutical class of drugs commonly referred to as opioids and
approval of Professional Services Agreement for Special Counsel attached hereto as Exhibit G  and Executed and
Approved Retention Agreement attached hereto as Exhibit H.
40
See Exhibit H.

PLAINTIFF’S ORIGINAL PETITION 9

has authority to provide to its residents and employees. Angelina County has the statutory duty

and/or authority to provide public safety and health services, including, but not limited to, the

following:

· Supporting paupers;41

· Providing county jails;42

· Providing health care in county jails;43

· Providing fire protection;44

· Enforcing drug laws;45

· Contracting with drug centers;46

· Commissioning drug education and counseling programs;47 and

· Paying county and precinct officers and employee compensation, office and
travel expenses, and any other allowances.48

25. Defendants’ misconduct − including Defendants’ calculated marketing campaign

of misinformation to physicians and patients − caused the damages to the County. They misled

physicians into overprescribing opioids, which directly created the need for dramatically increased

public services. The County relied on these misrepresentations in paying for its employees’

healthcare costs causing the County to incur increased healthcare costs for its own employees.

26. The harm caused by Defendants’ misconduct can be redressed by the Court in this

action. Defendants should be enjoined from continuing to manufacture, distribute, and sell opioids

in Angelina County without educating physicians and patients about the actual risks and benefits

41
Tex. Local Gov’t Code § 81.027.
42
Id. at § 351.001.
43
Id. at § 351.045.
44
Id. at § 352.001.
45
Id. at § 370.003.
46
Tex. Health & Safety Code at § 464.032.
47
Id. at § 465.001
48
Tex. Local Gov’t Code § 152.011. 

PLAINTIFF’S ORIGINAL PETITION 10

of its drugs. Furthermore, Defendants should compensate Angelina County for the funds it has

expended and continues to expend for medical insurance claims for opioids that were not medically

necessary, as well as increased costs of social services, health systems, law enforcement, the

judicial system, and treatment facilities.

IV. VENUE AND JURISDICTION

27. Venue is proper in Angelina County because all or a substantial part of the events or

omissions giving rise to this claim occurred in Angelina County. TEX. CIV. PRAC. & REM. CODE

§15.002(a)(2). This Court has subject-matter jurisdiction over this matter because Plaintiff’s damages

are in excess of the minimal jurisdictional limits of this Court. TEX. GOVT. CODE §24.007(b).

28. This Court has specific jurisdiction over all Defendants as their activities were

directed toward Texas, and injuries complained of herein resulted from their activities. Guardian

Royal Exchange Assur., Ltd. v. English China Clays, P.L.C., 815 S.W.2d 223, 227 (Tex. 1991).

Each Defendant has a substantial connection with Texas and the requisite minimum contacts with

Texas necessary to constitutionally permit the Court to exercise jurisdiction. See id. at 226.

V. PARTIES

A. Plaintiff

29. This action is brought for and on behalf of Angelina County, which provides a

wide range of services on behalf of its residents, including services for families and children,

public health, public assistance, law enforcement, and emergency care.

B. Defendants

30. PURDUE PHARMA L.P. is a limited partnership organized under the laws of

Delaware with its principal place of business in Stamford, Connecticut, and has at all times relevant

to this litigation, conducted business in this State. Said limited partnership is required to maintain

PLAINTIFF’S ORIGINAL PETITION 11

a registered agent for service of process but has not designated such an agent. Therefore, said

limited partnership may be served with process through the Secretary of State for the State of

Texas at its registered agent in Delaware, The Prentice-Hall Corporation System, Inc., 251 Little

Falls Drive, Wilmington, DE 19808, pursuant to the Texas Long-Arm Statute, Tex. Civ. Prac. &

Rem. Code §§ 17.041-.045. PURDUE PHARMA L.P. is, through its ownership structure, a Texas

resident. PURDUE PHARMA INC. is a New York corporation with its principal place of business

in Stamford, Connecticut, and has at all times relevant to this litigation, conducted business in this

State. Said corporation is required to maintain a registered agent for service of process but has not

designated such an agent. Therefore, said corporation may be served with process through the

Secretary of State for the State of Texas at its registered agent in Delaware, Corporation Service

Company, 80 State Street, Albany, NY 12207, pursuant to the Texas Long-Arm Statute, Tex. Civ.

Prac. & Rem. Code §§ 17.041-.045. THE PURDUE FREDERICK COMPANY is a Delaware

corporation with its principal place of business in Stamford, Connecticut, and has at all times

relevant to this litigation, conducted business in this State. Said corporation is required to maintain

a registered agent for service of process but has not designated such an agent. Therefore, said

corporation may be served with process through the Secretary of State for the State of Texas at its

registered agent in Delaware, The Prentice-Hall Corporation System, Inc., 251 Little Falls Drive,

Wilmington, DE 19808, pursuant to the Texas Long-Arm Statute, Tex. Civ. Prac. & Rem. Code

§§ 17.041-.045 (Purdue Pharma L.P., Purdue Pharma Inc., and The Purdue Frederick Company are

hereinafter referred to as “Purdue”).

31. Purdue manufactures, promotes, sells, and distributes opioids in the U.S. and

Angelina County. Purdue’s opioid drug, OxyContin, is one of the most addictive and abused

prescription drugs in American history. Purdue promotes opioids throughout the United States and

PLAINTIFF’S ORIGINAL PETITION 12

in Angelina County.

32. JANSSEN PHARMACEUTICALS, INC. is a Pennsylvania corporation with its

principal place of business in Titusville, New Jersey, and may be served through its registered

agent for service of process, CT Corporation System, 1999 Bryan Street, Suite 900, Dallas, TX

75201. JANSSEN PHARMACEUTICALS, INC. is a wholly owned subsidiary of JOHNSON &

JOHNSON. JOHNSON & JOHNSON (“J&J”) is a New Jersey corporation with its principal place

of business in New Brunswick, New Jersey, and has at all times relevant to this litigation conducted

business in this State. Said corporation is required to maintain a registered agent for service of

process but has not designated such an agent. Therefore, said corporation may be served with

process through the Secretary of State for the State of Texas at its corporate headquarters,

Attention: Legal Department, One Johnson & Johnson Plaza, New Brunswick, NJ 08933, pursuant

to the Texas Long-Arm Statute, Tex. Civ. Prac. & Rem. Code §§ 17.041-.045. ORTHO-MCNEIL-

JANSSEN PHARMACEUTICALS, INC., now known as JANSSEN PHARMACEUTICALS,

INC., is a Pennsylvania corporation with its principal place of business in Titusville, New Jersey,

and may be served through its registered agent for service of process, CT Corporation System,

1999 Bryan Street, Suite 900, Dallas, TX 75201. JANSSEN PHARMACEUTICA INC., now

known as JANSSEN PHARMACEUTICALS, INC., is a Pennsylvania corporation with its

principal place of business in Titusville, New Jersey, and may be served through its registered

agent for service of process, CT Corporation System, 1999 Bryan Street, Suite 900, Dallas, TX

75201. J&J is the only company that owns more than 10% of Janssen Pharmaceuticals’ stock, and

corresponds with the FDA regarding Janssen’s products. Upon information and belief, J&J

controls the sale and development of Janssen Pharmaceuticals’ drugs and Janssen’s profits inure

to J&J’s benefit (Janssen Pharmaceuticals, Inc., Ortho-McNeil-Janssen Pharmaceuticals, Inc.,

PLAINTIFF’S ORIGINAL PETITION 13

Janssen Pharmaceutica Inc., and J&J are hereinafter referred to as “Janssen”).

33. Janssen manufactures, promotes, sells, and distributes opioids in the U.S. and in

Angelina County.

34. ENDO HEALTH SOLUTIONS INC. is a Delaware corporation with its principal

place of business in Malvern, Pennsylvania, and has at all times relevant to this litigation conducted

business in this State. Said corporation is required to maintain a registered agent for service of

process but has not designated such an agent. Therefore, said corporation may be served with

process through the Secretary of State for the State of Texas at its registered agent in Delaware,

The Corporation Trust Company, Corporation Trust Center, 1209 Orange St., Wilmington, DE

19801, pursuant to the Texas Long-Arm Statute, Tex. Civ. Prac. & Rem. Code §§ 17.041-.045.

ENDO PHARMACEUTICALS, INC., a wholly-owned subsidiary of ENDO HEALTH

SOLUTIONS INC., is a Delaware corporation with its principal place of business in Malvern,

Pennsylvania, and may be served through its registered agent for service of process, CT

Corporation System, 1999 Bryan Street, Suite 900, Dallas, TX 75201 (Endo Health Solutions Inc.

and Endo Pharmaceuticals, Inc. are hereinafter referred to as “Endo”).

35. Endo develops, markets, and sells opioid drugs in the U.S. and in Angelina County.

Endo also manufactures and sells generic opioids in the U.S. and Angelina County, by itself and

through its subsidiary, Qualitest Pharmaceuticals, Inc.

36. The County lacks information sufficient to specifically identify the true names or

capacities, whether individual, corporate or otherwise, of Defendants sued herein under the

fictitious names DOES 1 through 100 inclusive. The County will amend this Petition to show their

true names and capacities if and when they are ascertained. Angelina County is informed and

believes, and on such information and belief alleges, that each of the Defendants named as a DOE

PLAINTIFF’S ORIGINAL PETITION 14

has engaged in conduct that contributed to cause events and occurrences alleged in this Petition

and, as such, shares liability for at least some part of the relief sought herein.

VI. FACTUAL ALLEGATIONS

37. Before the 1990s, generally accepted standards of medical practice dictated that

opioids should be used only for short-term acute pain – pain relating to recovery from surgery or

for cancer or palliative (end-of-life) care. Using opioids for chronic pain was discouraged or even

prohibited because there was a lack of evidence that opioids improved patients’ ability to

overcome pain and function. Instead the evidence demonstrated that patients developed tolerance

to opioids over time, which increased the risk of addiction and other side effects.

38. After the 1990s, Defendants dramatically changed doctors’ views regarding

opioids through a well-funded deceptive marketing scheme. Defendants were so successful that,

according to the National Safety Council, 74% of all doctors prescribe opioids for chronic back

pain and 55% prescribe opioids for dental pain, “neither of which is appropriate in most cases.”49

And 99% of doctors are prescribing them for longer than the three-day recommended period as

recommended by the CDC.50 Twenty-three percent prescribe at least a month’s worth of opioids

and evidence shows that just 30 days of usage can cause brain damage.51

39. Each Defendant used direct marketing and unbranded advertising (i.e., advertising

that promotes opioid use generally but does not name a specific opioid) disseminated by seemingly

independent third parties to spread false and deceptive statements about the risks and benefits of

long-term opioid use. Defendants advocated the widespread use of opioids for chronic pain even

49
National Safety Council, NSC Poll: 99% of Doctors Prescribe Highly-Addictive Opioids Longer than CDC
Recommends, 2017 (The NSC was founded in 1913 and chartered by Congress and is a non-profit organization
whose mission is to save lives by preventing injuries and deaths at work, in homes, and in the communities through
leadership, research, education, and advocacy).
50
National Safety Council, NSC Poll, supra.
51
National Safety Council, NSC Poll, supra.

PLAINTIFF’S ORIGINAL PETITION 15

though it contravened the “cardinal principles of medical intervention – that there be compelling

evidence of the benefit of a therapy prior to its large-scale use.”52

A. Defendants Used Multiple Avenues To Disseminate their False and Deceptive

Statements about Opioids.

40. Defendants spread their false and deceptive statements by (1) marketing their

branded opioids directly to doctors treating patients residing in Angelina County and the Angelina

County patients themselves and (2) deploying so-called unbiased and independent third parties to

Angelina County.

1. Defendants Spread and Continue to Spread Their False and Deceptive

Statements Through Direct Marketing of Their Branded Opioids.

41. Defendants’ direct marketing of opioids generally proceeded on two tracks. First,

each Defendant conducted advertising campaigns touting the purported benefits of their branded

drugs. For example, Purdue spent $200 million promoting and marketing OxyContin in various

forms.53 Defendants spent more than $14 million on medical journal advertising of opioids in 2011,

nearly triple what they spent in 2001, including $8.3 million by Purdue, $4.9 million by Janssen,

and $1.1 million by Endo.

42. A number of Defendants’ branded ads deceptively portrayed the benefits of opioids

for chronic pain. For example, Endo distributed and made available on its website,

www.opana.com, a pamphlet promoting Opana ER with photographs depicting patients with

physically demanding jobs like a construction worker and chef, implying that the drug would

provide long-term pain-relief and functional improvement.

43. Purdue also ran a series of ads, called “pain vignettes,” for OxyContin in 2012 in

medical journals. These ads featured chronic pain patients and recommended OxyContin for each.

52
Manchikanti, Ex. A, at 2.
53
Zee, Ex. B, at 2.

PLAINTIFF’S ORIGINAL PETITION 16

One ad described a “54-year-old writer with osteoarthritis of the hands” and implied that

OxyContin would help the writer work more effectively. Second, each Defendant promoted the

use of opioids for chronic pain through “detailers” – sales representatives who visited individual

doctors and medical staff in their offices – and small-group speaker programs.

44. Defendants devoted massive resources to direct sales contacts with doctors. In 2014

alone, Defendants spent $154 million on detailing branded opioids to doctors, including $108

million by Purdue, $34 million by Janssen, and $10 million by Endo.

45. Defendants sent their sales representatives to prescribers based on their specialties

and prescribing habits obtained from sales data through IMS Health. Defendants used this data to

monitor, and thereby target, specific physicians through the initial and renewal prescribing rates.

To ensure that their sales representatives were properly incentivized, Defendants motivated them

through bonuses. In 2001, Purdue paid $20 million in “sales incentive bonuses” to its sales

representatives.54

46. Defendants also utilized “influence mapping” to use decile rankings or similar

breakdowns to identify high-volume prescribers. The underlying strategy was that detailers would

have the biggest sales impact on high-volume prescribers. For example, Endo identified

prescribers representing 30% of its nationwide sales volume and planned sales visits three times

per month to these physicians. These detailers visited physicians across the nation, including

physicians in Angelina County. Defendants also had access to data from IMS Health, which

provides Defendants specific details about which medications physicians prescribe and how

frequently they do so. This data was collected from more than 50% of the pharmacies in the United

States, which would inform Defendants which doctors to target to convince them to prescribe more

54
Zee, Ex. B, at 2.

PLAINTIFF’S ORIGINAL PETITION 17

opioids or to start prescribing opioids instead of the medications they had been prescribing.

47. Another manner in which Defendants expanded their sales was to target prescribers

in individual zip codes and local boundaries. Defendants would send a detailer based on ease of

in-person access and the likelihood of convincing the physician to prescribe a higher number of

opioids and at higher doses.

48. As part and parcel of their detailing of opioids to physicians, Purdue trained its sales

representatives to inform physicians that the risk of addiction was “less than one percent” even

though studies demonstrated that there was a high incidence of drug abuse associated with

prescription opioid use for chronic pain.55

49. As Defendants’ marketing efforts grew, they targeted nurse practitioners and

physician assistants who, a 2012 Endo business plan noted, were “share acquisition” opportunities

because they were more responsive than physicians to details and wrote most of their prescriptions

without a physician consult.

50. Studies demonstrate that visits from sales representatives influence the prescribing

practices of residents and physicians by curtailing the prescription of generic drugs and rapidly

expanding the prescription of new drugs, such as opioids for chronic pain.56

51. Defendants also paid doctors to serve on speakers’ bureaus, to attend programs, and

for meals.57 In 2017, Dr. Hadland identified some of these payments from pharmaceutical

companies to physicians prescribing opioids.58 It was the first time “industry payments to

physicians related to opioid marketing” could be collated because of the “Open Payments program

55
Zee, Ex. B, at 3.
56
Zee, Ex. B, at 6.
57
See Scott E. Hadland, M.D., M.P.H, M.S., Industry Payments to Physicians for Opioid Products, 2013-2015, 107
Am. J of Pub. Health 9, Sept. 2017, attached hereto as Exhibit C.
58
Exhibit C at 1493.

PLAINTIFF’S ORIGINAL PETITION 18

database” authorized under the “Physician Payments Sunshine Act.”59 Dr. Hadland explained that

it was the first large-scale examination of these payments.60

52. One statistic Dr. Hadland gleaned from the data is that nearly 1 in 5 family

physicians in 2013, out of 108,971 active family physicians, received an opioid-related payment.61

After culling through the Open Payments program database, Dr. Hadland concluded that

“[f]inancial transfers” from pharmaceutical companies to physicians prescribing opioids “were

substantial and widespread and may be increasing in number and value.”62

53. Some of the financial transfers most likely involved speaker programs, which

provided: (1) an incentive for doctors to prescribe a particular opioid (so they might be selected to

promote the drug); (2) recognition and compensation for the doctors selected as speakers; and (3)

an opportunity to promote the drug through the speaker to his or her peers. These speakers gave

the false impression that they were providing unbiased and medically accurate presentations when

they were, in fact, presenting a script prepared by Defendants. On information and belief, these

presentations conveyed misleading information, omitted material information, and failed to correct

Defendants’ prior misrepresentations about the risks and benefits of opioids.

54. Defendants employed the same marketing plans, strategies, and messages in and

around Angelina County, Texas as they did nationwide. Across the pharmaceutical industry, “core

message” development is funded and overseen on a national basis by corporate headquarters. This

comprehensive approach ensures that Defendants’ messages are accurately and consistently

delivered across marketing channels and in each sales territory. Defendants consider this high level

of coordination and uniformity crucial to successfully marketing their drugs.

59
Exhibit C.
60
Id. at 1495.
61
Hadland, Ex. C, at 1494.
62
Id. at 1495.

PLAINTIFF’S ORIGINAL PETITION 19

 2. Defendants Used a Diverse Group of Seemingly Independent Third Parties
to Spread False and Deceptive Statements about the Risks and Benefits of
Opioids.

55. Defendants also deceptively marketed opioids in and around Angelina County

through unbranded advertising. This advertising was ostensibly created and disseminated by

independent third parties. But by funding, directing, reviewing, editing, and distributing this

unbranded advertising, Defendants controlled the deceptive messages disseminated by these third

parties and acted in concert with them to falsely and misleadingly promote opioids for treating

chronic pain. Unbranded advertising also avoided regulatory scrutiny because Defendants did not

have to submit it to the FDA, and therefore it was not reviewed by the FDA. But it is illegal for a

drug company to distribute materials that exclude contrary evidence or information about the

drug’s safety or efficacy that “clearly cannot be supported by the results of the study.”63 Moreover,

a drug company cannot compare or suggest that its “drug is safer or more effective than another

drug…when it has not been demonstrated to be safer or more effective in such particular by

substantial evidence of substantial clinical experience.”64 It is therefore Defendants’ responsibility

to ensure that not only is its label accurate and complete, but that any and all materials they

distribute is accurate and complete.65

56. Defendants’ deceptive unbranded marketing often contradicted their branded

materials. For example, Endo’s unbranded advertising contradicted its concurrent, branded

advertising for Opana ER:

63
21 C.F.R. § 99.101(a)(4).
64
21 C.F.R. § 202.1 (e)(6)(ii).
65
See 21 C.F.R. § 201.56 (providing general requirements for prescription drug labeling); 21 C.F.R.
§ 314.70(c)(6)(iii)(A-C) (providing for changes to labels that strengthen precautions, warnings, or adverse reactions,
as well as statements about drug abuse, dependence, or overdosage); see also Wyeth v. Levine, 555 U.S. 555 (2009)
(holding that a drug company bears responsibility for the content of its drug label at all times).

PLAINTIFF’S ORIGINAL PETITION 20

 Pain: Opioid Therapy Opana ER Advertisement
(Unbranded) (Branded)
“All patients treated with opioids
“People who take opioids as require careful monitoring for
prescribed usually do not signs of abuse and addiction, since
become addicted.” use of opioid analgesic products
carries the risk of addiction even
under appropriate medical use.”

57. Drug companies that make, market, and distribute opioids are generally subject to

rules requiring truthful marketing of prescription drugs. A drug company’s branded marketing,

which identifies and promotes a specific drug, must: (a) be consistent with its label and supported

by substantial scientific evidence; (b) not include false or misleading statements or material

omissions; and (c) fairly balance the drug’s benefits and risks.66

58. This framework ensures that drug companies, which are best suited to understand

the properties and effect of their drugs, bear the responsibility of providing accurate information

so that prescribers and users can assess the risks and benefits of the drugs.

59. Defendants did not follow this framework in assisting, creating, and/or distributing

third-party publications that included warnings and instructions either mandated by the FDA-

required drug labels or that described the risks and benefits known to Defendants. The publications

either failed to disclose the risk of addiction and misuse or affirmatively denied the risk of

addiction. The publications also “appeared” to be independent third-party materials that had the

effect of carrying more weight and credibility to convince physicians that opioids were safe for

chronic pain.

a. Defendants Utilized Treatment Guidelines to Promote their Deception.

60. Defendants used treatment guidelines to normalize the use of opioids for chronic

66
21 U.S.C. § 352(a); 21 C.F.R. §§ 1.21(a); 202.1(e)(3); 202.1(e)(6).

PLAINTIFF’S ORIGINAL PETITION 21

pain. Doctors, especially general practitioners and family doctors, rely upon treatment guidelines

when faced with patients complaining of chronic pain. Scientific literature references treatment

guidelines in making its conclusions and third-party payers use treatment guidelines to determine

coverage. Even Endo’s internal documents indicate that sales representatives discussed treatment

guidelines with doctors during individual sales visits.

1. The FSMB Wrote or Sponsored Misleading and Deceptive Guidelines.

61. Headquartered in Euless, Texas, the Federation of State Medical Boards (“FSMB”)

is a trade organization representing the various state medical boards in the United States. The state

boards that comprise the FSMB membership have the power to license doctors, investigate

complaints, and discipline doctors. The FSMB finances opioid and pain-specific programs through

grants from Defendants.

62. In 1998, the FSMB developed Model Guidelines for the Use of Controlled

Substances for the Treatment of Pain (“FSMB Guidelines”), which was produced in collaboration

with pharmaceutical companies. The FSMB guidelines instructed that opioids were “essential” for

the treatment of chronic pain, even as a first prescription option.

63. A book adapted from the 2007 FSMB guidelines, Responsible Opioid Prescribing:

A Physician’s Guide (“Opioid Prescribing”), released March 1, 2009 makes these same claims.

Opioid Prescribing was supported by a consortium of pharmaceutical companies and Front Groups

with an interest in ensuring that “effective” pain management included the use of opioids.

64. The author of Opioid Prescribing, Scott Fishman, M.D., chaired the board and was

past president of the American Pain Foundation and served as president of the American Academy

of Pain Medicine and served on the board of directors. Opioid Prescribing was sponsored by the

Alliance of State Pain Initiatives, Federation of State Medical Boards, and the University of

PLAINTIFF’S ORIGINAL PETITION 22

Wisconsin School of Medicine and Public Health.67

65. Dr. Fishman was a paid consultant to Cephalon and Eli Lilly. Dr. Fishman was also

a paid consultant, on the Speakers’ Bureau, and part of the research support for Endo, Merck,

Janssen, Pfizer and Purdue.68

66. Opioid Prescribing was designed for continued medical education (“CME”) in

which a physician had to read the book, complete questions, and fulfill administrative steps to

receive 7.5 hours of credit. The first page of Opioid Prescribing specifically states that opioids

are the “drugs of choice” and “essential in the treatment of persons with chronic non-cancer pain”

and that the CME will inform physicians about the laws and regulations governing the prescribing

of opioids for pain control.69 It also specifically teaches physicians how to protect their practices

from unwarranted federal scrutiny.70

67. Opioid Prescribing marketed “[o]pioid analgesics” as the “drugs of choice for the

management of moderate to severe pain . . . [which] may be essential in the treatment of persons

with chronic non-cancer pain.”71 The goal was to “change patient care, medical knowledge,

practice-based learning, interpersonal and communication skills, and professionalism . . . .”72 The

argument was that opioids were “underutilized” despite their “effectiveness.”73 The truth, known

to Dr. Fishman and Defendants herein, was that using opioids “for other than legitimate medical

purposes pose[d] a threat to the individual and society,” posed high risks for overdose and

addiction, and remained unproven as safe and effective for the long-term treatment of non-cancer

67
Scott M. Fishman, M.D., Responsible Opioid Prescribing, A Physician’s Guide, FSMB Foundation, Waterford
Life Sciences, 2009.
68
Id.
69
Id.
70
Id.
71
Fishman supra, at i.
72
Id.
73
Fishman supra.

PLAINTIFF’S ORIGINAL PETITION 23

pain.74

68. It was even conveyed to doctors that undertreating pain would be officially

disciplined whereas doctors prescribing opioids for chronic pain would not be disciplined. Opioid

Prescribing described a case in which a physician was sued for “elder abuse” and the jury awarded

$1.5 million to the plaintiff as an example of a physician that had been “successfully sued for not

treating pain aggressively.”75 Opioid Prescribing cautioned that “these legal precedents sound a

warning that there are risks associated with under-treating.”76 In actuality, it was a threat that

doctors would be punished if they failed to prescribe opioids to patients who complained about

pain. That teaching has held true given that according to the National Safety Council, 67% of

doctors prescribe opioids, in part, based on a patient’s expectations.77 Moreover, approximately

74% of doctors incorrectly believe morphine and oxycodone are the most effective ways to treat

pain even though research shows that over-the-counter medications such as ibuprofen and

acetaminophen are the most effective pain relief for acute pain.78

69. Defendants also allayed any concerns doctors may have about patients exhibiting

addictive behavior by highlighting the now debunked myth of “pseudoaddiction.” Dr. Fishman

described pseudoaddiction as a sign that patients were receiving an inadequate dose to obtain pain

relief, not as a sign that the patient was exhibiting drug-seeking or addictive behavior.79

70. Prescribing Opioids taught physicians that the following signs were evidence of

“pseudoaddiction” and not drug seeking behavior or signs of addiction so long as prescribing

additional opioids resolves the pain:

74
Fishman supra. at 6, 9.
75
Id. at 28.
76
Fishman, supra.
77
National Safety Council, supra.
78
National Safety Council, supra.
79
Fishman, supra, at 62.

PLAINTIFF’S ORIGINAL PETITION 24

 · Requesting analgesics by name;

· Demanding or manipulative behavior,

· Clock watching;

· Taking opioid drugs for an extended period;

· Obtaining opioid drugs from more than one physician; and

· Hoarding opioids.80

71. Indeed, the types of behaviors that Dr. Fishman posed as “MORE indicative of

addiction” included:

· Stealing money to obtain drugs;

· Performing sex for drugs;

· Stealing drugs from others;

· Prostituting others for money to obtain drugs;

· Prescription forgery; and

· Selling prescription drugs.81

72. Certainly by the time a patient is performing sex for drugs, the patient has long been

addicted and exhibited addictive behavior that was ignored by physicians at the explicit direction

of Defendants. This conclusion is supported by the American Psychiatric Association.

73. In the DSM-IV, addiction is “manifested” by three (or more) of the following in a

12-month period, including:

a) Tolerance described as:

A need for markedly increased amounts of the substance to achieve

intoxication or the desired effect

or

80
Fishman supra.
81
Fishman supra, at 63.

PLAINTIFF’S ORIGINAL PETITION 25

 Markedly diminished effect with continued use of the same amount of the
substance;

b) Withdrawal manifested by:

The characteristic withdrawal syndrome for the substance

or

The same (or closely related) substance is taken to relieve or avoid

withdrawal symptoms;

c) The substance is taken in larger amounts or over a longer period than

intended; and

d) Spending a great deal of time to obtain the substance, such as visiting

multiple doctors or driving long distances.82

74. According to Defendants, as seen in Prescribing Opioids and other publications,

signs of addiction as defined by the American Psychiatric Association are not signs of addiction,

but of pseudoaddiction that justifies taking more opioids for a longer period of time.

75. The reason not to discontinue the use of opioids – indeed, the foundation upon

which Defendants built its opioid empire – was “the undertreatment of pain.”83 Opioid Prescribing

claimed the undertreatment of pain has “been recognized as a public health crisis for decades. The

cost of human suffering is immeasurable. Turning away patients in pain simply is not an option.”84

However, according to Dr. Donald Treater, medical advisor at The National Safety Council:

“Opioids do not kill pain; they kill people.”85

76. Prescribing Opioids acknowledged that by 2005, more than 10 million Americans

were abusing prescription drugs, which is more than the combined number of people abusing

82
American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, Fourth Ed.,
Washington, D.C., American Psychiatric Assoc., 2000.
83
Fishman, supra, at 105.
84
Fishman, supra; see also id. at 80 (stating that efforts have been made to reduce the undertreatment or non-
treatment of pain in children, the elderly, and in other vulnerable patient populations).
85
National Safety Council, supra.

PLAINTIFF’S ORIGINAL PETITION 26

cocaine, heroin, hallucinogens, and inhalants combined.86 It also acknowledged that prescription

opioids are associated with more overdose deaths than cocaine and heroin combined.87 Yet the

book then cautioned that the “undertreatment” of non-cancer pain was a public health crisis of

equal importance that justified more opioid prescribing.

77. Under the guise of addressing “legitimate cause of undertreated pain” that “patients

and advocates have been pushing to address,”88 Defendants tailored opioid marketing campaigns

to affect children and the elderly. The Defendants made significant efforts to promote more opioid

prescribing for “untreated or undertreated pain in children, older patients, and in all other

vulnerable patient populations.”89

78. Defendants also taught physicians that “[p]ain is what the patient says it is” and that

a physician “cannot measure or even confirm the pain that a patient is experiencing.”90 As such,

“pain remains an untestable hypothesis.”91 Furthermore, “[p]atients should not be denied opioid

medications except in light of clear evidence that such medications are harmful to the patient.”92

All in all, opioids would cure the “pain epidemic” facing Americans. And yet, chronic pain

continues to be a problem facing Americans, as well as an opioid epidemic of addiction and death.

79. A total of 200,000 copies of Opioid Prescribing, which Dr. Fishman wrote for the

FSMB, has been delivered to U.S. prescribers through 20 state medical boards, including Texas.93

The FSMB earned approximately $250,000 from the sale. The FSMB website describes the book

as the “leading continuing medication education (CME) activity for prescribers of opioid

86
Responsible Opioid Prescribing, supra, at 6.
87
Id.; Prescribing Opioids even recognized that “[b]ehind these figures lie millions of individual stories of personal
tragedy: untimely death, fractures families, shattered dreams and wasted lives.” Id. at 7.
88
Id. at 8.
89
Fishman, supra, at 8.
90
Fishman supra, at 14.
91
Id. at 13.
92
Id. at 9.
93
Scott M. Fishman, M.D., Listening to Pain, Oxford Univ. Press, 2012, at 135.

PLAINTIFF’S ORIGINAL PETITION 27

medications.”

80. The guidelines for Opioid Prescribing were posted online for use and reliance by

physicians throughout America, including but not limited to, those servicing patients in Angelina

County. State medical boards even encouraged physicians to buy the book and participate in the

CME. The North Carolina Medical Board stated on its website that Prescribing Opioids “has been

widely used and supported in the medical and regulatory communities as the leading continuing

medical education (CME) activity for prescribers of opioid medications.”94 The website then

informs physicians that a CME accompanies the book and directs them to the book and how to

claim the CME. The FSMB also hosted free CMEs in Texas, including Houston, Dallas, and

Austin, related to extended-release and long-acting opioids.95 The CME taught physicians the “safe

and responsible prescribing of opioid medications and [was] aimed at improving prescriber

training and counseling for patients while providing more thorough information on extended-

release or long-acting (ER/LA) opioid products on the market.”96

81. The impact of Opioid Prescribing was even studied through a survey sent to 12,666

licensed Georgia physicians six weeks after receiving the book.97 The lead author was a member

of FSMB.98 A total of 508 physicians completed the online survey and of those, 82.1% rated the

book either “very good” or “good” for improving care for their patients in pain.99 Almost one-third

94
North Carolina Medical Board, FSMB Foundation Publishes Second Edition of Prescribing Book, Forum
Newsletter, July 31, 2012; see also University of Wisconsin School of Medicine and Public Health, Federation of
State Medical Boards, Responsible Opioid Prescribing – Book Helps Physicians Reduce Risk of Opioid Diversion
and Abuse, April 1, 2009 (describing the book and CME activity).
95
Texas Medical Board, Extended-Release and Long-Acting Opioid Analgesics Risk Evaluation and Mitigation
Strategy, www.tmb.state.tx.us.
96
Id.
97
A. Young, Physician Survey Examining the Impact of an Educational Tool for Responsible Opioid Prescribing, J.
Opioid Management, Mar-Apr. 2012.
98
Id.
99
Id.

PLAINTIFF’S ORIGINAL PETITION 28

(32.2%) claimed that they intended to make changes to their practice after reading the book.100 Of

note, 42.8% of solo practitioners and 41.6% of primary care providers were more likely to make

changes to their practice than doctors in other areas.101 Of the respondents, 57.7% said that the

book was better than others with regard to prescribing opioids and on pain management.102

82. Opioid Prescribing was therefore an effective tool that impacted specific doctors

and their prescribing practices, as concluded by the study. Specifically, the study provided “insight

into which physician population would be the most receptive to the type of information presented

in Dr. Fishman’s book” and that population was to “first target[] solo and primary care

physicians.”103 Defendants found out that their educational efforts “significantly altered

prescription practices.”104

2. The Joint Commission also Spread Deceptive Information.

83. The Joint Commission on Accreditation of Healthcare Organizations (“JCAHO”)

is a United States-based non-profit, tax-exempt organization that “accredits and certifies nearly

21,000 health care organizations and programs in the United States.”105 A majority of state

governments recognize accreditation from the Joint Commission as a condition of licensure and

for receiving Medicaid and Medicare reimbursements.106 CHI St. Luke’s Health Memorial System

in Lufkin, Texas, which is one of the main hospitals that feeds into Angelina County, is accredited

by and subscribes to the JCAHO.107

100
A. Young, supra.
101
Id.
102
Id.
103
Id.
104
A. Young, supra.
105
www.jointcommission.org.
106
Anthony Anonimo, Poppy Seed. Revealing the Roots of the Opioid Epidemic, Trinity Mother Frances Health
System, 2017, at 65.
107
www.jointcommission.org.

PLAINTIFF’S ORIGINAL PETITION 29

 84. According to the JCAHO, it “continuously improve[s] health care for the public”

and inspires health care organizations “to excel in providing safe and effective care of the highest

quality and value.”108 The JCAHO is not independent, but has been influenced by Defendants and

those Defendants used the JCAHO as a marketing shill to spread the misleading message that

opioids are non-addictive and safe as a first-line analgesic to treat any complaint of pain.

85. In 2000, the JCAHO published Pain Assessment and Management: An

Organizational Approach (“Pain Assessment”), which was paid for by Purdue and reviewed by

June L. Dahl, Ph.D., who has worked for Abbott, Endo, and Purdue.109

86. The JCAHO mission statement on the inside cover page of the book explains that

it aspires “to continuously improve the safety and quality of care provided to the public through

the provision of health care accreditation and related services that support the performance

improvement in health care organizations.”110 One of its big achievements, however, is its

endorsements of new pain management standards that underscored Defendants’ fraudulent

message.

87. JCAHO, with the help of the American Pain Society (“APS”), a Front Group,

loosened pain management standards thereby allowing doctors to prescribe opioids for any

complaint of pain. To that end, “[t]he Joint Commission recognize[d] pain as a major, yet largely

avoidable, problem . . . .[and] has expanded the scope of its pain management standards, which

have been endorsed by the American Pain Society (APS), to cover all pain scenarios in accredited

health care organizations rather than limiting the scope to end-of-life care.”111 (Emphasis

added.) On January 1, 2001, Texas incorporated JCAHO pain management standards for hospital

108
www.jointcommission.org.
109
Joint Commission on Accreditation of Healthcare Organizations, Pain Assessment and Management, 2000.
110
Pain Assessment, supra.
111
Pain Assessment, supra.

PLAINTIFF’S ORIGINAL PETITION 30

and healthcare group accreditation.112 The Texas Medical Association advertises that Pain

Assessment “provides practical help in integrating pain assessment and management into

organizational systems . . . .”113

88. Pain Assessment established the cornerstone of Defendants’ message that “all pain

scenarios” should be included in pain management practices.114 It explained that “[p]ain is the

most common reason individuals seek medical attention. According to the American Pain Society

(APS), 50 million Americans are partially or totally disabled by pain.”115 “The conclusion? Pain

is undertreated – despite the availability of effective pharmacologic and nonpharmacologic

therapies. Why?”116

89. The answer is on the first page of Pain Assessment. There is a chronic pain

epidemic. Chronic pain is undertreated. Chronic pain can be managed and even cured with opioids,

which are safe and effective, according to Pain Assessment. And the JCAHO encouraged

organizations to establish standards for recording and responding to patient pain reports and

monitoring staff performance and compliance with those standards, so that a physician who did

not agree with the JCAHO standards faced the specter of poor performance evaluations.117

90. According to Pain Assessment, the reasons healthcare professionals had not used

opioids previously included: (1) inadequate knowledge of opioids pharmacology and pain therapy,

(2) poor pain assessment practices, (3) unfounded concerns about regulatory oversight, and (4)

fear of opioids’ side effects such as tolerance and addiction.118

112
Texas Medical Association, JCAHO Pain Management Services, available at
https://www.texmed.org/Template.aspx?id=2389&terms=The%20war%20on%20pain.
113
Pain Assessment, supra.
114
Pain Assessment, supra, at p. 1.
115
Id.
116
Id.
117
Pain Assessment, supra, at 41-42.
118
Pain Assessment, supra.

PLAINTIFF’S ORIGINAL PETITION 31

 91. Pain Assessment asserted that few practitioners received adequate training in pain

management in medical school or during their residency resulting in the failure to prescribe opioids

or nonsteroidal anti-inflammatory drugs (NSAIDS) on a regular basis leaving patients without pain

relief.119 “[Many] health care professionals lack the knowledge and skills to manage pain

effectively, and they fear the effects of treatment.”120 Too few health care systems make pain

management a priority.121 Some clinicians had “inaccurate and exaggerated concerns about

addiction, tolerance, respiratory depression, and other opioid side effects, which lead them to be

extremely cautious about the use of drugs.”122 Instead of expanding upon and explaining the risks

of opioids, Pain Assessment states: “This attitude prevails despite the fact there is no evidence

that addiction is a signification issue when persons are given opioids for pain control.”123

(Emphasis added). That claim of insignificant addiction risk was false when made and remains

false today. Yet it worked as intended to mislead treating doctors, medical staff, and patients into

believing opioids could and should be utilized more often. Indeed, 74% of doctors “incorrectly

believe morphine and oxycodone” are the “most effective ways to treat pain” even though research

shows that over-the-counter pain relievers are the most effective for acute pain.124 Even worse,

20% of doctors prescribing opioids prescribed at least a month’s worth, even though the evidence

shows that “30-day use causes brain changes.”125

92. Patients also contributed to the pain epidemic by their reluctance to report their pain

and to take medications,126 according to Pain Assessment. Doctors were instructed to engage

119
Pain Assessment, supra.
120
Id. at 3.
121
Id. at 1.
122
Pain Assessment, supra, at 4.
123
Id.
124
National Safety Council, supra.
125
Pain Assessment, supra.
126
Pain Assessment, supra, at 4.

PLAINTIFF’S ORIGINAL PETITION 32

patients in conversations about their pain before prescribing opioids by: (1) asking for pain relief

when the pain begins; (2) helping the doctor or nurse assess the pain; and (3) telling the doctor or

nurse if the pain is not relieved.127 Doctors were taught that “[t]he single most reliable indicator of

the existence and intensity of pain is the individual’s self-report.”128 Indeed, the individual’s self-

report was to be the primary source of information for the doctor and deemed more reliable than

the observations of others.129

93. The bombardment of information, instruction, books, pamphlets, seminars, ads, and

marketing regarding this “pain epidemic” was so successful that pain has been included as the

“fifth vital sign” to be recorded along with the individual’s temperature, pulse, respiration, and

blood pressure.130 This strategy was first pitched by the APS to ensure that pain management

gained acceptance in the medical community, which it did.131

94. Beginning in 1999, the Veteran’s Health Administration began routinely assessing

pain as the fifth vital sign in every individual.132 And according to Pain Assessment, the research

showed that “when pain assessment information is included in clinical charts, those individuals’

analgesics [meaning opioids] are more likely to be increased.”133 In other words, including pain as

a fifth element results in not only the prescribing of more opioids, it results in the prescribing of

higher doses of opioids.

95. Pain Assessment also framed the role of key opinion leaders (“KOL”) as

trustworthy people “to evaluate new clinical information, assess new practices, and then determine

127
Pain Assessment, supra at 8.
128
Id. at 13.
129
Id.
130
Pain Assessment, supra, at 20.
131
Pain Assessment, supra at 20-21.
132
Id. at 21.
133
Pain Assessment, supra.

PLAINTIFF’S ORIGINAL PETITION 33

their value within the context of the local setting.”134 Doctors were expected to accept KOLs

opinions even though KOLs are not “necessarily innovators or authority figures.”135 KOLs

convinced practitioners that their current chronic pain treatment was “outdated, inappropriate,

unsupported by research evidence, or no longer accepted by colleagues.”136

96. Expert leaders, on the other hand, influenced and implemented protocols with

individuals or small groups.137 These “academic strategies” included “conducting interviews to

determine baseline knowledge, stimulating active participation during educational sessions, using

concise graphic educational materials, and highlighting or replicating essential messages.”138

Academic detailing was modeled after pharmaceutical detailing practices in which representatives

visited physicians to talk about specific medicines, just as Defendants’ representatives met with

physicians to about opioids.139 Simply put, Pain Assessment was a part of a marketing campaign

to plow ground for Defendants to sell more opioids, and the book set forth sophisticated, multi-

layered marketing strategies that were most effective in executing the campaign.

97. If a doctor was not available to prescribe opioids, a nurse would suffice. A nurse

specializing in oncology, surgery, critical care, or a nurse anesthetist, as well as a clinical

pharmacist, can “serv[e] as role models, provid[e] pain management education and consultation,

and act[s] as agents of change.”140 These educational efforts “significantly altered prescription

practices.”141

134
Pain Assessment, supra, at 24.
135
Id.
136
See id. at 25.
137
Id.
138
Pain Assessment, supra, at 25.
139
Pain Assessment, supra.
140
Pain Assessment, supra.
141
Id.

PLAINTIFF’S ORIGINAL PETITION 34

 98. To succeed in prescribing opioids for chronic pain, Defendants had to create a

market for chronic pain. To do so, Defendants literally encouraged patients not to tolerate pain and

to fear pain more than opioid addiction.142 Physicians and their staff were encouraged to educate

their patients about “effective pain management,” which included the use of opioids.143 Pain

Assessment explained research that showed Americans would rather bear pain because they were

afraid of “addiction, dependence on drugs, and tolerance to medications,” which affected not only

the patient’s willingness to report pain, but to use adequate amount of opioids to control the pain.144

A patient’s reluctance to take opioids out of fear they would not function normally meant that the

problem was “underreported” and the pain went “untreated.”145

99. Consequently, the answer was to inform and educate the patient that unrelieved

pain is harmful and that he or she should communicate pain.146 Pain Assessment instructed the use

of pain assessment instruments, including pain intensity scales, to describe the nature of the pain

and stressed that the “most reliable indicator of pain” was the individual’s self-report.147 Once the

patient reported the pain, the physicians and staff were taught to tell the patient about opioids,

explain that opioids were safe and effective, describe the name, dosage, and duration of the opioid

therapy, and explain the risk of pain versus the importance of pain management.148

100. To ensure that patients self-reported pain prior to hospital visits, Pain Assessment

encouraged health care systems to provide individuals and families with pain management

information prior to being admitted.149 And health care systems were told to leave individuals and

142
Pain Assessment, supra at 33.
143
Id.
144
Id.
145
Pain Assessment, supra, at 33.
146
Id. at 35.
147
Pain Assessment, supra.
148
Id.
149
Pain Assessment, supra at 36. 

PLAINTIFF’S ORIGINAL PETITION 35

family members with audio and videotapes to watch and listen to about the “importance” of “pain

relief” so that they truly understood the message – that is, if you have “pain,” tell us and we will

provide opioids.

101. The JCAHO was not independent and did not improve the safety or quality of

healthcare. Instead it was hijacked by Defendants to standardize pain management criteria that

required the use of opioids for chronic pain. The JCAHO was merely a pawn in the Defendants’

larger game.

102. Like other books and pamphlets used by Defendants to spread their “message,”

Pain Assessment was distributed throughout the nation and in Texas. As of today, anyone can buy

a used copy of Pain Assessment on Amazon.com for $26.48 plus $5.99 in shipping costs from a

seller in Texas.

b. Key Opinion Leaders (KOLs) were another Means of Disseminating False

Information.

103. Defendants also sponsored KOLs, a small circle of doctors who, upon information

and belief, were selected, funded, and elevated by Defendants because they publicly supported

dispensing opioids more widely and indiscriminately.

104. Defendants paid KOLs to serve as consultants or to appear on their advisory boards

and to give talks or present CMEs, and Defendants’ support helped these KOLs become respected

industry experts. As they rose to prominence, these KOLs promoted the benefits of opioids to treat

chronic non-cancer pain, repaying Defendants by advancing their marketing goals.

105. KOLs wrote articles and books, gave speeches, and taught CMEs to promote the

utilization of opioids to treat moderate non-cancer pain. Defendants created opportunities for

KOLs to participate in “studies” and write papers for the purpose of advancing Defendants’

marketing theme: opioids should be dispensed regularly and perpetually to treat a broad array of

PLAINTIFF’S ORIGINAL PETITION 36

pain complaints.

106. Defendants’ KOLs also served on committees that developed treatment guidelines

that strongly encourage using opioids to treat chronic pain, and on the boards of pro-opioid

advocacy groups and professional societies that develop, select, and present CMEs. Defendants

were able to direct and exert control over each of these activities through their KOLs.

107. Pro-opioid doctors are one of the most important avenues that Defendants use to

spread their false and deceptive statements about the risks and benefits of long-term opioid use.

Defendants know that doctors rely heavily and less critically on their peers for guidance, and KOLs

provide the false appearance of unbiased and reliable support for using opioids for chronic pain.

108. Different Defendants utilized many of the same KOLs. Two of the most prominent

are described below.

1. Russell Portenoy

109. Dr. Russell Portenoy, former Chairman of the Department of Pain Medicine and

Palliative Care at Beth Israel Medical Center in New York, is one example of a KOL who

Defendants identified and promoted to further their marketing campaign. Dr. Portenoy received

research support, consulting fees, and honoraria from Endo, Janssen, and Purdue (among others),

and was a paid consultant to Purdue.

110. Dr. Portenoy was instrumental in opening the door for the regular use of opioids to

treat chronic pain. He served on the American Pain Society (“APS”)/American Academy of Pain

Medicine (“AAPM”) Guidelines Committees, which endorsed the use of opioids to treat chronic

pain, first in 1997 and again in 2009. He was also a member of the board of the American Pain

Foundation (“APF”), an advocacy organization almost entirely funded by Defendants.

PLAINTIFF’S ORIGINAL PETITION 37

 111. Dr. Portenoy also made frequent media appearances promoting opioids. He

appeared on Good Morning America in 2010 to discuss using opioids long-term to treat chronic

pain. On this widely-watched program, broadcast in Texas and across the country, Dr. Portenoy

claimed: “Addiction, when treating pain, is distinctly uncommon. If a person does not have a

history, a personal history, of substance abuse, and does not have a history in the family of

substance abuse, and does not have a very major psychiatric disorder, most doctors can feel very

assured that that person is not going to become addicted.”150

112. Perhaps realizing that “[m]ore than 16,000 people die from opioid overdoses every

year,” Dr. Portenoy is now having “second thoughts” about the “wider prescription” of drugs like

Vicodin, OxyContin, and Percocet.151 Dr. Portenoy later admitted in a 2010 videotaped interview

that he “gave innumerable lectures in the late 1980s and ‘90s about addiction that weren’t true.”152

According to Dr. Portenoy, because the primary goal was to “destigmatize” opioids, he and other

doctors promoting them overstated their benefits and glossed over their risks.

113. Dr. Portenoy put doctors’ fear that opioids were dangerous and addictive, and

meant only for cancer patients, to rest by arguing that they could be taken safely for months, even

years, by patients with chronic pain.153 Dr. Portenoy, as well as other doctors making the speaker

rounds, asserted that “[l]ess than 1% of opioid users became addicted, the drugs were easy to

discontinue and overdoses were extremely rare in pain patients.”154

114. Dr. Portenoy also conceded that “[d]ata about the effectiveness of opioids does not

exist.”155 Dr. Portenoy candidly stated: “Did I teach about pain management, specifically about

150
Good Morning America television broadcast, ABC News, Aug. 30, 2010.
151
Thomas Catan & Evan Perez, A Pain-Drug Champion Has Second Thoughts, WALL ST. J., Dec.
17, 2012, attached hereto as Exhibit D.
152
Id.
153
Catan, supra.
154
Catan, supra.
155
Catan, supra.

PLAINTIFF’S ORIGINAL PETITION 38

opioid therapy, in a way that reflects misinformation? Well…I guess I did.”156

115. Before his moment of clarity, Dr. Portenoy co-authored a guide to publicize the

benefits of opioids for chronic pain, which was paid for by an unrestricted education grant from

Endo, titled A Clinical Guide to Opioid Analgesia (“Opioid Analgesia”).157 Opioid Analgesia

reiterated that opioids are “absolutely necessary” for pain relief.158

116. Although Opioid Analgesia claimed “to help clinicians make practical sense of the

varied and often conflicting pharmacologic, clinical and regulatory issues to promote the most

healthful outcomes possible for patients in pain,”159 the reality was that it expressed regret that

federal and state governments had passed controlled substances acts to stem addiction, which had

curtailed the prescription of opioids.160 This regulation, explained Opioid Analgesia, “contributed

to the underuse of opioid medications.”161

117. As with all other books, guidelines, and CMEs promoted by Front Groups and

KOLs, Opioid Analgesia establishes the absolute need for opioids in light of the chronic pain

epidemic. “Because pain is inherently subjective, patient self-report is the ‘gold standard’ for

assessment.”162 If there’s no discernible reason for the pain, then it should be characterized as

“idiopathic.”163 Regardless of how the pain is characterized, the solution, per Opioid Analgesia, is

opioids.

118. “While opioid analgesics are controlled substances, they are also essential

medication and are absolutely necessary for relief of pain.”164 “Opioid analgesics should be

156
Catan, supra.
157
Perry G. Fine, M.D. and Russell K. Portenoy, M.D., A Clinical Guide to Opioid Analgesia, McGraw-Hill, 2004.
158
Id. at 2.
159
Id. at 3.
160
Id.
161
Id. at 6.
162
Fine, supra, at 34.
163
Fine, supra, at 35.
164
Id. at Table 1.

PLAINTIFF’S ORIGINAL PETITION 39

accessible to all patients who need them for relief of pain.”165 Brushing away any concerns about

addiction, Opioid Analgesia posits that “[a] patient who has reached middle age without

developing compulsive use behaviors to potentially abusable drugs, including alcohol and nicotine,

appears to be at a very low risk” of addiction, especially if “there is no family history of

addiction.”166

119. Underplaying the risks of addiction, Opioid Analgesia falsely claimed that

“[o]verall, the literature provides evidence that the outcomes of the drug abuse and addiction are

rare among patients who receive opioids for a short period (i.e., for acute pain) and among those

with no history of abuse who receive long-term therapy for medical indications.”167 Even while

admitting there is “very little information about the risks of misuse, abuse, or addiction among

different opioid-treated populations” and even admitting the “[w]hen misused, opioids pose a

threat to society,”168 Defendants’ intentionally marketed opioids as effective and safe for treatment

of chronic pain and summed up the risk of addiction for short-term therapy as “rare.”169

120. Of course when addiction is as narrowly defined as it is in the books, CMEs, and

guidelines that Defendants publishes, the risk of addiction would be termed as “rare.” The

behaviors cited in Opioid Analgesia as “probably more suggestive” of addiction included:

· Selling prescription drugs;

· Forging prescriptions;

· Stealing or “borrowing” drugs from others;

· Injecting or inhaling (snorting, smoking) oral formulations; and

165
Fine, supra.
166
Id. at 21.
167
Id.
168
Id. at 31, 2.
169
Fine, supra, at 34.

PLAINTIFF’S ORIGINAL PETITION 40

 · Obtaining the prescription drugs from nonmedical sources.170

121. Whereas the following behaviors are “probably less suggestive” of addiction:

· Aggressive complaining about the need for more drug;

· Drug hoarding during periods of reduced symptoms;

· Requesting specific drugs; and

· Using the drug, without approval, to treat another symptom.171

122. Instead of these behaviors being symptoms of possible addiction, Dr. Portenoy

terms these behaviors as a “phenomenon” termed “pseudoaddiction.”172 Pseudoaddiction allows

physicians to discount these behaviors because “they are driven by desperation surrounding

unrelieved pain” and are “eliminated by measures that relieve the pain, such as an increase in

medication.”173 Instead of treating the “less suggestive” symptoms for what they are – signs of

addiction.

123. Opioid Analgesic was a success for Defendants in that it has been and continues to

be used extensively in CMEs, pamphlets, and reading lists for physicians looking for information

regarding opioids. For example, Opioid Analgesia was cited just last year in a presentation at the

University of North Texas College of Pharmacy on April 28, 2017, entitled Adverse Drug Events

Associated with Opiate-Based Pain Management (Emphasis added). It has also been listed as a

reference for a CME entitled The Management of Opioid-Induced Constipation published by the

University of North Texas Health Science Center, which was valid for CME from May 2009 to

May 2010. Finally, the book was included in the suggested reading list for a seminar entitled When

Opioids Are Indicated for Chronic Pain presented on March 26, 2011, in Houston, Texas.

170
Fine, supra, at 85.
171
Id.
172
Id. at 35.
173
Id. 

PLAINTIFF’S ORIGINAL PETITION 41

 2. Lynn Webster

124. Another KOL, Dr. Lynn Webster, was the co-founder and Chief Medical Director

of Lifetree Clinical Research, an otherwise-unknown pain clinic in Salt Lake City, Utah. Dr.

Webster was President in 2013 and is a current board member of AAPM, a Front Group that

ardently supports using opioids for chronic pain. He is a Senior Editor of Pain Medicine, the same

journal that published Endo special advertising supplements recommending Opana ER. Dr.

Webster authored numerous CMEs sponsored by Endo and Purdue while he was receiving

significant funding from Defendants.

125. In 2011, Dr. Webster presented a program via webinar sponsored by Purdue titled

Managing Patient’s Opioid Use: Balancing the Need and the Risk. Dr. Webster recommended

using risk screening tools, such as urine testing and patient agreements as a way to prevent “overuse

of prescriptions” and “overdose deaths,” which was available to and was intended to reach doctors

treating Angelina County residents.

126. Dr. Webster also was a leading proponent of the concept of “pseudoaddiction,” the

notion that addictive behaviors should be seen not as warnings, but as indications of undertreated

pain. In Dr. Webster’s description, the only way to differentiate the two was to increase a patient’s

dose of opioids. As he and his co-author wrote in a book entitled Avoiding Opioid Abuse While

Managing Pain (2007), a book that is still available online, when faced with signs of aberrant

behavior, increasing the dose “in most cases . . . should be the clinician’s first response.” Endo

distributed this book to doctors.

127. Years later, Dr. Webster reversed himself, acknowledging that “[pseudoaddiction]

obviously became too much of an excuse to give patients more medication.”174 Dr. Webster also

174
John Fauber & Ellen Gabler, Networking Fuels Painkiller Boom, MILWAUKEE WISC. J. SENTINEL, Feb. 19, 2012.

PLAINTIFF’S ORIGINAL PETITION 42

admits that “[i]t’s obviously crazy to think that only 1% of the population is at risk for opioid

addiction.”175

c. Front Groups Affirmed Defendants’ Falsities.

128. Defendants entered into arrangements with seemingly unbiased and independent

patient and professional organizations to promote opioids for treating chronic pain. Under

Defendants’ direction and control, these “Front Groups” generated treatment guidelines, unbranded

materials, and programs that favored using opioids for chronic non-cancer pain. They also assisted

Defendants by responding to negative articles, by advocating against regulatory changes that

would limit prescribing opioids in accordance with the scientific evidence, and by conducting

outreach to vulnerable patient populations targeted by Defendants.

129. These Front Groups depended on Defendants for funding and, in some cases, for

survival. Defendants also exercised control over programs and materials created by these groups

by collaborating on, editing, and approving their content, and by funding their dissemination. In

doing so, Defendants made sure these Front Groups would generate only the messages Defendants

wanted to distribute. Even so, the Front Groups held themselves out as independent and as serving

the needs of their members – whether patients suffering from pain or doctors treating those patients.

130. Defendants Endo, Janssen, and Purdue utilized many Front Groups, including many

of the same ones. Several of the most prominent are described below, but there are many others,

including the American Pain Society (“APS”), American Geriatrics Society (“AGS”), the

Federation of State Medical Boards (“FSMB”), American Chronic Pain Association (“ACPA”),

American Society of Pain Education (“ASPE”), National Pain Foundation (“NPF”) and Pain &

Policy Studies Group (“PPSG”).

175
Thomas Catan & Evan Perez, A Pain-Drug Champion Has Second Thoughts, WALL ST. J., Dec.17, 2012.

PLAINTIFF’S ORIGINAL PETITION 43

 1. American Pain Foundation (“APF”)

131. APF was founded in 1997 and professed to be an independent non-profit 501(c)3

organization “serving people with pain through information, advocacy and support.”176 It had a

membership of “close to 100,000 and growing” in 2010 and claimed to be the “largest advocacy

group for people with pain.”177 The APF lauded its participation in “close to 100 policy activities,”

which included testifying at legislative hearings to securing state and local proclamations for Pain

Awareness Month.178

132. APF, however, as the most prominent of Defendants’ Front Groups, received more

than $10 million in funding from opioid manufacturers from 2007 until it closed its doors in May

2012. Endo alone provided more than half that funding; Purdue was next at $1.7 million. Despite

the influx of funds from pharmaceutical companies, APF claimed to be an independent patient

advocacy group.

133. In 2009 and 2010, more than 80% of APF’s operating budget came from

pharmaceutical industry sources. Including industry grants for specific projects, APF received

about $2.3 million from industry sources out of total income of about $2.85 million in 2009. In

2010, Endo paid APF more than $1 million and Purdue paid APF between $1 million and 4.9

million.179 By 2011, APF was entirely dependent on incoming grants from Purdue, Endo, and

others to avoid using its line of credit. One of its board members, Russell Portenoy, explained the

lack of funding diversity was one of the biggest problems at APF.

176
American Pain Foundation, Treatment Options: A Guide for People Living with Pain, www.painfoundation.org;
see also 2010 Annual Report, American Pain Foundation.
177
2010 Annual Report, supra.
178
Id.
179
2010 Annual Report, supra.

PLAINTIFF’S ORIGINAL PETITION 44

 134. APF issued education guides for patients, reporters, and policymakers that

recommended opioids for chronic pain while trivializing their risks, particularly the risk of

addiction. Its Pain Community News, an “esteemed” quarterly newsletter, had a print circulation

of more than 68,000 plus additional online readers.180 Its monthly electronic newsletter, Pain

Monitor, was a monthly newsletter that provided links to pain-related news and research.181 The

APF also provided “patient representatives” for Defendants’ promotional activities, including

Purdue’s Partners Against Pain182 and Janssen’s Let’s Talk Pain.183

135. In one of its publications, Treatment Options: A Guide for People Living with Pain,

(“Treatment Options”), APF recognized contributions from Cephalon and Purdue.184 Treatment

Options was reviewed by Scott Fishman, M.D., Vice Chairman of the APF Board of Directors, and

Russell Portenoy, M.D., a Member of the APF Board of Directors and also a KOL.185 Treatment

Options set the stage for prescribing opioids by explaining their underuse despite their benefits.186

It dismissed the risk of addiction with the rhetoric that physical dependence was nothing more than

symptoms or signs of withdrawal that occurred when opioids were stopped suddenly or the dose

lowered too quickly.187

136. Responsible Opioid Prescribing and The War on Pain both had a tremendous

impact on doctors’ prescribing habits. In 2000, Scott Fishman, M.D., who served on APF’s board,

co-authored The War on Pain (“Pain War”) as general authoritative information about pain

180
2010 Annual Report, supra at 2.
181
Id. at 2.
182
In its “Partner against Pain” website, Purdue claimed that the risk of addiction from the use of OxyContin in
treating “chronic non-cancer pain” was “extremely small”; see also Zee, Ex. B, at 3.
183
Let’s Talk Pain was a “coalition effort that focus[ed] on supporting positive patient-provided communications”
regarding pain.
184
Treatment Options, supra, at ii.
185
Id. at iv.
186
Treatment Options, supra, at 11.
187
Id. at 14 (referring to symptoms such as sweating, rapid heart rate, nausea, diarrhea, goosebumps, and anxiety).

PLAINTIFF’S ORIGINAL PETITION 45

medicine.”188

137. Pain War seeks new specialties in which opioids can be prescribed for chronic pain.

Rheumatologists treating arthritis have been overlooked because they were more prone to

prescribe NSAIDS instead of opioids, such as morphine.189 But such “outdated ideas about

addiction and concerns about social stigmas” need to evolve because opioids offer “substantial

relief” with “less severe long-term side effects than chronic anti-inflammatories.”190

138. Pain War advocates for physical dependence to opioids, and equates withdrawal

symptoms from opioid drugs to that of cessation of coffee drinking. A “pain patient who is

dependent on opioids finds life restored,” the book advises, and then explains that removing a

patient from opioids causes physical, not psychological, consequences, like quitting coffee.191

Addiction to opioids is treated as a “phobia” or “notion” that “using opioids” are “always

addictive.”192

139. Pain War censures the failure to prescribe opioids and even suggests that such

failure is a criticism of the patient. For example:

Doses tend to be too low, the right narcotic preparation tends to be avoided, and the
prescribing period is often too short. Medicine’s reluctance to use appropriate doses
of opioid drugs gives patients the wrong message – their pain isn’t that important,
they are not trustworthy, they may be addicts, they are bad people if they take drugs
even if they are prescribed.193

140. Pain War was distributed across the nation, and sold in Texas, as evidence by a

seller from Texas offering the used book for $9.56 plus $5.99 in shipping costs on Amazon.com.

188
Scott Fishman, M.D., with Lisa Berger, The War on Pain, First Quill, 1st ed., 2000.
189
Id. at 154.
190
Fishman, War on Pain, supra, at 155.
191
Id. at 187.
192
Id. at 185.
193
Fishman, War on Pain, supra.

PLAINTIFF’S ORIGINAL PETITION 46

 141. As late as 2008, the APF was still relaying the same message. In A Reporter’s

Guide: Covering Pain and Its Management (“Reporter’s Guide”), the APF extolled that “[t]he

person with pain is the authority on the existence and severity of his/her pain. The self-report is

[the] most reliable indicator.”194 The Reporter’s Guide referred to pain as a health crisis and

concluded that it affected more Americans than “diabetes, heart disease and cancer combined.”195

142. Yet APF, Defendants’ Front Group also admitted that:

· 71% of people abusing prescription pain relievers received them from a friend
or family member without a prescription;

· Approximately 2.2 million Americans abused pain medication for the first time
in 2006; and

· Between 1992 and 2002, reported abuse by teenagers increased by 542%.196

143. Even though Defendants knew about the risks involved in prescribing opioids or

ingesting opioids, they continued to disseminate a story about a “pain epidemic” that could be

treated only through the use of opioids. Even a 542% increase in abuse by teenagers in the United

States in the span of ten years did not make Defendants change their marketing strategy or otherwise

modify their educational or promotional materials concerning the risks associated with the use of

opioids.

144. In addition to these publications, APF also engaged in a significant multimedia

campaign – through radio, television, and the internet – to educate patients about their “right” to

pain treatment, namely opioids. APF’s local and national media efforts resulted in 1,600 media

stories on pain in 2010, which was an increase of 1,255% from 2009.197 APF surmised that it

194
American Pain Foundation, A Reporter’s Guide: Covering Pain and Its Management, Oct. 2008, at 1, attached
hereto as Exhibit E.
195
Id. at 29.
196
Reporter’s Guide, Ex. E, at 29.
197
Reporter’s Guide, supra, at 15.

PLAINTIFF’S ORIGINAL PETITION 47

reached more than 600 million people with information and education related to pain.198 All of the

programs and materials were available nationally and were intended to reach patients and

consumers in Angelina County.

145. APF’s website was visited by nearly 275,000 people in 2010 and a National Pain

Foundation was expected to be complete in 2011.199 In May 2012, the U.S. Senate Finance

Committee began investigating the financial ties between Front Groups and trade organizations,

such as APF and the FSMB, and the opioid manufacturers. This investigation not only caused

damage to APF’s credibility but caused Defendants to cease its funding.

146. The Senate Finance Committee intended to investigate whether pharmaceutical

companies were responsible for the opioid epidemic by “promoting misleading information about

the drugs’ safety and effectiveness.”200 The Senate Finance Committee was concerned that a

“network of national organizations and researchers with financial connections to the makers of

narcotic painkillers . . . helped create a body of dubious information ‘favoring opioids’ that can be

found in prescribing guidelines, patient literature, position statements, books and doctor education

courses.”201

147. The Senate Finance Committee was especially concerned that “[a]mong the FSMB’s

educational initiatives has been the development and distribution of a guidebook intended to help

physicians recognize the risk of opioids and follow responsible and safe prescribing standards.”202

(Emphasis in original.) Hence, Dr. Fishman and his book Opioid Prescribing: A Physician’s Guide,

the first edition of which was released in 2007 and later accredited by the University of Wisconsin

198
Reporter’s Guide, supra.
199
2010 Annual Budget, supra, at 6
200
See Letter to Dr. Humayun J. Chaudhy dated May 8, 2012 from Charles E. Grassley and Max Baucus, at p. 2.
201
Id. quoting Milwaukee Journal Sentinel/MedPage Today, Follow the Money: Pain, Policy, and Profit, Feb. 19,
2012, available at at http://medpagetoday.com/Neurology/PainManagement/31256.
202
Chaudhy Letter, supra, at 5.

PLAINTIFF’S ORIGINAL PETITION 48

School of Medicine and Public Health, was at the center of the investigation.203

148. The Senate Finance Committee asked for any grants or financial transfers used to

produce the book, the revenue generated from the sale of the book, each state that distributed the

book, and the names of any people or organization involved in writing or editing the book.204

149. Within days, APF’s board voted to dissolve the organization and it ceased to exist.

The FSMB responded to the Senate Finance Committee’s inquiry, however, and agreed that “the

abuse and misuse of opioids is a serious national problem.”205 Dr. Chaudhy, speaking on behalf of

the FSMB, acknowledged that “prescription drug abuse and related deaths has grown at an alarming

pace in the United States.”206 Dr. Chaudhy described Dr. Fishman, the author of Opioid Prescribing,

as “one of the nation’s leading experts in pain medicine.”207

150. Opioid Prescribing was released from 2007 through January 2012, was distributed

in each of the 50 states, including Texas, and supported in the medical community as an educational

resource for doctors.208 The book is still being sold today. For example, a used copy of the book is

being sold on Amazon.com by Delta River Books, located in Texas, for $51.49 plus $3.99 in

shipping. Dr. Fishman also toured and gave keynote speeches about Opioid Prescribing. For

example, Dr. Fishman presented the keynote at the Federation of State Medical Board Meeting in

Fort Worth, Texas on April 28, 2012, which lasted three days.209 The book was also used

extensively by state regulators to make safe and responsible decisions about prescribing opioids.210

203
Chaudhy Letter, supra.
204
Id. at 3.
205
Letter to Max Baucus and Charles Grassley dated June 8, 2012 from Humayun J. Chaudhy, DO, FACP, at 1.
206
Chaudhy Letter, supra, at 1.
207
Id. at 5.
208
Id.
209
U.C. Davis, Fishman Gives Keynote at Federation of State Medical Boards Meeting, May 1, 2012, available at
https://ucdmc.ucdavis.edu/publish/news/newsroom/6523.
210
Chaudhy, supra, at 5, 17.

PLAINTIFF’S ORIGINAL PETITION 49

 151. As described herein, Dr. Fishman and his book was partly funded by Endo, Purdue,

and Abbott among others as evidenced in the response. In 2004, Purdue paid $87,895 in the form

of a grant to the FSMB to update the FSMB Model Guidelines for the Use of Controlled Substances

in the Treatment of Pain, along with other objectives related to opioids.211 In 2005, Purdue paid

$244,000 to FSMB and in 2006, Purdue paid $207,000 to FSMB for the continuation of the same

project.212 In 2008, Endo and Purdue each paid $100,000 in the form of a grant for the distribution

of Responsible Opioid Prescribing.213 Thus, from 2000-2012, Purdue paid $734,505.06 and Endo

paid $411,620.00 to the FSMB and FSMB Foundation.

152. Dr. Chaudhy’s response merely underscored Defendants’ role, through KOLs and

Front Groups, in controlling the message these groups conveyed about opioids.

2. American Academy of Pain Medicine (“AAPM”)

153. The American Academy of Pain Medicine, with Defendants’ assistance, prompting,

involvement, and funding, issued treatment guidelines and sponsored and hosted medical

education programs essential to Defendants’ deceptive marketing of chronic opioid therapy.

154. AAPM received over $2.2 million in funding since 2009 from opioid

manufacturers. AAPM maintained a corporate relations council, whose members paid $25,000 per

year (on top of other funding) to participate. The benefits included allowing members to present

educational programs at off-site dinner symposia in connection with AAPM’s marquee event – its

annual meeting held in Palm Springs, California, or other resort locations. AAPM describes the

annual event as an “exclusive venue” for offering education programs to doctors. Membership in

the corporate relations council also allows drug company executives and marketing staff to meet

211
Chaudhy Letter, supra, at 11.
212
Id. at 11-12.
213
Id. at 12.

PLAINTIFF’S ORIGINAL PETITION 50

with AAPM executive committee members in small settings. Defendants Endo, and Purdue were

members of the council and presented deceptive programs to doctors who attended this annual

event.

155. AAPM is viewed internally by Endo as “industry friendly,” with Endo advisors and

speakers among its active members. Endo attended AAPM conferences, funded its CMEs, and

distributed its publications. The conferences sponsored by AAPM heavily emphasized sessions

on opioids – 37 out of roughly 40 at one conference alone. AAPM’s presidents have included top

industry-supported KOLs Perry Fine, Russell Portenoy, and Lynn Webster. Dr. Webster was even

elected president of AAPM while under a DEA investigation. Another past AAPM president, Dr.

Scott Fishman, stated that he would place the organization “at the forefront” of teaching that “the

risks of addiction are . . . small and can be managed.”214

156. Defendants influenced AAPM through both their significant and regular funding

and the leadership of pro-opioid KOLs within the organization. AAPM’s staff understood they and

their industry funders were engaged in a common task – propagate a “pain epidemic” and solve it

by teaching that opioids were safe and effective for treating chronic pain.

157. In 1997, AAPM and the American Pain Society jointly issued a consensus

statement, The Use of Opioids for the Treatment of Chronic Pain, which endorsed opioids to treat

chronic pain and claimed there was a low risk that patients would become addicted to opioids. The

co-author of the statement, Dr. Haddox, was a paid speaker for Purdue at the time. Dr. Portenoy,

Defendants’ KOL, was the sole consultant. The consensus statement remained on AAPM’s

website until 2011.

214
Interview by Paula Moyer with Scott M. Fishman, M.D., Professor of Anesthesiology and Pain Medicine, Chief
of the Division of Pain Medicine, Univ. of Cal., Davis (2005), available at
http://www.medscape.org/viewarticle/500829.

PLAINTIFF’S ORIGINAL PETITION 51

 158. AAPM and APS issued their own guidelines in 2009 (“AAPM/APS Guidelines”)

and continued to recommend using opioids to treat chronic pain. Fourteen of the 21 panel members

who drafted the AAPM/APS Guidelines, including KOLs Dr. Portenoy and Dr. Perry Fine of the

University of Utah, received support from Janssen, Endo, and Purdue.

159. The 2009 Guidelines promote opioids as “safe and effective” for treating chronic

pain, despite acknowledging limited evidence, and conclude that the risk of addiction is

manageable for patients regardless of past abuse histories. One panel member, Dr. Joel Saper,

Clinical Professor of Neurology at Michigan State University and founder of the Michigan

Headache & Neurological Institute, resigned from the panel because he was concerned the 2009

Guidelines were influenced by contributions that drug companies, including Defendants, made to

the sponsoring organizations and committee members. These AAPM/APS Guidelines have been

a particularly effective channel of deception and have influenced not only treating physicians, but

also the body of scientific evidence on opioids. The Guidelines have been cited 732 times in

academic literature, were disseminated in and around Angelina County during the relevant time

period, are still available online, and were reprinted in the Journal of Pain.

B. Defendants’ Marketing Scheme Misrepresented the Risks and Benefits of Opioids.

160. To convince doctors and patients in Angelina County that opioids can and should

be used to treat chronic pain, Defendants had to convince them that long-term opioid use is non-

addictive, safe, and effective. Knowing they could do so only by deceiving those doctors and

patients about the risks and benefits of long-term opioid use, Defendants made claims that were

not supported by, and were contrary to, the scientific evidence. Defendants have not corrected

their misrepresentations.

PLAINTIFF’S ORIGINAL PETITION 52

 161. Defendants also deceptively trivialized and failed to disclose the risks of long-term

opioid use, particularly the risks of addiction and overdose, through a series of misrepresentations

that have since been conclusively debunked by numerous published studies and the magnitude of

human misery caused by Defendants’ deceptions. These misrepresentations – which are described

below – reinforced each other and created the dangerously misleading impression that opioids are

the best treatment option for any recurrent moderate pain because: (1) only a miniscule number of

patients, if any, would become addicted; (2) all patients with a substantial risk of becoming

addicted to opioids could be readily identified; (3) patients who displayed signs of addiction

probably were not addicted and, in any event, could easily be weaned from the drugs; (4) the use

of higher opioid doses do not escalate risk of addiction or overdose; and (5) “abuse-deterrent”

opioids are reliably safe and effective for perpetual use. Defendants still espouse these

misrepresentations today.

162. First, Defendants falsely claimed the risk of addiction is low and unlikely to

develop when opioids are prescribed, as opposed to those obtained illicitly; and failed to disclose

the greater risk of addiction with prolonged use of opioids.215 For example:

a) Purdue sponsored APF’s Treatment Options: A Guide for People Living

with Pain (2007), which instructed that addiction is rare and limited to
extreme cases of unauthorized dose escalations, obtaining duplicative
opioid prescriptions from multiple sources, or theft. This publication is still
available online;

b) Endo sponsored a website, Painknowledge.com, which claimed in 2009 that

“[p]eople who take opioids as prescribed usually do not become addicted.”
Another Endo website, PainAction.com, stated “Did you know? Most
chronic pain patients do not become addicted to the opioid medications that
are prescribed for them.”;

c) Endo distributed a pamphlet with the Endo logo entitled Living with
Someone with Chronic Pain, which stated that: “Most health care providers

 See, e.g., Manchikanti, Ex. A, at 22 (blaming adverse consequences on abuses and overuses instead of
215

appropriately blaming opioids used as directed). 

PLAINTIFF’S ORIGINAL PETITION 53

 who treat people with pain agree that most people do not develop an
addiction problem.” A similar statement appeared on the Endo website,
www.opana.com;

d) Janssen reviewed, edited, approved, and distributed a patient education

guide entitled Finding Relief: Pain Management for Older Adults (2009),
which described as “myth” the claim that opioids are addictive, and asserted
as fact that “[m]any studies show that opioids are rarely addictive when used
properly for the management of chronic pain.”;

e) Janssen currently runs a website, Prescriberesponsibly.com (last updated

July 2, 2015), which claims that concerns about opioid addiction are
“overestimated”;

f) Purdue sponsored APF’s A Policymaker’s Guide to Understanding Pain &

Its Management – which claims that less than 1% of children prescribed
opioids will become addicted and that pain is undertreated due to
“misconceptions about opioid addiction[].” This publication is still
available online; and

g) Detailers for Purdue, Endo, and Janssen in and around Angelina County
minimized or omitted any discussion with doctors of the risk of addiction;
misrepresented the potential for opioid abuse with purportedly abuse-
deterrent formulations; and routinely did not correct the misrepresentations
noted above.

163. These claims contradict empirical evidence. As noted by the CDC, there is

“extensive evidence” of the “possible harms of opioids (including opioid use disorder [an

alternative term for opioid addiction]).”216 The CDC has explained that “[o]pioid pain medication

use presents serious risks, including…opioid use disorder” and that “continuing opioid therapy for

3 months substantially increases risk for opioid use disorder.”217 In fact, as many as “1 in 4 patients

receiving long-term opioid therapy in primary care settings struggle with opioid use disorder.”218

Among the 12 recommendations by the new CDC guidelines to improve patient care and safety is

that non-opioid therapy is preferred for chronic pain unless there is active cancer or it is for palliative

216
Centers for Disease Control and Prevention, CDC Guideline for Prescribing Opioids for Chronic Pain – United
States 2016, Mar. 18, 2016.
217
Id.
218
Id.

PLAINTIFF’S ORIGINAL PETITION 54

and end-of-life care.219

164. Defendants’ long-standing claims that opioid addiction and overdose are anomalies

largely attributable to patient abuse of the drug, are demonstrably false. Indeed, the majority of

cases “involving injury and death occur in people using opioids exactly as prescribed . . .”220

165. In 2010, a study addressed the rates of opioid overdose with patients receiving

average prescribed daily opioids versus patients receiving medically prescribed chronic opioid

therapy.221 The patients included those receiving three-plus opioid prescriptions within 90-days

for chronic non-cancer pain between 1997 and 2005.222 Patients who received 50-99 mg had a 3.7-

fold increase in overdose risk (95% C.I. 1.5, 9.5) and a 0.7 annual overdose rate.223

166. The authors determined that even though opioids provide some pain relief for

chronic pain, balancing the long-term risks with the benefits was still “poorly understood.”224

Those patients who had not received opioids lately had a lower risk of overdose, however, than

patients consistently receiving opioids at a low dosage.225

167. The authors pointed to previous studies that indicated a rise in opioid-related

overdoses with an increase in prescribing opioids for non-cancer pain, but the belief that such

phenomenon was caused by patients obtaining opioids from non-medical sources.226 This study,

proves for the first time, however, that the risk of overdose is directly linked to the prescription

and use of medically prescribed opioids.227

219
CDC Guidelines for Prescribing Opioids for Chronic Pain, supra.
220
Manchikanti, Ex. A, at 22.
221
Kate M. Dunn, Ph.D., Kathleen W. Saunders, J.D., Overdose and Prescribed Opioids: Association among
Chronic Non-Cancer Pain Patients, Ann. Intern. Med., Dec. 10, 2010, at 2.
222
Id.
223
Id.
224
Id.
225
Dunn, supra, at 6.
226
Id. at 7.
227
Id.

PLAINTIFF’S ORIGINAL PETITION 55

 168. The authors of a Washington study in which the authors obtained Washington

Medicaid data from the Washington Heath Care Authority reached a similar conclusion.228 The

opioid prescription claim history was examined for each “opioid poisoning” for the months that

enrollees received Medicaid FFS prescription benefits.229 The authors concluded that a large

percentage of opioid poisonings happened at lower prescribed doses and in individuals who were

not considered chronic users.230

169. The authors noted that previous opioid guidelines focused on opioid doses above

80-120 mg/d MED even though previous studies showed risk of opioid deaths and poisonings at

much lower doses and that most non-methadone opioid poisonings had been prescribed below

these guidelines levels.231 The authors concluded that only a small percentage of patients are

prescribed opioids at a dosage greater than 120 mg/d MED, but that a large percentage of the

opioids poisonings have been occurring in patients taking lower doses and in patients not

considered chronic users.232 Overdoses were therefore occurring in patients prescribed opioids for

chronic non-cancer pain at increased rates and the overdose risk increased with an average

prescription dose.233 The guidelines and other educational material regarding opioids need to be

changed to reflect the opioid poisoning among this population.234

170. In fact, “[t]he majority of deaths (60%) occur in patients when they are given

prescriptions based on prescribing guidelines by medical boards with 20% of deaths in low dose

opioid therapy . . . .”235 The way to cure the “crisis of opioid use in the United States” is to change

228
Deborah Fulton-Kehoe, Ph.D., Opioid Poisonings in Washington State Medicaid: Trends, Dosing, and
Guidelines, 53 Medical Care 8, Aug. 2015, at 680.
229
Id.
230
Id.
231
Id. at 683.
232
Id. at 684.
233
Fulton-Kehoe, supra.
234
Id.
235
Manchikanti, Ex. A, at 1.

PLAINTIFF’S ORIGINAL PETITION 56

“inappropriate prescribing patterns, which are largely based on a lack of knowledge, perceived

safety, and inaccurate belief of undertreatment of pain.”236

171. Another study found that approximately 60% of overdoses occur in medical users

of opioids prescribed by a single physician to manage chronic pain.237 Non-medical users comprise

only a statistical minority of opioid overdoses.238

172. Scientific evidence underscores the conclusion that low-dose opioid therapy for

chronic pain, opioids taken as prescribed, opioids obtained from a single doctor, and opioids

prescribed pursuant to prescribing guidelines cause many overdoses. Defendants, however,

disseminated contrary messaging throughout their marketing campaigns to sell more opioids.

173. Second, Defendants falsely instructed doctors and patients that signs of addiction

are actually signs of undertreated pain and should be treated by prescribing more opioids.

Defendants called this phenomenon “pseudoaddiction” – a term coined by Dr. David Haddox, who

went to work for Purdue, and popularized by Dr. Russell Portenoy, a KOL for Endo, Janssen, and

Purdue – and claimed that pseudoaddiction is substantiated by scientific evidence. For example:

a) Purdue sponsored Responsible Opioid Prescribing (2007), which taught

that behaviors such as “requesting drugs by name,” “demanding or
manipulative behavior,” seeing more than one doctor to obtain opioids,
and hoarding, are all signs of pseudoaddiction, rather than true addiction.
Responsible Opioid Prescribing remains for sale online. The 2012
edition continues to teach that pseudoaddiction is real;

b) Janssen sponsored, funded, and edited the Let’s Talk Pain website, which
in 2009 stated: “pseudoaddiction . . . refers to patient behaviors that may
occur when pain is under-treated . . . . Pseudoaddiction is different from
true addiction because such behaviors can be resolved with effective pain
management.”;

236
Manchikanti, Ex. A, at 1.
237
Barbara Zedler, M.D., Risk Factors for Serious Prescription Opioid-Related Toxicity or Overdose Among
Veterans Health Administration Patients, Pain Medicine, 2014, at 1912, attached hereto as Exhibit F.
238
Id. 

PLAINTIFF’S ORIGINAL PETITION 57

 c) Endo sponsored a National Initiative on Pain Control (NIPC) CME
program in 2009 titled Chronic Opioid Therapy: Understanding Risk
While Maximizing Analgesia, which promoted pseudoaddiction by
teaching that a patient’s aberrant behavior was the result of untreated pain.
Endo substantially controlled NIPC by funding NIPC projects;
developing, specifying, and reviewing content; and distributing NIPC
materials;

d) Purdue published a pamphlet in 2011 entitled Providing Relief,

Preventing Abuse, which described pseudoaddiction as a concept that
“emerged in the literature” to describe the inaccurate interpretation of
[drug-seeking behaviors] in patients who have pain that has not been
effectively treated.”; and

e) Purdue sponsored a CME program entitled Path of the Patient, Managing

Chronic Pain in Younger Adults at Risk for Abuse. In a role play, a
chronic pain patient with a history of drug abuse tells his doctor that he
is taking twice as many hydrocodone pills as directed. The narrator notes
that because of pseudoaddiction, the doctor should not assume the patient
is addicted even if he persistently asks for a specific drug, seems
desperate, hoards medicine, or “overindulges in unapproved escalating
doses.” The doctor treats this patient by prescribing a high-dose, long-
acting opioid.

174. The 2016 CDC Guideline rejects the concept of pseudoaddiction. The CDC

Guideline nowhere recommends that opioid dosages be increased if a patient is not experiencing

pain relief. To the contrary, the Guideline explains that “[p]atients who do not experience

clinically meaningful pain relief early in treatment…are unlikely to experience pain relief with

longer-term use,”239 and that physicians should “reassess[] pain and function within 1 month”240

in order to decide whether to “minimize risks of long-term opioid use by discontinuing

opioids”241 because the patient is “not receiving a clear benefit.”242

175. Third, Defendants falsely instructed doctors and patients that addiction risk

screening tools, patient contracts, urine drug screens, and similar strategies allowed them to

239
CDC Guidelines for Prescribing Opioids for Chronic Pain, supra.
240
Id.
241
CDC Guidelines for Prescribing Opioids for Chronic Pain, supra.
242
 Id. 

PLAINTIFF’S ORIGINAL PETITION 58

reliably identify and safely prescribe opioids to patients predisposed to addiction. These

misrepresentations were especially insidious because Defendants aimed them at general

practitioners and family doctors who lack the time and expertise to closely manage higher-risk

patients. Defendants’ misrepresentations made these doctors feel more comfortable prescribing

opioids to their patients, and patients more comfortable starting opioid therapy for chronic pain.

For example:

a) Endo paid for a 2007 supplement in the Journal of Family Practice written
by a doctor who became a member of Endo’s speakers’ bureau in 2010. The
supplement, entitled Pain Management Dilemmas in Primary Care: Use of
Opioids, emphasized the effectiveness of screening tools, claiming that
patients at high risk of addiction could safely receive chronic opioid therapy
using a “maximally structured approach” involving toxicology screens and
pill counts;

b) Purdue sponsored a 2011 webinar, Managing Patient’s Opioid Use:

Balancing the Need and Risk, which claimed that screening tools, urine
tests, and patient agreements prevent “overuse of prescriptions” and
“overdose deaths;” and

c) As recently as 2015, Purdue has represented in scientific conferences that

“bad apple” patients – and not opioids – are the source of the addiction crisis
and that once those “bad apples” are identified, doctors can safely prescribe
opioids without causing addiction.

176. Once again, the 2016 CDC Guideline confirms these representations are false. The

Guideline notes that there are no studies assessing the effectiveness of risk mitigation strategies –

such as screening tools, patient contracts, urine drug testing, or pill counts – widely believed by

doctors to detect and deter outcomes related to addiction and overdose.243 As a result, the Guideline

recognizes that doctors should not overestimate the risk screening tools for classifying patients as

high or low risk for opioid addiction because they are insufficient to rule out the risks of long-term

opioid therapy.244

243
CDC Guidelines for Prescribing Opioids for Chronic Pain, supra.  
244
Id. 

PLAINTIFF’S ORIGINAL PETITION 59

 177. Fourth, to underplay the risk and impact of addiction and make doctors feel more

comfortable starting patients on opioids, Defendants falsely claimed that opioid dependence can

easily be addressed by tapering and that opioid withdrawal is not a problem thereby failing to

disclose the increased difficulty of stopping opioids after long-term use.

178. For example, a CME sponsored by Endo, entitled Persistent Pain in the Older

Adult, claimed that withdrawal symptoms can be avoided by tapering a patient’s opioid dose by

10%-20% for 10 days. And Purdue sponsored APF’s A Policymaker’s Guide to Understanding

Pain & Its Management, which claimed that “[s]ymptoms of physical dependence can often be

ameliorated by gradually decreasing the dose of medication during discontinuation.”

179. Defendants deceptively minimized the significant symptoms of opioid withdrawal,

which, as explained in the 2016 CDC Guideline, include drug cravings, anxiety, insomnia,

abdominal pain, vomiting, diarrhea, sweating, tremor, tachycardia (rapid heartbeat), spontaneous

abortion and premature labor in pregnant women, and the unmasking of anxiety, depression, and

addiction – and grossly understated the difficulty of tapering, particularly after long-term opioid

use.

180. Yet the 2016 CDC Guideline recognizes that the duration of opioid use and the

dosage of opioids prescribed should be limited to “minimize the need to taper opioids to prevent

distressing or unpleasant withdrawal symptoms,”245 because “physical dependence on opioids is

an expected physiologic response in patients exposed to opioids for more than a few days.”246

(Emphasis Added.) The Guideline further states that “tapering opioids can be especially

challenging after years on high dosages because of physical and psychological dependence”247 and

245
 CDC Guidelines for Prescribing Opioids for Chronic Pain, supra. 
246
 Id. 
247
Id. 

PLAINTIFF’S ORIGINAL PETITION 60

highlights the difficulties, including the need to carefully identify “a taper slow enough to minimize

symptoms and signs of opioid withdrawal”248 and pausing and restarting tapers depending on the

patient’s response.

181. The CDC also acknowledges the lack of any “high-quality studies comparing the

effectiveness of different tapering protocols for use when opioid dosage is reduced or opioids are

discontinued.”249 Contrary to the Treatment Options distributed by the APF, withdrawal from

opioids involves much more than mere “physical” dependence occurring only when opioids are

stopped suddenly or the dose lowered too quickly.

182. Fifth, Defendants falsely claimed that doctors and patients could increase opioid

dosages indefinitely without added risk and failed to disclose the greater risks to patients at higher

dosages. The ability to escalate dosages was critical to Defendants’ efforts to market opioids for

long-term use to treat chronic pain because, absent this misrepresentation, doctors would have

abandoned treatment when patients built up tolerance and lower dosages did not provide pain

relief. For example:

a) Purdue sponsored APF’s Treatment Options: A Guide for People Living

with Pain (2007), which claims that some patients “need” a larger dose of
an opioid, regardless of the dose currently prescribed. The guide stated that
opioids have “no ceiling dose” and are therefore the most appropriate
treatment for severe pain. This guide is still available for sale online;

b) Endo sponsored a website, painknowledge.com, which claimed in 2009 that

opioid dosages may be increased until “you are on the right dose of
medication for your pain.”;

c) Endo distributed a pamphlet edited by a KOL entitled Understanding Your

Pain: Taking Oral Opioid Analgesics, which was available during the time
period of this Complaint on Endo’s website. In Q&A format, it asked “If I
take the opioid now, will it work later when I really need it?” The response
is, “The dose can be increased. . . . You won’t ‘run out’ of pain relief.”;

248
CDC Guidelines for Prescribing Opioids for Chronic Pain, supra. 
249
 Id. 

PLAINTIFF’S ORIGINAL PETITION 61

 d) Janssen sponsored a patient education guide entitled Finding Relief: Pain
Management for Older Adults (2009), which was distributed by its sales
force. This guide listed dosage limitations as “disadvantages” of other pain
medicines but omitted any discussion of risks of increased opioid dosages;

e) Purdue’s In the Face of Pain website promotes the notion that if a patient’s
doctor does not prescribe what, in the patient’s view, is a sufficient dosage
of opioids, he or she should find another doctor who will;

f) Purdue sponsored APF’s A Policymaker’s Guide to Understanding Pain &

Its Management, which taught that dosage escalations are “sometimes
necessary,” even unlimited ones, but did not disclose the risks from high
opioid dosages. This publication is still available online;

g) Purdue sponsored a CME entitled Overview of Management Options that is

still available for CME credit. The CME was edited by a KOL and taught
that NSAIDs and other drugs, but not opioids, are unsafe at high dosages;
and

h) Purdue presented a 2015 paper at the College on the Problems of Drug

Dependence, the “the oldest and largest organization in the US dedicated to
advancing a scientific approach to substance use and addictive disorders,”
challenging the correlation between opioid dosage and overdose.

183. These claims conflict with the scientific evidence, as confirmed by the FDA and

CDC. As the CDC explains in its 2016 Guideline, the “[b]enefits of high-dose opioids for chronic

pain are not established”250 while the “risks for serious harms related to opioid therapy increase at

higher opioid dosage.”251

184. More specifically, the CDC explains, “there is now an established body of scientific

evidence showing that overdose risk is increased at higher opioid dosages.”252 Similarly, there is

an “increased risk for opioid use disorder, respiratory depression, and death at higher dosages.”253

That is why the CDC advises doctors to avoid increasing dosages above 90 morphine milligram

equivalents per day.

250
 CDC Guidelines for Prescribing Opioids for Chronic Pain, supra. 
251
 Id. 
252
 Id. 
253
 Id. 

PLAINTIFF’S ORIGINAL PETITION 62

 185. Finally, Defendants’ deceptive marketing of the so-called abuse-deterrent

properties of some of their opioids has created false impressions that these opioids reliably curb

addiction and abuse.

186. More specifically, Defendants have made misleading claims about the ability of

their so-called abuse-deterrent opioid formulations to deter use. For example, Endo’s

advertisements for the 2012 reformulation of Opana ER claimed that it was designed to be crush

resistant in a way that suggested it was more difficult to misuse the product. This claim was false.

187. The FDA warned in a 2013 letter that there was no evidence Endo’s design would

provide a reduction in oral, intranasal or intravenous use.254 Moreover, Endo’s own studies, which

it failed to disclose, showed that Opana ER could still be ground and chewed.

188. In a 2016 settlement with the State of New York, Endo agreed not to make

statements in New York that Opana ER was designed to be or is crush-resistant. The State found

those statements false and deceptive because there was no difference in the ability to extract the

narcotic from Opana ER.

189. Similarly, the 2016 CDC Guideline states that no studies support the notion that

“abuse-deterrent technologies [are] a risk mitigation strategy for deterring or preventing abuse,”255

noting that the technologies – even when they work – “do not prevent opioid abuse through oral

intake, the most common route of opioid abuse, and can still be abused by non-oral routes.”256

190. These numerous, long-standing misrepresentations of the risks of long-term opioid

use spread by Defendants successfully convinced doctors and patients to underestimate those risks.

254
See FDA Statement: Original Opana ER Relisting Determination, May 10, 2013.
255
CDC Guidelines for Prescribing Opioids for Chronic Pain, supra.
256
Id.

PLAINTIFF’S ORIGINAL PETITION 63

C. Defendants Grossly Overstated the Benefits of Chronic Opioid Therapy.

191. To convince doctors and patients that opioids should be used to treat chronic pain,

Defendants had to persuade them that there was a significant benefit to long-term opioid use. But

as the 2016 CDC Guideline makes clear, there is “insufficient evidence to determine the long-term

benefits of opioid therapy for chronic pain.”257

192. In fact, the CDC found no evidence showing “a long-term benefit of opioids in pain

and function versus no opioids for chronic pain with outcomes examined at least 1 year later (with

most placebo-controlled randomized trials ≤ 6 weeks in duration)”258 and that other treatments

were more or equally beneficial and less harmful than long-term opioid use.

193. Nonetheless, Defendants were legion in their misrepresentations that opioid drugs

were appropriate for use as a long-term lifestyle. For example:

a) Endo distributed advertisements that claimed that the use of Opana ER for
chronic pain would allow patients to perform demanding tasks like
construction work or work as a chef and portrayed seemingly healthy,
unimpaired subjects;

b) Janssen sponsored and edited a patient education guide entitled Finding

Relief: Pain Management for Older Adults (2009) – which states as “a fact”
that “opioids may make it easier for people to live normally.” The guide
lists expected functional improvements from opioid use, including sleeping
through the night, returning to work, recreation, sex, walking, and climbing
stairs;

c) Purdue ran a series of advertisements for OxyContin in 2012 in medical

journals entitled “pain vignettes,” which were case studies featuring
patients with pain conditions persisting over several months and
recommending OxyContin for them. The ads implied that OxyContin
improves patients’ function;

d) Responsible Opioid Prescribing (2007), sponsored and distributed by Endo

and Purdue, taught that relief of pain by opioids, by itself, improved
patients’ function. The book remains for sale online;

257
CDC Guidelines for Prescribing Opioids for Chronic Pain, supra.
258
Id.

PLAINTIFF’S ORIGINAL PETITION 64

 e) Purdue sponsored APF’s Treatment Options: A Guide for People Living
with Pain (2007), which counseled patients that opioids “give [pain
patients] a quality of life we deserve.” The guide was available online until
APF shut its doors in 2012;

f) Endo’s NIPC website painknowledge.com claimed in 2009 that with

opioids, “your level of function should improve; you may find you are now
able to participate in activities of daily living, such as work and hobbies,
that you were not able to enjoy when your pain was worse.” Elsewhere, the
website promoted improved quality of life (as well as “improved function”)
as benefits of opioid therapy. The grant request that Endo approved for this
project specifically indicated NIPC’s intent to make misleading claims
about function, and Endo closely tracked visits to the site;

g) Endo was the sole sponsor, through NIPC, of a series of CMEs titled
Persistent Pain in the Older Patient, which claimed that chronic opioid
therapy has been “shown to reduce pain and improve depressive symptoms
and cognitive functioning.” The CME was disseminated via webcast;

h) Janssen sponsored, funded, and edited a website, Let’s Talk Pain, in 2009,
which featured an interview edited by Janssen claiming that opioids allowed
a patient to “continue to function.” This video is still available today on
YouTube;

i) Purdue sponsored the development and distribution of APF’s A

Policymaker’s Guide to Understanding Pain & Its Management, which
claimed that “multiple clinical studies” have shown that opioids are
effective in improving daily function, psychological health, and health-
related quality of life for chronic pain patients.” The Policymaker’s Guide
was originally published in 2011 and is still available online today; and

j) Purdue’s, Endo’s, and Janssen’s sales representatives have conveyed and

continue to convey the message that opioids will improve patient function.

194. These claims are unsupported by the scientific literature. The 2016 CDC Guideline

explained, “There is no good evidence that opioids improve pain or function with long-term use”259

and “complete relief of pain is unlikely.”260 The CDC reinforced this conclusion throughout its

2016 Guideline:

a) “No evidence shows a long-term benefit of opioids in pain and function

versus no opioids for chronic pain with outcomes examined at least 1 year

259
CDC Guidelines for Prescribing Opioids for Chronic Pain, supra.
260
Id. (emphasis added).

PLAINTIFF’S ORIGINAL PETITION 65

 later . . . .”;261

b) “Although opioids can reduce pain during short-term use, the clinical
evidence review found insufficient evidence to determine whether pain
relief is sustained and whether function or quality of life improves with
long-term opioid therapy.”;262 and

c) “[E]vidence is limited or insufficient for improved pain or function with

long-term use of opioids for several chronic pain conditions for which
opioids are commonly prescribed, such as low back pain, headache, and
fibromyalgia.”263

195. The CDC also noted that the risks of addiction and death “can cause distress and

inability to fulfill major role obligations.”264

196. Defendants also falsely emphasized or exaggerated the risks of competing products

like NSAIDs so that doctors and patients would look to opioids first for treating chronic pain.

Once again, Defendants’ misrepresentations contradicted non-industry sponsored scientific

evidence. In addition, Purdue misleadingly promoted OxyContin as unique among opioids in

providing 12 continuous hours of pain relief with one dose. In fact, OxyContin does not last for

12 hours – a fact that Purdue has known at all times relevant to this action.

197. According to Purdue’s own research, OxyContin wears off in under six hours in one

quarter of patients and in under 10 hours in more than half. The reason is that OxyContin tablets

release approximately 40% of their active medicine immediately, after which release tapers.

Although the patient experiences a powerful initial response, there is little or no pain relief at the

end of the dosing period because less medicine is released.

198. This phenomenon is known as “end of dose” failure, and the FDA found in 2008

that a substantial number of chronic pain patients taking OxyContin experience it.

261
CDC Guidelines for Prescribing Opioids for Chronic Pain, supra.
262
Id.
263
Id.
264
Id. 

PLAINTIFF’S ORIGINAL PETITION 66

 199. This “end of dose” failure not only renders Purdue’s promise of 12 hours of relief

false and deceptive, it also makes OxyContin more dangerous because the declining pain relief

patients experience toward the end of each dosing period drives them to take more OxyContin

before the next dosing period begins, quickly increasing the amount of drug they are taking and

spurring growing dependence.

200. Purdue’s competitors were aware of this problem. For example, Endo ran

advertisements for Opana ER referring to “real” 12-hour dosing. Nevertheless, Purdue falsely

promoted OxyContin as if it were effective for a full 12 hours. Indeed, Purdue’s sales

representatives continue to tell doctors in and around Angelina County that OxyContin lasts a full

12 hours.

D. Defendants also engaged in Other Unlawful, Unfair, and Fraudulent Misconduct.

201. Other Defendants herein participated in illicit and unlawful prescribing of its drugs.

For example, Purdue did not report illegal prescribing of OxyContin until years after law

enforcement shut down a Los Angeles clinic that prescribed more than 1.1 million OxyContin

tablets. In doing so, Purdue protected its own profits at the expense of public health and safety.

202. The State of New York also found that Endo failed to require sales representatives

to report signs of addiction, diversion, and inappropriate prescribing; paid bonuses to sales

representatives for detailing prescribers who were subsequently arrested or convicted for illegal

prescribing; and failed to prevent sales representatives from visiting prescribers whose suspicious

conduct had caused them to be placed on a no-call list.

E. Defendants Targeted Susceptible Prescribers and Vulnerable Patient Populations.

203. As part of their deceptive marketing scheme, Defendants identified and targeted

susceptible prescribers and vulnerable patient populations in the U.S. and in and around Angelina

PLAINTIFF’S ORIGINAL PETITION 67

County. For example, Defendants focused their deceptive marketing on primary care doctors, who

were more likely to treat chronic pain patients and prescribe opioids, but were less likely to be

educated about treating pain and the risks and benefits of opioids.

204. Defendants also targeted vulnerable patient populations like the elderly and

veterans, who tend to suffer from chronic pain. Defendants targeted these vulnerable patients even

though the risks of long-term opioid use were significantly greater for them.

205. For example, the 2016 CDC Guideline observes that existing evidence shows that

elderly patients taking opioids suffer from elevated fall and fracture risks, greater risk of

hospitalization, and increased vulnerability to adverse drug effects and interactions. The Guideline

therefore concludes that there are “special risks of long-term opioid use for elderly patients” and

recommends that doctors use “additional caution and increased monitoring” to minimize the risks

of opioid use in elderly patients.

206. The same is true for veterans, who are more likely to use anti-anxiety drugs

(benzodiazepines) for post-traumatic stress disorder, which interact dangerously with opioids.

207. Defendants achieved their goal in targeting these vulnerable populations when the

Arthritis Foundation published its Guide to Pain Management in 2003 (“Pain Management

Guide”).265 The Pain Management Guide was published by a neutral third-party that not only

believed the message Defendants had been selling for years, but it continued to relay that message

to patients experiencing chronic pain – elderly patients with arthritis.266

208. The Pain Management Guide was intended for a population of “70 million

Americans who have arthritis or other related diseases.”267 It parroted falsities, such as the low risk

265
Susan Bernstein, The Arthritis Foundation’s Guide to Pain Management, Arthritis Foundation, 2003.
266
Id.
267
Id.

PLAINTIFF’S ORIGINAL PETITION 68

of developing an addiction to opioids and cited Defendants’ false statistic: “The addiction rate

from narcotics is approximately one percent.”268

209. The Arthritis Foundation even accepted and repeated Defendants’ distinction

between dependence and addiction. A person with dependence suggests he or she would

experience withdrawal symptoms upon stopping opioids while addiction “is a self-destructive,

habitual use” of opioids.269 The Pain Management Guide brushes aside concerns about addiction

and recommends higher doses of opioids for patients who develop a dependence on opioids270 –

the exact message that Defendants had been spouting for years.

210. The fact that neutral third parties were relying on and buying Defendants’ false

propositions only verifies Defendants’ successful fraud on the medical and non-medical

community at large.

F. Although Defendants knew that their Marketing of Opioids was False and Deceptive,
they Fraudulently Concealed their Misconduct.

211. Defendants, both individually and collectively, made, promoted, and profited from

their misrepresentations about the risks and benefits of opioids for chronic pain even though they

knew their misrepresentations were false and deceptive. Defendants knew that the marketing

scheme being promoted by Defendants was misleading, inaccurate, and simply false. The history

of opioids, as well as research and clinical experience over the last 20 years, established that

opioids were highly addictive and responsible for a long list of very serious adverse outcomes.

212. In The Journal of the American Medical Association November 2002 edition,

which Defendants meant to reach physicians throughout the nation, Purdue advertised OxyContin

268
Bernstein, supra, at 70-71.
269
Id. at 70.
270
Id.

PLAINTIFF’S ORIGINAL PETITION 69

as a safe drug with minimal safety risks.271 The ad depicts a man and boy fishing with a title in

large white letters exclaiming that “THERE CAN BE LIFE WITH RELIEF” with “LIFE WITH

RELIEF” as the largest words in the advertisement.272 Purdue then informs physicians that “[t]he

most serious risk associated with opioids, including OxyContin, is respiratory depression.”273

213. Purdue fraudulently represented that respiratory depression was not only the most

serious risk for its own drug OxyContin, but for opioids in general, even though it knew that

opioids carried a risk of addiction and death.

214. The ad continues with benign side effects that may occur with the use of

OxyContin, such as “constipation, nausea, sedation, dizziness, vomiting, pruritus, headache, dry

mouth, sweating, and weakness.”274 These side effects are certainly a far cry from addiction or

death. Of course this ad also claims that OxyContin is a “continuous around-the-clock analgesic,”

which is equally false.275

215. Because of the bold misrepresentations and omissions in its ads occurring in the

October 2, 2002 JAMA issue, and one occurring in the November 13, 2002 issue, the FDA wrote

a warning letter to Michael Friedman, the Executive Vice President and Chief Operating Officer

of Purdue.276 Mr. Abrams explained that “[y]our journal advertisements omit and minimize the

serious safety risks associated with OxyContin, and promote it for uses beyond which have been

proven safe and effective.”277 Mr. Abrams reprimanded Purdue for failing to present “any

information” in the advertisement about the “potentially fatal risks” or the potential for abuse

271
The Journal of American Medical Association, Nov. 13, 2002.
272
Id. at 1, 3.
273
Id.
274
Id.
275
JAMA, supra, at 1, 3.
276
Warning Letter from Thomas Abrams, Dir., FDA Div. of Mktg., Adver., & Commc’ns, to Michael Friedman, Exec.
Vice Pres. and COO, Purdue Pharma L.P.
277
Id. at 1.

PLAINTIFF’S ORIGINAL PETITION 70

associated with OxyContin.278

216. Mr. Abrams was concerned that these advertisements suggested such a “broad use

of [OxyContin] to treat pain without disclosing the potential for abuse with the drug and the

serious, potentially fatal risks associated with its use. . . .”279 Purdue’s actions were “especially

egregious and alarming” given “its potential impact on the public health.”280 Mr. Abrams pointed

out to Purdue the reality that “[i]t is particularly disturbing that your November Ad would tout

‘Life with Relief,’ yet fail to warn that patients can die from taking OxyContin.”281

217. Purdue Pharma has consistently disregarded serious harm that it knew Oxycontin

caused. For example, in Kentucky in 2001, three people and one estate sued Purdue for becoming

addicted to OxyContin even though they were taking the drug as prescribed.282 Several similar

lawsuits were filed against Purdue by individuals.283 Dr. J. David Haddox, an executive at Purdue,

responded to these claims: “A lot of these people say, ‘Well, I was taking the medicine like my

doctor told me to,’ and then they start taking more and more and more . . . I don’t see where that’s

my problem.”284

218. Not surprisingly, three current and former executives from Purdue plead guilty in

2007 to criminal charges that they misled regulators, doctors, and patients about OxyContin’s risk

of addiction.285 In pleading guilty to misbranding charges, Purdue admitted it had fraudulently

marketed OxyContin as a drug less prone to addiction and as having fewer side effects than other

278
Warning Letter from Thomas Abrams, supra.
279
Id. at 2.
280
Id.
281
Id. at 4. 
282
Chris Kahn, Maker of OxyContin Faces at least 13 Lawsuits,” July 27, 2001, Port Arthur News.
283
Kahn, supra.
284
Id. 
285
 See Barry Meier, In Guilty Plea, OxyContin Maker to Pay $600 Million, May 10, 2007, available at
http://www.nytimes.com/2007/05/10/business/11drug-web.html; see also Zee, Ex. B, at 3-4. 

PLAINTIFF’S ORIGINAL PETITION 71

opioids.286 In reality, unlike most other opioids, OxyContin contained pure oxycodone without any

other ingredients, which made it a higher-dose narcotic despite its time-release design that Purdue

hawked as ameliorating its addictive potential.287

219. Defendants avoided detection of their fraudulent conduct by disguising their role

in the deceptive marketing through funding and using third parties, such as Front Groups and

KOLs. Doctors and patients trusted these third parties and did not realize that it was the

pharmaceutical companies that were actually feeding them false and misleading information.

220. Defendants also manipulated their promotional materials and the scientific

literature to make it appear that the information promoted was accurate, truthful, and supported by

objective evidence when it was not.

221. Thus, Defendants successfully concealed from the medical community and patients

facts sufficient to arouse suspicion of the claims Angelina County now asserts. Angelina County

did not know of the existence or scope of Defendants’ industry-wide fraud and could not have

acquired such knowledge earlier through the exercise of reasonable diligence.

G. By Increasing Opioid Prescriptions and Use, Defendants’ Deceptive Marketing

Scheme has fueled the Opioid Epidemic and Damaged Angelina County
Communities.

222. Defendants’ misrepresentations deceived doctors and patients about the risks and

benefits of long-term opioid use. Studies reveal that many doctors and patients are unaware of or

do not understand the risks or benefits of opioids. Indeed, patients often report that they were not

warned they might become addicted to opioids prescribed to them. As reported in January 2016,

a 2015 survey of more than 1,000 opioid patients found that 4 out of 10 were not told opioids were

286
 Meier, supra. 
287
Id. 

PLAINTIFF’S ORIGINAL PETITION 72

potentially addictive.288

223. Defendants’ deceptive marketing scheme caused, and continues to cause, doctors

in and around Angelina County to prescribe opioids for chronic pain conditions such as back pain,

headaches, arthritis, and fibromyalgia. Absent Defendants’ fraud, these doctors would not have

prescribed as many opioids that negatively impacted residents of Angelina County.

224. Defendants’ deceptive marketing scheme also caused, and continues to cause,

patients to purchase and use opioids for their chronic pain believing they are safe and effective.

Absent Defendants’ deceptive marketing scheme, fewer patients would be using opioids long-term

to treat chronic pain, and those patients using opioids would be using less of them.

225. Defendants’ deceptive marketing has caused and continues to cause the prescription

and use of opioids to explode. Indeed, this dramatic increase in opioid prescriptions and use

corresponds with the dramatic increase in Defendants’ spending on their deceptive marketing

scheme. Defendants’ spending on opioid marketing totaled approximately $91 million in 2000. By

2011, that spending had tripled to $288 million.

226. The escalating number of opioid prescriptions written by doctors who were

deceived by Defendants’ deceptive marketing scheme is the cause of a correspondingly dramatic

increase in opioid addiction, overdose, and death throughout the U.S. and Angelina County. The

increase in opioid prescriptions equals an increase in “disability, medical costs, subsequent

surgery, and continued or late opioid use.”289

227. Scientific evidence demonstrates a strong correlation between opioid prescriptions

and addiction to opioids. In a 2016 report, the CDC explained that prescribing opioids has

288
 Hazelden Betty Ford Foundation, Missed Questions, Missed Opportunities, Jan. 27, 2016, available at
http://www.hazeldenbettyford.org/about-us/news-and-media/pressrelease/doctors-missing-questions-that-could-
prevent-opioid-addiction. 
289
 Manchikanti, Ex. A, at 23. 

PLAINTIFF’S ORIGINAL PETITION 73

quadrupled since 1999, which has resulted in a parallel increase in opioid overdoses.290 Indeed,

there has been a two-third increase in overdose deaths from using opioids since 2000.291 For these

reasons, the CDC concluded that efforts to rein in the prescribing of opioids for chronic pain are

critical “to reverse the cycle of opioid pain medication misuse that contributes to the opioid

overdose epidemic.”292

228. Due to the increase in opioid overdoses, first responders, such as police officers,

have been and will continue to be in the position to assist people experiencing opioid-related

overdoses.293 In 2016, “over 1,200 law enforcement departments nationwide carried naloxone in

an effort to prevent opioid-related deaths.”294

229. Defendants’ deceptive marketing scheme has also detrimentally impacted children

in Angelina County. Overprescribing opioids for chronic pain has made the drugs more accessible

to school-aged children, who come into contact with opioids after they have been prescribed to

friends or relatives in the same household.

230. Defendants’ conduct has adversely affected Angelina County’s child protection

agencies in the number of children in foster care driven by parental drug addiction. Children with

parents addicted to drugs tend to stay in foster care longer, and they often enter the system having

experienced significant trauma, which makes these cases more expensive for counties like

Angelina County.

290
CDC/NCHS, National Vital Statistics System, Mortality, CDC Wonder, Atlanta, GA: US Department of Health
and Human Services, 2016, available at https://wonder.cdc.gov/; Rudd RA, Seth P, David F, Scholl L, Increases in
Drug and Opioid-Involved Overdose Deaths — United States, 2010–2015, Morb Mortal Wkly Rep., Dec. 16, 2016.
291
CDC, National Vital Statistics System, Mortality, Morb Mortal Wkly Rep., Jan. 1, 2006, at 1378-82, Increases in
Drug and Opioid Deaths – United States, 2000-2014. 
292
 CDC Guideline for Prescribing Opioids for Chronic Pain, supra; see also Rudd, supra.
293
Tex. Att’y Gen. Op. No. KP-0168 (2017). 
294
Id. citing http://www.nchrc.org/law-enforcement/us-law-enforcement-who-carry-naloxone/. 

PLAINTIFF’S ORIGINAL PETITION 74

 231. Opioid addiction is one of the primary reasons that Angelina County residents seek

treatment for substance dependence. A significant number of admissions for drug addiction were

associated with a primary diagnosis of opiate addiction or dependence.

232. Defendants’ creation, through false and deceptive advertising and other unlawful

and unfair conduct, of a virtually limitless opioid market has significantly harmed Angelina County

communities. Defendants’ success in extending the market for opioids to new patients and chronic

pain conditions has created an abundance of drugs available for non-medical and criminal use and

fueled a new wave of addiction and injury. It has been estimated that 60% of the opioids to which

people are addicted come, directly or indirectly, through doctors’ prescriptions.295

233. Law enforcement agencies have increasingly associated prescription drug addiction

with violent and property crimes. Despite strict federal regulation of prescription drugs, local law

enforcement agencies are faced with increasing diversion from legitimate sources for illicit

purposes, including doctor shopping, forged prescriptions, falsified pharmacy records, and

employees who steal from their place of employment. The opioid epidemic has prompted a

growing trend of crimes against pharmacies including robbery and burglary. This ongoing

diversion of prescription narcotics creates a lucrative marketplace.

234. The rise in opioid addiction caused by Defendants’ deceptive marketing scheme

has also resulted in an explosion in heroin use. For example, heroin use has more than doubled in

the past decade among adults aged 18 to 25 years.296 Moreover, heroin-related overdoses in the

United States has more than quadrupled since 2010.297

295
Nathaniel P. Katz, Prescription Opioid Abuse: Challenges and Opportunities for Payers, Am. J. Managed Care,
Apr. 19 2013, at 5 (“The most common source of abused [opioids] is, directly or indirectly, by prescription.”),
available at http://www.ajmc.com/publications/issue/2013/2013-1-vol19-n4/Prescription-Opioid-Abuse-Challenges-
and-Opportunities-for-Payers. 
296
Centers for Disease Control and Prevention, Vital Signs: Today’s Heroin Epidemic – More People at Risk,
Multiple Drugs Abused, MMWR 2015, available at https://www.cdc.gov/vitalsigns/heroin/index.html.
297
Id.

PLAINTIFF’S ORIGINAL PETITION 75

 235. The costs and consequences of opioid addiction are staggering. For example, in

2007, the cost of healthcare due to opioid addiction and dependence was estimated at 25 billion,

the cost of criminal justice was estimated at 5.1 billion, and the cost of lost workplace productivity

was estimated at 25.6 billion.

236. Texas had the second highest healthcare costs in 2015 from opioid abuse in the

nation totaling $1.96 billion.298 One in five Texas high school students has taken prescription drugs

without a valid prescription.299 And four of the top 25 cities for abuse in the United States – two

of them located in East Texas – is in Texas.300

237. Prescription opioid addiction and overdose have an enormous impact on the health

and safety of individuals, as well as communities at large, because the consequences of this

epidemic reach far beyond the addicted individual.

238. Angelina County has also expended funds for false claims submitted on the

County’s health plans that were paid as medically necessary when they were not and prescriptions

for opioids through worker’s compensation benefits.

239. The repercussions for residents of Angelina County therefore include job loss, loss

of custody of children, physical and mental health problems, homelessness and incarceration,

which results in instability in communities often already in economic crisis and contributes to

increased demand on community services such as hospitals, courts, child services, treatment

centers, and law enforcement. Defendants knew, and should have known, about the harms that

their deceptive marketing has caused, and continues to cause, and will cause in the future.

Defendants closely monitored their sales and the habits of prescribing doctors. Their sales

298
Craig, Pandemic, supra.
299
Id.
300
Id. 

PLAINTIFF’S ORIGINAL PETITION 76

representatives, who visited doctors and attended CMEs, knew which doctors were receiving their

messages and how they were responding.

240. Defendants also had access to and carefully watched government and other data

that tracked the explosive rise in opioid use, addiction, injury, and death. Defendants not only

knew, but intended that their misrepresentations would persuade doctors to prescribe and

encourage patients to use their opioids for chronic pain.

241. Defendants’ actions are neither permitted nor excused by the fact that their drug

labels may have allowed, or did not exclude, the use of opioids for chronic pain. FDA approval

of opioids for certain uses did not give Defendants license to misrepresent the risks and benefits of

opioids. Indeed, Defendants’ misrepresentations were directly contrary to pronouncements by, and

guidance from, the FDA based on the medical evidence and their own labels.

242. Nor is Defendants’ causal role broken by the involvement of doctors. Defendants’

marketing efforts were ubiquitous and highly persuasive. Their deceptive messages tainted

virtually every source doctors could rely on for information and prevented them from making

informed decisions. And both doctors and patients in Angelina County relied on information

Defendants distributed whether it was through ads, magazines, trade journals, websites, CMEs,

KOLs, and/or front groups. Defendants also hijacked what doctors wanted to believe – namely,

that opioids represented a means of relieving their patients’ suffering and of practicing medicine

more compassionately.

243. The funds that Angelina County has used and will continue to use for all the costs

associated with Defendants’ false, misleading, and fraudulent marketing are taxpayer funds.

Defendants specifically targeted physicians in Angelina County with fraudulent claims concerning

the benefits of opioids for chronic pain while omitting the lack of efficacy.

PLAINTIFF’S ORIGINAL PETITION 77

 244. Defendants also fraudulently omitted the fact that opioids were addictive even

though they knew, or should have known, that physicians in Angelina County would either use the

misinformation Defendants relayed to them to prescribe opioids to Angelina County residents or

give this information to Angelina County residents, resulting in the over-prescribing and/or

overuse of opioids in Angelina County.

245. Defendants’ actions and omissions were each a cause-in-fact of Angelina County’s

past and future damages. Defendants’ wrongful conduct caused injuries to Angelina County in the

past, continues to cause injuries to Angelina County, and will continue to cause injuries to

Angelina County in the future. Future damages include, but are not limited to, additional resources

for counseling and medication assisted treatment of addicts, medical treatment for overdoses, life

skills training for adolescents, increased law enforcement, and additional resources to treat the

psychological effects of opioids and the underlying conditions that make people susceptible to

opioid addiction, all of which will be obtained through taxpayer resources.

VII. FIRST CAUSE OF ACTION: NEGLIGENT AND/OR

INTENTIONAL CREATION OF A PUBLIC NUISANCE
AGAINST ALL DEFENDANTS

246. Angelina County re-alleges and incorporates by reference each of the allegations

contained in the preceding paragraphs of this Petition as though fully alleged herein.

247. Defendants knowingly encouraged doctors in and around Angelina County to

prescribe, and residents to use, highly addictive opioids for chronic pain even though Defendants

knew using opioids had a high risk of addiction and reduced quality of life.

248. By doing so, Defendants purposefully interfered with Angelina County’s public

health, public safety, public peace, public comfort, and public convenience.

PLAINTIFF’S ORIGINAL PETITION 78

 249. Defendants, individually and in concert with each other, have contributed to and/or

assisted in creating and maintaining a condition that is harmful to the health and safety of Angelina

County residents, and/or unreasonably interferes with the peace and comfortable enjoyment of life

in violation of Texas law.

250. The public nuisance created by Defendants’ actions is substantial and unreasonable

– it has caused and continues to cause significant harm to the community – and the harm inflicted

outweighs any offsetting benefit.

251. The staggering rates of opioid use resulting from Defendants’ marketing efforts

have caused, and continues to cause, harm to the community including, but not limited to:

a) Upwards of 30% of all adults use opioids. These high rates of use have led
t o unnecessary opioid addiction, overdose, injuries, and deaths;

b) Children have been exposed to opioids prescribed to family members or

others resulting in injury, addiction, and death. Easy access to prescription
opioids has made opioids a recreational drug of choice among Angelina
County teenagers; opioid use among teenagers is only outpaced by
marijuana use. Even infants have been born addicted to opioids due to
prenatal exposure causing severe withdrawal symptoms and lasting
developmental impacts;

c) Residents of Angelina County, who have never taken opioids, have endured
both the emotional and financial costs of caring for loved ones addicted to
or injured by opioids and the loss of companionship, wages, or other support
from family members who have used, become addicted to, overdosed on, or
been killed by opioids;

d) More broadly, opioid use and addiction have driven Angelina County
residents’ health care costs higher301;

e) Employers have lost the value of productive and healthy employees who
have suffered from adverse consequences from opioid use;

f) Defendants’ success in extending the market for opioids to new patients and
chronic conditions has created an abundance of drugs available for criminal
301
 See, e.g., Manchikanti, Ex. A, at 14 (stating that the escalating use of opioids in high doses over long periods of
time, lifetime use of long-acting drugs, or the combination has serious consequences for the costs of health care and
economic stability). 

PLAINTIFF’S ORIGINAL PETITION 79

 use and fueled a new wave of addiction and injury. Defendants’ scheme
created both ends of a new secondary market for opioids – providing both
the supply of narcotics to sell and the demand of addicts to buy them;

g) This demand has created additional illicit markets in other opiates,

particularly heroin. The low cost of heroin has led some of those who
initially become addicted to prescription opioids to migrate to cheaper
heroin, fueling a new heroin epidemic in the process;

h) Diverting opioids into secondary, criminal markets and increasing the

number of individuals who are addicted to opioids has increased the
demands on emergency services and law enforcement in Angelina County;

i) All of Defendants’ actions have caused significant harm to the community

– in lives lost; addictions endured; the creation of an illicit drug market and
all its concomitant crime and costs; unrealized economic productivity; and
broken families and homes;

j) These harms have taxed the human, medical, public health, law
enforcement, and financial resources of Angelina County; and

k) Defendants’ interference with the comfortable enjoyment of life of a

substantial number of people is entirely unreasonable because there is
limited social utility to opioid use and any potential value is outweighed by
the gravity of harm inflicted by Defendants’ actions.

252. Defendants knew, or should have known, that promoting opioid use would create a

public nuisance in the following ways:

a) Defendants have engaged in massive production, promotion, and

distribution of opioids for use by the citizens of Angelina County;

b) Defendants’ actions created and expanded the market for opioids,

promoting its wide use for pain management;

c) Defendants misrepresented the benefits of opioids for chronic pain and

fraudulently concealed, misrepresented, and omitted the serious adverse
effects of opioids, including the addictive nature of the drugs; and

d) Defendants knew, or should have known, that their promotion would lead
to addiction and other adverse consequences that the larger community
would suffer as a result.

PLAINTIFF’S ORIGINAL PETITION 80

 253. Defendants’ actions were, at the least, a substantial factor in doctors and patients

not accurately assessing and weighing the risks and benefits of opioids for chronic pain thereby

causing opioids to become widely available and used in Angelina County.

254. Without Defendants’ actions, opioid use would not have become so widespread and

the enormous public health hazard of opioid addiction would not have existed and could have been

averted.

255. The health and safety of the citizens of Angelina County, including those who use,

have used, or will use opioids, as well as those affected by opioid users, is a matter of great public

interest and legitimate concern to Angelina County’s citizens and residents. It was foreseeable to

all Defendants that the burden of the opioid crisis would fall to counties like Angelina County in

the form of social and economic costs. Specifically it was foreseeable that Angelina County would

sustain damages as an employer obligated to provide healthcare coverage to its employees and as

a local government obligated to provide public services to its citizens.

256. The public nuisance created, perpetuated, and maintained by Defendants can be

abated and further reoccurrence of such harm and inconvenience can be prevented.

257. Defendants’ conduct has affected and continues to affect a considerable number of

people within Angelina County and is likely to continue to cause significant harm to patients who

take opioids, their families, and the community at large.

258. Each Defendant created or assisted in creating the opioid epidemic, and each

Defendant is jointly and severally liable for its abatement. Furthermore, each Defendant should be

enjoined from continuing to create, perpetuate, or maintain said public nuisance in Angelina

County. Furthermore, Defendants should compensate Angelina County for the funds it has

expended and continues to expend for medical insurance claims for opioids that were not medically

PLAINTIFF’S ORIGINAL PETITION 81

valid, as well as increased costs of social services, health systems, law enforcement, judicial

system, and treatment facilities.

VIII. SECOND CAUSE OF ACTION: COMMON LAW FRAUD

AGAINST ALL DEFENDANTS

259. Angelina County re-alleges and incorporates by reference each of the allegations

contained in the preceding paragraphs of this Petition as though fully alleged herein.

260. At all relevant and material times, Defendants expressly and/or impliedly warranted

that opioids were safe, of merchantable quality, and fit for use.

261. Defendants’ superior knowledge and expertise, its relationship of trust and

confidence with doctors and the public, its specific knowledge regarding the risks and dangers of

opioids, and its intentional dissemination of promotional and marketing information about opioids

for the purpose of maximizing sales, each gave rise to the affirmative duty to meaningfully disclose

and provide all material information about the risks and harms associated with opioids.

262. At all relevant and material times, Defendants, individually and acting through their

employees and agents, and in concert with each other, fraudulently represented to physicians, who

Defendants knew would justifiably rely on Defendants’ representations, that opioids were safe and

effective for treating chronic pain.

263. Defendants’ false representations were fraudulently made, with the intent or

purpose that healthcare providers and patients would justifiably rely upon them, leading to the

prescription, administration, filling, purchasing, and consumption of opioids in Angelina County.

264. Defendants’ deliberate misrepresentations and/or concealment, suppression, and

omission of material facts as alleged herein include, but are not limited to:

a) Making false and misleading claims regarding the known risks of the
addictive nature of opioids and suppressing, failing to disclose, and
mischaracterizing the addictive nature of opioids and in concomitant costs,

PLAINTIFF’S ORIGINAL PETITION 82

 such as overdoses, deaths, and heroin addiction;

b) Making false and misleading written and oral statements that opioids are
more effective than traditional pain killers for chronic pain, or effective at
all and/or omitting material information showing that opioids are no more
effective than other non-addictive drugs for chronic pain;

c) Issuing false and misleading warnings and/or failing to issue adequate

warnings concerning the risks and dangers of using opioids;

d) Making false and misleading claims downplaying the risk of addiction

when using opioids and/or setting forth guidelines that would purportedly
identify addictive behavior; and

e) Making false and misleading misrepresentations concerning the safety,

efficacy and benefits of opioids without full and adequate disclosure of the
underlying facts which rendered such statements false and misleading.

265. Defendants willfully, wantonly, and recklessly disregarded their duty to provide

truthful representations regarding the safety and risk of opioids, including the fact that upon

information and belief, there was suspicion for diversionary purposes.

266. Defendants made these misrepresentations with the intent that the healthcare

community and patients would rely to their detriment.

267. Defendants’ misrepresentations were made with the intent of defrauding and

deceiving the medical community and consumers to induce and encourage the sale of opioids.

268. Defendants’ fraudulent representations evidence their callous, reckless, willful, and

depraved indifference to the health, safety, and welfare of consumers living in Angelina County.

269. Defendants omitted, misrepresented, suppressed and concealed material facts

concerning the dangers and risk of injuries associated with the use of opioids, as well as the fact

that the product was unreasonably dangerous.

270. Defendants’ purpose was willfully blind to, ignored, downplayed, avoided, and/or

otherwise understated the serious nature of the risks associated with the use of opioids.

PLAINTIFF’S ORIGINAL PETITION 83

 271. Defendants’ failure to stem, rather than fuel spikes of opioid sales was intended to

encourage the sale of opioids, even if the circumstances provided suspicion for diversionary

purposes.

272. The treating medical community and consumers in Angelina County did not know

that Defendants’ representations were false and/or misleading and justifiably relied on them.

273. Defendants had sole access to material facts concerning the dangers and

unreasonable risks of opioids, which they intentionally concealed.

274. As a direct and proximate result of Defendants’ fraudulent misrepresentations and

intentional concealment of facts, upon which the medical community and consumers in Angelina

County reasonably relied, Angelina County suffered actual and punitive damages.

IX. THIRD CAUSE OF ACTION: NEGLIGENCE

AGAINST ALL DEFENDANTS

275. Angelina County re-alleges and incorporates by reference each of the allegations

contained in the preceding paragraphs of this Petition as though fully alleged herein.

276. Defendants have a duty to exercise reasonable care in marketing its opioids to

physicians treating residents of Angelina County and Angelina County residents. Defendants have

breached their duty by knowingly and fraudulently misrepresenting the benefits of, and

downplaying the risks of, opioids for chronic pain.

277. Defendants have used deceitful marketing ploys, KOLs, Front Groups, and other

schemes to increase profits at the cost of public health causing an opioid epidemic. Defendants

have acted willfully, wantonly, and maliciously.

278. As a proximate result, Defendants and its agents have caused Angelina County to

incur excessive costs to treat the opioid epidemic in its county including, but not limited to,

increased costs of social services, health systems, law enforcement, judicial system, and treatment

PLAINTIFF’S ORIGINAL PETITION 84

facilities. It was foreseeable to all Defendants that the burden of the opioid crisis would fall to

counties like Angelina County in the form of social and economic costs. Specifically it was

foreseeable that Angelina County would sustain damages as an employer obligated to provide

healthcare coverage to its employees and as a local government obligated to provide public

services to its citizens.

279. Angelina County and its residents are therefore entitled to actual and punitive

damages.

X. FOURTH CAUSE OF ACTION: GROSS NEGLIGENCE

AGAINST ALL DEFENDANTS

280. Angelina County re-alleges and incorporates by reference each of the allegations

contained in the preceding paragraphs of this Petition as though fully alleged herein.

281. Defendants’ marketing scheme to optimize profits by misrepresenting and falsely

promoting opioids as the panacea to chronic pain was done intentionally.

282. Defendants’ hiring of KOLs, Front Groups, and others to spread its fraudulent

message that opioids were useful and beneficial for chronic pain was grossly negligent and done with

conscious indifference or reckless disregard for the safety of others.

283. Each Defendant’s actions and omissions as described herein, singularly or in

combination with each other, were malicious resulting in damages and injuries to Angelina County

and its residents.

284. At every stage, Defendants knew, or should have known, that their conduct would

create an unreasonable risk of physical harm to others, including Angelina County and its residents,

and should be held liable in punitive and exemplary damages to Angelina County.

PLAINTIFF’S ORIGINAL PETITION 85

 XI. FIFTH CAUSE OF ACTION: UNJUST ENRICHMENT
AGAINST ALL DEFENDANTS

285. Angelina County re-alleges and incorporates by reference each of the allegations

contained in the preceding paragraphs of this Petition as though fully alleged herein.

286. As an expected and intended result of their conscious wrongdoing as set forth in

this Petition, Defendants have profited and benefited from opioid purchases made by Angelina

County and its residents.

287. When Angelina County and its residents purchased opioids, they expected that

Defendants had provided necessary and accurate information regarding those risks. Instead,

Defendants had misrepresented the material facts regarding the risks and benefits of opioids and

distributed or disbursed opioids even though, upon information and belief, there was suspicion for

diversionary purposes.

288. Defendants took undue advantage and received a benefit because the County bore

the cost of the externalities of Defendants’ wrongful conduct. Moreover, the County had no choice

and was effectively required to cover these costs to Defendants’ benefit.

289. Defendants have been unjustly enriched at the expense of Angelina County, and

Angelina County is therefore entitled to damages to be determined by the jury.

PRAYER FOR RELIEF

WHEREFORE, Plaintiff respectfully prays:

a. That the acts alleged herein be adjudged and decreed to be unlawful and that
the Court enter a judgment declaring them to be so;

b. That Defendants be enjoined from, directly or indirectly through KOLs,

Front Groups or other third parties, continuing to misrepresent the risks and
benefits of the use of opioids for chronic pain, and from continuing to
violate Texas law;

PLAINTIFF’S ORIGINAL PETITION 86

 c. That Plaintiff recover all measures of damages, including punitive and
exemplary damages, allowable under the law, and that judgment be entered
against Defendants in favor of Plaintiff;

d. That Plaintiff recover restitution on behalf of Angelina County consumers

who paid for opioids for chronic pain;

e. That Plaintiff recover the costs and expenses of suit, pre- and post-judgment
interest, and reasonable attorneys’ fees as provided by law; and

f. That Defendants be ordered to abate the public nuisance that they created in
in violation of Texas common law.

Date: November 14, 2018

Respectfully Submitted,

SIMON GREENSTONE PANATIER, P.C.

/s/Jeffrey B. Simon
Jeffrey B. Simon
TX State Bar No. 00788420
Amy M. Carter
TX State Bar No. 24004580
1201 Elm Street, Suite 3400
Dallas, Texas 75270
Tel: (214) 276-7680
Fax: (214) 276-7699
[email protected]
[email protected]

PAUL D. HENDERSON, P.C.

Paul D. Henderson
TX State Bar No. 09426300
712 W. Division Ave.
Orange, TX 77630
Tel: (409) 883-9355
Fax: (409) 883-8377
[email protected]

DIES & PARKHURST, L.L.P.

David Dies
TX State Bar No. 05850800

PLAINTIFF’S ORIGINAL PETITION 87

 Steven L. Parkhurst
TX State Bar No. 00797206
1009 Green Avenue
Orange, TX 77630
Tel: (409) 883-0892
Fax: (409) 670-0888
[email protected]
[email protected]
 

PLAINTIFF’S ORIGINAL PETITION 88

  
 
EXHIBIT A
 Pain Physician 2012; 15:ES9-ES38 • ISSN 2150-1149

Health Policy

Opioid Epidemic in the United States

Laxmaiah Manchikanti, MD1, Standiford Helm II, MD2, Bert Fellows, MA3, Jeffrey W. Janata,
PhD4, Vidyasagar Pampati, MSc5, Jay S. Grider, DO, PhD6, and Mark V. Boswell, MD, PhD7

From: 1,3,5Pain Management Center of Over the past two decades, as the prevalence of chronic pain and health care costs have
Paducah, Paducah, KY, and 1,7University exploded, an opioid epidemic with adverse consequences has escalated. Efforts to increase
of Louisville, Louisville, KY; 2Pacific Coast
opioid use and a campaign touting the alleged undertreatment of pain continue to be
Pain Management Center, Laguna Hills,
CA; 4University Hospitals of Cleveland, significant factors in the escalation. Many arguments in favor of opioids are based solely on
Cleveland, OH; and 6University of traditions, expert opinion, practical experience and uncontrolled anecdotal observations.
Kentucky, Lexington, KY. Over the past 20 years, the liberalization of laws governing the prescribing of opioids for
the treatment of chronic non-cancer pain by the state medical boards has led to dramatic
Dr. Manchikanti is Medical Director
of the Pain Management Center of increases in opioid use. This has evolved into the present stage, with the introduction
Paducah, Paducah, KY, and Clinical of new pain management standards by the Joint Commission on the Accreditation of
Professor, Anesthesiology and Healthcare Organizations (JCAHO) in 2000, an increased awareness of the right to pain
Perioperative Medicine, University of relief, the support of various organizations supporting the use of opioids in large doses,
Louisville, Louisville, KY.
Dr. Helm is Medical Director, Pacific and finally, aggressive marketing by the pharmaceutical industry. These positions are based
Coast Pain Management Center, Laguna on unsound science and blatant misinformation, and accompanied by the dangerous
Hills, CA. assumptions that opioids are highly effective and safe, and devoid of adverse events when
Bert Fellows is Director Emeritus of prescribed by physicians.
Psychological Services at the Pain
Management Center of Paducah,
Paducah, KY. Results of the 2010 National Survey on Drug Use and Health (NSDUH) showed that an
Dr. Janata is Division Chief, Psychology, estimated 22.6 million, or 8.9% of Americans, aged 12 or older, were current or past
University Hospitals of Cleveland, Case month illicit drug users, The survey showed that just behind the 7 million people who had
School of Medicine, Cleveland, OH.
used marijuana, 5.1 million had used pain relievers. It has also been shown that only one
Vidyasagar Pampati is a Statistician
at the Pain Management Center of in 6 or 17.3% of users of non-therapeutic opioids indicated that they received the drugs
Paducah, Paducah, KY. through a prescription from one doctor.
Dr. Grider is Associate Professor,
Department of Anesthesiology, The escalating use of therapeutic opioids shows hydrocodone topping all prescriptions
University of Kentucky, Lexington, KY.
Dr. Boswell is Chairman, Department with 136.7 million prescriptions in 2011, with all narcotic analgesics exceeding 238 million
of Anesthesiology and Perioperative prescriptions. It has also been illustrated that opioid analgesics are now responsible for
Medicine, University of Louisville, more deaths than the number of deaths from both suicide and motor vehicle crashes, or
Louisville, KY deaths from cocaine and heroin combined. A significant relationship exists between sales
Address correspondence: of opioid pain relievers and deaths. The majority of deaths (60%) occur in patients when
Laxmaiah Manchikanti, M.D. they are given prescriptions based on prescribing guidelines by medical boards, with 20%
2831 Lone Oak Road of deaths in low dose opioid therapy of 100 mg of morphine equivalent dose or less per
Paducah, Kentucky 42003 day and 40% in those receiving morphine of over 100 mg per day. In comparison, 40%
E-mail: [email protected]
of deaths occur in individuals abusing the drugs obtained through multiple prescriptions,
Disclaimer: There was no external doctor shopping, and drug diversion.
funding in the preparation of this
manuscript. The purpose of this comprehensive review is to describe various aspects of crisis of opioid
Conflict of interest: None.
use in the United States. The obstacles that must be surmounted are primarily inappropriate
Manuscript received: 03/28/2012 prescribing patterns, which are largely based on a lack of knowledge, perceived safety, and
Accepted for publication: 04/09/2012 inaccurate belief of undertreatment of pain.

Free full manuscript: Key words: Opioid abuse, opioid misuse, nonmedical use of psychotherapeutic drugs,
www.painphysicianjournal.com
nonmedical use of opioids, National Survey on Drug Use and Health, opioid guidelines.

Pain Physician 2012; 15:ES9-ES38

www.painphysicianjournal.com
 Pain Physician: Opioid Special Issue July 2012; 15:ES9-ES38

T he Institute of Medicine (IOM) recently published

a report on relieving pain in America (1,2). The
report identified multiple facts, including that
there are more than 116 million Americans with pain
persisting from weeks to years, with financial costs
to condone an increase in prescribing (50,91-93). This
is illustrated by the language in the model guidelines,
which state (65), “no disciplinary action will be taken
against a practitioner based solely on the quantity and/
or frequency of opioids prescribed.” Thus, the use of
ranging from $560 billion to $635 billion per year. The opioids in general, including long-acting and potent
report alluded to the serious problem of the diversion forms of opioids, have dramatically increased due to a
and abuse of opioid drugs, questioning their long-term shift in regulations largely driven by published, albeit
usefulness. The IOM committee reported that when extremely weak, evidence suggesting that opioids are
opioids are used as prescribed; they can be safe and not only highly effective, but also safe in selected per-
effective for acute postoperative pain, procedural pain, sons with chronic non-cancer pain, even though this se-
and patients nearing the end of life who desire more lection criteria are extremely weak and these guidelines
pain relief. While the IOM committee does promote have only facilitated overuse of opioids (31,71,94-98).
pain treatment, including opioids, they do acknowledge Nearly 2 decades later, the scientific evidence for the
a serious crisis in the diversion and abuse of opioids effectiveness of opioids for chronic non-cancer pain
and a lack of evidence for the long-term usefulness of remains unclear (35,71,96,99-119). In addition to ongo-
opioids in treating chronic pain. Along with increases in ing concerns with regard to the lack of effectiveness
the prevalence of chronic pain, health care costs, and of opioids in chronic non-cancer pain (31-38,96,99-119),
adverse consequences due to opioid use, the opioid there is growing evidence of multiple physiologic and
crisis is escalating (1-49). Despite mounting evidence, non-physiologic adverse effects, such as opioid hyper-
efforts to increase opioid use based on the alleged algesia (32,95,96,107,112-124), misuse and abuse (31-
undertreatment of pain continue (50-63). In fact, Stein 39,71,95,96,102,103,110-115,125-140), the inability of
(64) summarized the evidence succinctly, noting that providers to identify and monitor misuse and overuse
“many arguments in favor of opioids are solely based (31,32,36,95,96,126,127,130,138-151), and a steady in-
on traditions, expert opinion, practical experience, and crease in opioid-related fatalities (32,34,37,129,130,152-
uncontrolled anecdotal observations.” 163). In fact, in 2008 drug poisoning in the United
Starting in the late 1990’s, state medical boards States has been reported to contribute to one death
curtailed restrictions on laws governing the prescrib- every 15 minutes (160). Furthermore, opioids have been
ing of opioids for the treatment of chronic non-cancer shown to contribute to one death every 36 minutes in
pain, resulting in a dramatic increase in the number of the United States in 2008. Correlating with these fatali-
prescriptions (65). This development gathered momen- ties, sales and substance abuse treatment admissions
tum with the introduction of new pain management have increased substantially (125-127,159,160,164-168).
standards for in-patient and out-patient medical care With the above background highlighting a steady
implemented by the Joint Commission on the Accredi- increase in fatalities with opioid use and very little evi-
tation of Health Care Organizations (JCAHO) in 2000 dence of effectiveness, it remains to be seen who will
(66) and an increased awareness of the right to pain re- ultimately bear the responsibility for the premature
lief, both of which provided justification for physicians. adoption of opioids as a treatment standard (116). It
(67-70). Other factors fueling an increase in prescrip- has been speculated that in the coming years, there will
tions included aggressive marketing by the pharmaceu- likely be an extensive “postmortem” on the massive
tical industry, the promotion of opioids by numerous opioid treatment movement and the escalating social
physicians and a call for for the increased use of opioids crisis that has accompanied it (116). It is universally ac-
in the treatment of chronic non-cancer pain by myri- cepted that this massive treatment movement has led
ad organizations. These positions, alongside contin- to huge collateral damage in terms of diversion, misuse,
ued assertions that pain is undertreated, were largely and abuse of opioids. The widespread use of opioids
based on untenable science and misinformation, and for chronic non-cancer pain is in direct violation of the
contended that opioids are highly effective and safe established cardinal principles of medical intervention
without adverse effects when prescribed by physicians – that there be compelling evidence of the benefit of a
(31,60,66,71-90). Moreover, a recent examination of therapy prior to its large-scale use (116).
model guidelines for curtailing controlled substance A cautious approach has been advocated in recent
abuse revealed that the guidelines appeared instead years by many (17,33,35,49,110-115,117-119,169). This

ES10 www.painphysicianjournal.com
 Opioid Epidemic in the United States

manuscript is undertaken to evaluate the escalating population. Cocaine was used by 1.5 million, whereas
opioid crisis which although heavily regulated, contin- hallucinogens were used in the past month by 1.2 mil-
ues to be uncontrolled. lion persons (Fig. 1 and Table 1). Next to marijuana, 7.0
million (27%) persons age 12 or older had used pre-
1.0 Non-Medical Use of scription-type psychotherapeutic drugs non-medically
Psychotherapeutic Drugs
in the past month (current use). Of these, 5.1 million
had used pain relievers. The category of psychother-
1.1 Current Non-Medical Use apeutics used in the tables and figures includes the
Results of the 2010 National Survey on Drug Use nonmedical use of any prescription-type pain relievers,
and Health (NSDUH) (170), an annual survey sponsored tranquilizers, stimulants, or sedatives. However, over-
by the Substance Abuse and Mental Health Services Ad- the-counter substances are not included in these stud-
ministration (SAMHSA), showed that an estimated 22.6 ies. The categories of nonmedical use of psychothera-
million, or 8.9% of Americans, age 12 or older, were cur- peutics and pain relievers were well ahead of the illicit
rent (past month) illicit drug users. Illicit drugs include use of cocaine, hallucinogens, inhalants, methamphet-
marijuana, cocaine, heroin, hallucinogens, inhalants, or amine, heroin, and lysergic acid diethylamide (LSD).
prescription-type psychotherapeutics (defined in this Overall, there has been an increase in the cur-
survey as prescription-type pain relievers, tranquilizers, rent use of all illicit drugs and marijuana, without any
stimulants, and sedatives) used non-medically. Marijua- change for psychotherapeutics and hallucinogens and
na was the most commonly used illicit drug with 17.4 a decrease for cocaine from 2002 to 2010, as shown in
million current (past month) users, or 6.9% of the US Fig. 2.

Fig. 1. Past month illicit drug use among persons aged 12 or older: 2010.
Source: Substance Abuse and Mental Health Services Administration. Results from the 2010 National Survey on Drug Use and Health: Sum-
mary of National Findings. http://www.samhsa.gov/data/NSDUH/2k10NSDUH/2k10Results.pdf (170) Access date 2/22/2012.

www.painphysicianjournal.com ES11
 Table 1. Types of illicit drug use in the past month among persons aged 12 or older: Numbers in thousands, from 1998 to 2010.

ES12
12-Year %
Drugs 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 change from
1998 to 2010
Nonmedical Use of 2,477 3,952 3,849 4,811 6,287 6,451 6,110 6,491 7,095b 6,895a 6,224 6,953 6,967
181%
Psychotherapeutics2,3 (1.1%) (1.8%) (1.7%) (2.1%) (2.7%) (2.7%) (2.5% ) (2.7%) (2.9%b) (2.8%a) (2.5%) (2.8%) (2.7%)
3,497
2,621 2,782 4,377 4,693 4,404 4,658 5,220 5,174 4,747 5,257 5,100
Pain Relievers -- NA
(1.2%) (1.2%) (1.9%) (2.0%) (1.8%) (1.9%) (2.1%) (2.1%) (1.9%) (2.1%) (2.0%)
(1.6%)
325 334 276 369 435 510 564
OxyContin® -- -- -- -- -- -- NA
(0.1%) (0.1%) (0.1%a) (0.1%) (0.2%) (0.2%) (0.2%)
655 1,097 1,000 1,358 1,804 1,830 1,616 1,817 1,766 1,835 1,800 2,010 2,160
Tranquilizers 230%
(0.3%) (0.5%) (0.4%) (0.6%) (0.8%) (0.8%) (0.7%) (0.7%) (0.7%) (0.7%) (0.7%) (0.8%) (0.9%)
1,312b 1,188b
633 950 788 1,018 1,303b 1,310b 1,385b 1,053 904 1,290 1,077
Stimulants 70%
(0.3%) (0.4%) (0.4%) (0.5%) (0.6%b) (0.6%b) (0.6%b) (0.4%) (0.4%) (0.5%) (0.4%)
(0.5%b) (0.5%b)
175
210 229 306 436b 294 265 272 385 346 234 370 374
Sedatives3 78%
(0.1%) (0.1%) (0.1%) (0.2%b) (0.1%) (0.1%) (0.1%) (0.2%a) (0.1%) (0.1%) (0.1%) (0.1%)
(0.1%)
Marijuana and 11,016 10,458 10,714 12,122 14,584 14,638 14,576 14,626 14,813 14,448 15,203 16,718 17,373
58%
Hashish (5.0%) (4.7%) (4.8) (5.4%) (6.2%) (6.2%) (6.1%) (6.0%) (6.0%) (5.8%) (6.1%) (6.6%) (6.9%)
1,667
1,750 1,552 1,213 2,020 2,281 2,021 2,397 2,421 2,075 1,855 1,637 1,466
Cocaine -16%
(0.8%) (0.7%) (0.5%) (0.9%) (1.0%) (0.8%) (1.0%) (1.0%) (0.7%) (0.6%)
(0.7%)
TOTAL ILLICIT 13,615 13,829 14,027 15,910 19,522 19,470 19,071 19,720 20,357 19,857 20,077 21,813 22,622
66%
DRUGS1 (6.2%) (6.3%) (6.3%) (7.1%) (8.3%) (8.2%) (7.9%) (8.1%) (8.3%) (8.0%) (8.0%) (8.7%) (8.9%)
-- Not available.
Note: 2002 to 2008 data is based on 2008 National Survey on Drug Use and Health Survey Report.
a Difference between estimate and 2008 estimate is statistically significant at the 0.05 level. b Difference between estimate and 2008 estimate is statistically signifi-
cant at the 0.01 level.
Pain Physician: Opioid Special Issue July 2012; 15:ES9-ES38

1 Illicit Drugs include marijuana/hashish, cocaine (including crack), heroin, hallucinogens, inhalants, or prescription-type psychotherapeutics used nonmedi-
cally. Illicit Drugs Other
Than Marijuana include cocaine (including crack), heroin, hallucinogens, inhalants, or prescription-type psychotherapeutics used nonmedically. The estimates
for Nonmedical Use of Psychotherapeutics, Stimulants, and Methamphetamine incorporated in these summary estimates do not include data from the metham-
phetamine items added in 2005 and 2006.
2 Nonmedical use of prescription-type psychotherapeutics includes the nonmedical use of pain relievers, tranquilizers, stimulants, or sedatives and does not
include over-the counter drugs.
3 Estimates of Nonmedical Use of Psychotherapeutics, Stimulants, and Methamphetamine in the designated rows include data from methamphetamine items added
in 2005 and 2006 and are not comparable with estimates presented in NSDUH reports prior to the 2007 National Findings report. For the 2002 through 2005 survey
years, a Bernoulli stochastic imputation procedure was used to generate adjusted estimates comparable with estimates for survey years 2006 and later.
Source: SAMHSA, Office of Applied Studies, National Survey on Drug Use and Health, 1998 - 2010.
www.samhsa.gov/data/NSDUH/2k10NSDUH/2k10Results.pdf (170) Access date 2/22/2012

www.painphysicianjournal.com
 Opioid Epidemic in the United States

Fig. 2. Past month use of selected illicit drugs among persons aged 12 or older: 2002-2010.
Source: Substance Abuse and Mental Health Services Administration. Results from the 2010 National Survey on Drug Use and Health:
Summary of National Findings. http://www.samhsa.gov/data/NSDUH/2k10NSDUH/2k10Results.pdf (170) Access date 2/22/2012

1.2 Past Year Initiates 1.3 Past Year Use

In 2010, there were 2.4 million persons age 12 or The analysis of long-term statistics based on yearly
older who used psychotherapeutics non-medically for use of illicit drugs is disturbing. The past year use of il-
the first time within the past year. Numbers of new licit drugs in 2010 was 38.806 million, or 15.3% of the
users for specific psychotherapeutics in 2010 were 2.0 population (Table 3). Nonmedical use of psychothera-
million for pain relievers, 1.2 million for tranquilizers, peutics for the past year in the 2010 survey was 16.031
624,000 for stimulants, and 252,000 for sedatives (Table million or 6.3% population age 12 or older, compared
2 and Fig. 3). The specific drug categories with the larg- to 2.6% of the population in 1998. Of importance is the
est number of recent initiatives among persons age 12 fact that nonmedical use of psychotherapeutics was just
or older were nonmedical use of pain relievers (2,004 behind marijuana and hashish with use by 11.5% of
million) and marijuana (2,426 million), followed by the population age 12 or older in 2010, increased from
nonmedical use of tranquilizers (1,238 million), ecstasy 8.6% in 1998. Overall, nonmedical use of psychothera-
(0.937 million), inhalants (0.793 million), cocaine (0.637 peutics increased 178% from 1998 to 2010, compared
million), and stimulants (0.624 million) (Fig. 3). More to marijuana 56% and cocaine at 17%.
strikingly, in 2010, the number of new nonmedical users
of OxyContin (oxycodone) age 12 or older was 598,000 1.4 Lifetime Use
with an average age at first use of 22.8 years among Lifetime use of illicit drugs (lifetime use indicates
those age 12 to 49 (170). use of a specific drug at least once in the respondent’s

www.painphysicianjournal.com ES13
 Table 2. Past year initiates for illicit drugs from 1998 to 2010 (numbers in thousands) for 12 years.

ES14
1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 12-Year
% change
Drugs
from 1998
to 2010

Pain 1,548 1,810 2,268 2,400 2,320 2,456 2,422 2,193 2,150 2,147 2,176 2,179 2,004 29%
Relievers2

Tranquilizers 860 916 1,298 1,212 1,184 1,071 1,180 1,286 1,112 1,232 1,127 1,226 1,238 44%

Stimulants2 648 706 808 853 783 715 793a 647 845b 642 599 702 624 -4%

Sedatives 147 164 191 225 209 194 240 247 267 198 181 186 252 71%

Marijuana 2,498 2,640 2,746 2,793 2,196 1,973 2,142 2,114 2,063 2,090 2,208 2,361 2,426 -3%

Cocaine 868 917 1,002 1,140 1,032b 986b 998b 872a 977b 906b 722 617 637 -27%

with 119,508 or 47.1% of the population. Similarly,

age 12 or older has been increasing over the years (Ta-

persons age 12 or older was slightly more than 2009

ble 4). In 2010, the lifetime use of illicit drugs among

nonmedical use of psychotherapeutics remained the

lifetime), including psychotherapeutics, among persons
Heroin 140 121 114 154 117 92 118 108 91 106 114 180 140 0%

Note: 2002 to 2008 data is based on 2008 National Survey on Drug Use and Health Survey Report.
-- Not available.
a Difference between estimate and 2008 estimate is statistically significant at the 0.05 level.
b Difference between estimate and 2008 estimate is statistically significant at the 0.01 level.
1 Illicit Drugs include marijuana/hashish, cocaine (including crack), heroin, hallucinogens, inhalants, or prescription-type psychotherapeutics used
nonmedically. Illicit Drugs Other Than Marijuana include cocaine (including crack), heroin, hallucinogens, inhalants, or prescription-type psychothera-
peutics used nonmedically. The estimates for Nonmedical Use of Psychotherapeutics, Stimulants, and Methamphetamine incorporated in these summary
estimates do not include data from the methamphetamine items added in 2005 and 2006. See Section B.4.8 in Appendix B of the Results from the 2008
National Survey on Drug Use and Health: National Findings.
2 Nonmedical use of prescription-type psychotherapeutics includes the nonmedical use of pain relievers, tranquilizers, stimulants, or sedatives and does
Pain Physician: Opioid Special Issue July 2012; 15:ES9-ES38

not include over-the counter

drugs.
3 Estimates of Nonmedical Use of Psychotherapeutics, Stimulants, and Methamphetamine in the designated rows include data from methamphetamine
items added in 2005 and 2006 and are not comparable with estimates presented in NSDUH reports prior to the 2007 National Findings report. For the
2002 through 2005 survey years, a Bernoulli stochastic imputation procedure was used to generate adjusted estimates comparable with estimates for sur-
vey years 2006 and later.
Source: Substance Abuse and Mental Health Services Administration. Results from the 2010 National Survey on Drug Use and Health: Summary of Na-
tional Findings. http://www.samhsa.gov/data/NSDUH/2k10NSDUH/2k10Results.pdf (170) Access date 2/22/2012

Contin increased significantly from 1.9 million in 2005

www.painphysicianjournal.com
to 2.4% in 2010 (171). Lifetime use of illicit drugs in per-
to 6.1 million in 2010, or 0.8% of the population in 2005
million using prescription psychotherapeutic drugs for
same from 2009 with 20.4% in 2010, or almost 51.6

nonmedical purposes. Among the subgroups, only Oxy-

 Opioid Epidemic in the United States

Fig. 3. Past year initiates for specific illicit drugs among persons aged 12 or older: 2010.
Source: Substance Abuse and Mental Health Services Administration. Results from the 2010 National Survey on Drug Use and Health:
Summary of National Findings. http://www.samhsa.gov/data/NSDUH/2k10NSDUH/2k10Results.pdf (170) Access date 2/22/2012

sons age 12 or older was topped by marijuana (41.9% est rate among 21 to 25 year olds 20.5% (Fig. 6) (144).
of the population) followed by nonmedical use of psy- In 2010, adults age 26 or older were less likely to be
chotherapeutics (20.4% of the population). current drug users than youths age 12 to 17 or young
adults age 18 to 25 (6.6 versus 10.1 and 21.5%, respec-
1.5 Abuse Based on Age tively). However, there were more drug users age 26 or
In 2010, young adults age 18 to 25 demonstrated older (12.8 million) than users in the 12-to-17-year age
rates of current use of illicit drugs to be higher (21.5%) group (2.5 million) and 18-to-25-year age group (7.3
than for youths age 12 to 17 (10.1%) and adults age 26 million) combined.
or older (6.6%), with 6.9% using marijuana, 2.7% using
psychotherapeutics non-medically, 0.6% using cocaine, 1.6 Abuse Based on Gender
and 0.5% using hallucinogens among young adults 18- In 2010, the survey results were similar to prior
25 (Fig. 4). Past month nonmedical use of prescription- years with males being more likely than females to be
type drugs among young adults increased from 20.2% current illicit drug users (11.2% versus 6.8%). Males
in 2002 to 21.5% in 2010. This was primarily due to an were more likely than females to be past month users
increase in the rate of pain reliever use which was 4.1% of marijuana (9.1% versus 4.7%). Rates of past month
in 2002 and 4.9% in 2006 (170). As illustrated in Figure nonmedical use of psychotherapeutic drugs among
5, overall illicit drug use increased from 8.3% to 8.9% in males and females was 3% and 2.5%, pain relievers was
2010 in the age group from 18 to 25. 2.3% and 1.7%, cocaine was 0.8% and 0.4% and hal-
Rates of past month illicit drug use varied with age. lucinogens was 0.6% and 0.3% (170).
Through the adolescent years from 12 to 17, the rates
of current illicit drug use in 2010 increased from 4.0% 1.7 Abuse During Pregnancy
at ages 12 or 13, to 9.3% at ages 14 or 15, to 16.6% Among pregnant woman age 15 to 44 years, a sig-
at ages 16 or 17 (170). The highest rate of 23.1% was nificantly lower proportion of women used illicit drugs
noted among persons age 18 to 20, with the next high- in the past month (4.4%) compared to 10.9% of their

www.painphysicianjournal.com ES15
 Table 3. Types of illicit drug use in the past year among persons aged 12 or older: numbers in thousands from 1998 to 2010 (12 years).
12-year

ES16
% change
Drugs 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010
from 1998
to 2010
Nonmedical Use of 5,759 9,220 8,761 11,102 14,795 15,163 14,849 15,346 16,482 b 16,280a 15,166 16,006 16,031
178%
Psychotherapeutics2, 3 (2.6%) (4.2%) (3.9%) (4.9%) (6.3%) (6.4%) (6.2%) (6.3%) (6.7% b) (6.6%a) (6.1%) (6.4%) (6.3%)
6,582 6,466 8,353 10,992a 11,671 11,256 11,815 12,649 12,466 11,885 12,405 12,213 85%
Pain Relievers --
(3.0%) (2.9%) (3.7%) (4.7%) (4.9%) (4.7%) (4.9%) (5.1% a) (5.0%) (4.8%) (4.9%) (4.8%) From 1999
1,213a 1,226 1,323 1,422 1,459 1,677 1,869 54%
OxyContin® -- -- -- -- -- --
(0.5%) (0.5%) (0.5%) (0.6%) (0.6%) (0.7%) (0.7%) From 2004
1,940 2,728 2,731 3,673 4,849 5,051 5,068 5,249 5,058 5,282 5,103 5,460 5,581
Tranquilizers 188%
(0.9%) (1.2%) (1.2%) (1.6%) (2.1%) (2.1%) (2.1%) (2.2%) (2.1%) (2.1%) (2.0%) (2.2%) (2.2%)
1,489 2,291 2,112 2,486 3,380b 3,031a 3,254b 3,088a 3,791b 2,998 2,639 3,060 2,887
Stimulants3 94%
(0.7%) (1.0%) (0.9%) (1.1%) (1.4%b) (1.3%b) (1.4%b) (1.3%b) (1.5%b) (1.2%) (1.1%) (1.2%) (1.1%)
522 631 611 806 981b 831 a 737 750 926 b 864 a 621 811 907
Sedatives 56%
(0.2%) (0.3%) (0.3%) (0.4%) (0.4%b) (0.3%a) (0.3%) (0.3%) (0.4%b) (0.3%a) (0.2%) (0.3%) (0.4%)
Marijuana and 18,710 19,102 18,589 21,086 25,755 25,231 25,451 25,375 25,378 25,085 25,768 28,521 29,206
56%
Hashish (8.6%) (8.6%) (8.3%) (9.3%c) (11.0%a) (10.6%) (10.6%) (10.4%) (10.3%) (10.1%) (10.3%) (11.3%) (11.5%)
5,658
3,811 3,742 3,328 4,186 5,902a 5,908a 5,523 6,069b 5,738 5,255 4,797 4,449
Cocaine (2.4% 17%
(1.7%) (1.7%) (1.5%) (1.9%c) (2.5%b) (2.5%b) (2.3%) (2.5%b) (2.3%) (2.1%) (1.9%) (1.8%)
a)
TOTAL ILLICIT 23,115 25,402 24,535 28,409 35,132 34,993 34,807 35,041 35,775 35,692 35,525 37,957 38,806
68%
DRUGS1 (10.6%) (11.5%) (11.0%) (12.6%c) (14.9%a) (14.7%) (14.5%) (14.4%) (14.5%) (14.4%) (14.2%) (15.1%) (15.3%)

-- Not available.
Note: 2002 to 2010 data is based on 2010 National Survey on Drug Use and Health Survey Report. a Difference between estimate and 2010 estimate is sta-
tistically significant at the 0.05 level. b Difference between estimate and 2010 estimate is statistically significant at the 0.01 level.
1 Illicit Drugs include marijuana/hashish, cocaine (including crack), heroin, hallucinogens, inhalants, or prescription-type psychotherapeutics used non-
medically. Illicit drugs other than marijuana include cocaine (including crack), heroin, hallucinogens, inhalants, or prescription-type psychotherapeutics
used non-medically. The estimates for nonmedical use of psychotherapeutics, stimulants, and methamphetamine incorporated in these summary estimates
do not include data from the methamphetamine items added in 2005 and 2006.
Pain Physician: Opioid Special Issue July 2012; 15:ES9-ES38

2 Nonmedical use of prescription-type psychotherapeutics includes the nonmedical use of pain relievers, tranquilizers, stimulants, or sedatives and does
not include over-the counter drugs.
3 Estimates of nonmedical use of psychotherapeutics, stimulants, and methamphetamine in the designated rows include data from methamphetamine
items added in 2005 and 2006 and are not comparable with estimates presented in NSDUH reports prior to the 2007 National Findings report. For the 2002
through 2005 survey years, a Bernoulli stochastic imputation procedure was used to generate adjusted estimates comparable with estimates for survey years
2006 and later.
Source: Substance Abuse and Mental Health Services Administration. Results from the 2010 National Survey on Drug Use and Health: Summary of Na-
tional Findings. http://www.samhsa.gov/data/NSDUH/2k10NSDUH/2k10Results.pdf (170). Access date 2/22/2012

www.painphysicianjournal.com
 Table 4. Types of illicit drugs of lifetime use among persons aged 12 or older: numbers in thousands, 1998 – 2010.

12-Year
% change
Drug 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010
from 1998
to 2010

Nonmedical Use of 20,193 34,076 32,443 36,028 47,958 b 49,001b 49,157 49,571 a 50,965 50,415 51,970 51,771 51,641
156%

www.painphysicianjournal.com
Psychotherapeutics2 (9.2%) (15.4%) (14.5%) (16.0%) (20.4%) (20.6%) (20.4%) (20.4%) (20.7%) (20.3%) (20.8%) (20.6%) (20.4%)

19,888 19,210 22,133 29,611 b 31,207 b 31,768 b 32,692 b 33,472 33,060 a 34,861 35,046 34,776 75%
Pain Relievers --
(9.0%) (8.6%) (9.8%) (12.6% b) (13.1% a) (13.2% a) (13.4%) (13.6%) (13.3%) (14.0%) (13.9%) (13.7%) From 1999
1,924 b 2,832 b 3,072 b 3,481 b 4,098 b 4,354 4,842 5,829 6,121 218%
OxyContin® -- -- -- --
(0.8% b) (1.2% b) (1.3% b) (1.4% b) (1.7% b) (1.8%) (1.9%) (2.3%) (2.4%) From 2002
7,726 13,860 13,007 13,945 19,267 b 20,220 19,852 a 21,041 21,303 20,208 21,476 21,755 22,103
Tranquilizers 186%
(3.5%) (6.3%) (5.8%) (6.2%) (8.2%) (8.5%) (8.3%) (8.7%) (8.7%) (8.2%) (8.6%) 8.6%) (8.7%)
9,614 15,922 14,661 16,007 23,496 b 23,004 a 22,297 20,983 22,468 21,654 21,206 21,930 21,660
Stimulants 125%
(4.4%) (7.2%) (6.6%) (7.1%) (10.0% b) (9.7% b) (9.3% b) (8.6%) (9.1% a) (8.7%) (8.5%) (8.7%) (8.5%)
4,640 7,747 7,142 7,477 9,960 a 9,510 9,891 8,982 8,822 8,396 8,882 8,605 7,631
Sedatives 64%
(2.1%) (3.5%) (3.2%) (3.3%) (4.2% b) (4.0% a) (4.1% a) (3.7%) (3.6%) (3.4%) (3.6%) (3.4%a) (3.2%)
Marijuana and 72,070 76,428 76,321 83,272 94,946 b 96,611 b 96,772 b 97,545 b 97,825 b 100,518 102,404 104,446 106,232
47%
Hashish (33.0%) (34.6%) (34.2%) (36.9%c) (40.4%) (40.6%) (40.2%) (40.1%) (39.8% a) (40.6%) (41.0%) (41.5%) (41.9%)
b a b
23,089 25,406 24,896 27,788 33,910 34,891 34,153 b 33,673 35,298 35,882 36,773 36,599 37,210
Cocaine 61%
(10.6%) (11.5%) (11.2%) (12.3%) (14.4%) (14.7%) (14.2%) (13.8%) (14.3%) (14.5%) (14.7%) (14.5%) (14.7%)
108,255
TOTAL ILLICIT 78,123 87,734 86,931 94,140 110,205 b 110,057 b 112,085 b 111,774 b 114,275a 117,325 118,705 119,508
b 53%
DRUGS1 (35.8%) (39.7%) (38.9%) (41.7%c) (46.4%) (45.8% a) (46.1%) (45.4% b) (46.1%) (47.0%) (47.1%) (47.1%)
(46.0%)
Opioid Epidemic in the United States

-- Not available.
Note: 2002 to 2010 data is based on 2010 National Survey on Drug Use and Health Survey Report.
a Difference between estimate and 2010 estimate is statistically significant at the 0.05 level.
b Difference between estimate and 2010 estimate is statistically significant at the 0.01 level.
1 Illicit Drugs include marijuana/hashish, cocaine (including crack), heroin, hallucinogens, inhalants, or prescription-type psychotherapeutics used
non-medically. Illicit drugs other than marijuana include cocaine (including crack), heroin, hallucinogens, inhalants, or prescription-type psycho-
therapeutics used non-medically. The estimates for nonmedical use of psychotherapeutics, stimulants, and methamphetamine incorporated in these
summary estimates do not include data from the methamphetamine items added in 2005 and 2006.
2 Nonmedical use of prescription-type psychotherapeutics includes the nonmedical use of pain relievers, tranquilizers, stimulants, or sedatives and
does not include over-the counter drugs.
3 Estimates of nonmedical use of psychotherapeutics, stimulants, and methamphetamine in the designated rows include data from methamphet-
amine items added in 2005 and 2006 and are not comparable with estimates presented in NSDUH reports prior to the 2007 National Findings re-
port. For the 2002 through 2005 survey years, a Bernoulli stochastic imputation procedure was used to generate adjusted estimates comparable with
estimates for survey years 2006 and later.
Source: Substance Abuse and Mental Health Services Administration. Results from the 2010 National Survey on Drug Use and Health: Summary of
National Findings. http://www.samhsa.gov/data/NSDUH/2k10NSDUH/2k10Results.pdf (170) Access date 2/22/2012

ES17
 Pain Physician: Opioid Special Issue July 2012; 15:ES9-ES38

Fig. 4. Comparative analysis of past month use of illicit drugs among various age groups.
Source: Substance Abuse and Mental Health Services Administration. Results from the 2010 National Survey on Drug Use and Health: Sum-
mary of National Findings. http://www.samhsa.gov/data/NSDUH/2k10NSDUH/2k10Results.pdf (170) Access date 2/22/2012

Fig. 5. Past month use of selected illicit drugs among young adults aged 18 to 25: 2002-2010.
Source: Substance Abuse and Mental Health Services Administration. Results from the 2010 National Survey on Drug Use and Health: Sum-
mary of National Findings. http://www.samhsa.gov/data/NSDUH/2k10NSDUH/2k10Results.pdf (170) Access date 2/22/2012

ES18 www.painphysicianjournal.com
 Opioid Epidemic in the United States

Fig. 6. Past month illicit drug use among persons aged 12 or older, by age: 2009 and 2010.
Source: Substance Abuse and Mental Health Services Administration. Results from the 2010 National Survey on Drug Use and Health: Sum-
mary of National Findings. http://www.samhsa.gov/data/NSDUH/2k10NSDUH/2k10Results.pdf (170) Access date 2/22/2012

1.10 Drug Abuse Among Criminals

nonpregnant counterparts. These figures are based on In 2010, an estimated 1.5 million adults age 18 or
data averaged for 2009 and 2010 (170). older who were on parole or supervised release from jail
during the past year had higher rates of dependence on
1.8 Abuse Based on Employment or abuse of a substance (27%) than their counterparts
Employment also seemed to have a significant in- who were not on parole or supervised release during
fluence in 2010. Among adults age 18 or older, the rate the past year (8.7%). In 2010, probation status was as-
of illicit drug use was higher for unemployed persons sociated with substance dependence or abuse. The rate
(17.5%) than for those who were employed full time of substance dependence or abuse was 29.9% among
(8.4%) or part time (11.2%) (170). adults who were on probation during the past year,
which was significantly higher than the rate among
1.9 Regional Variations adults who were not on probation during the past year
There were also differences based on geographic was 8.3% (170).
area among persons age 12 or older in 2010. The rate of
current illicit drug use in 2010 was 11.0% in the West, 1.11 Driving Under the Influence
9.4% in the Northeast, 8.2% in the Midwest, and 7.8% Driving under the influence of illicit drugs is a crim-
in the South (170). Further, the rate of current illicit drug inal act and dangerous to the public. In 2010, 10.6 mil-
use in metropolitan areas was higher than the rate in lion persons, or 4.2% of the population age 12 or older,
non-metropolitan areas with 9.4% in large metropoli- reported driving under the influence of illicit drugs dur-
tan counties, 8.8% in small metropolitan counties, and ing the past year. This rate was highest among young
7.5% in non-metropolitan counties as a group (170). adults age 18 to 25 with 12.7% (170).

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 Pain Physician: Opioid Special Issue July 2012; 15:ES9-ES38

major depressive disorder (171). Further, SPD indicates

1.12 Frequency of Abuse a respondent recently experienced heightened distress
Among past year marijuana users age 12 or older in symptomatology that may be affecting health and be-
2010, the following patterns were revealed (170): havior during the past 30 days. However, this distress
• 15.7% used marijuana on 300 or more days within may be part of a chronic psychological disturbance
the past 12 months, translating to 4.6 million using (even SMI) or may represent a temporary disturbance
marijuana on a daily or almost daily basis over a that could subside after a brief period of adjustment.
12-month period.
• 39.9%, or 6.9 million, used the drug on 20 or more 2.1 Serious Medical Illness and Drug Abuse
days in the past month (current use). The prevalence of SMI in 2010 was shown in 11.4
million adults, representing 5.0% of all adults, with the
2.0 Mental Health Problems and
highest rates being in adults age 18 to 25 (7.7%) and
Nonmedical Use Of Drugs
lowest for adults age 50 or older (3.2%) as shown in Fig-
The NSDUH survey of 2010 evaluated the preva- ure 7 (171). The prevalence of SPD among women age
lence and treatment of serious mental illness (SMI), 18 or older was higher (6.5%) than among men (3.4%)
serious psychological distress (SPD), and major depres- in that age group (171).
sive episode (MDE) and the association of these prob-
lems with substance use and substance dependency or 2.2 Major Depressive Episodes and Drug
abuse. SPD is an overall indicator of the past 30 days Abuse
of psychological distress, whereas MDE is defined as a The prevalence of a MDE in 2010 was 6.8% of per-
period of at least 2 weeks when a person experienced a sons age 18 or older, or 15.5 million adults, with at least
depressed mood or loss of interest or pleasure in daily one MDE in the past year. The number of adults who
activities and had symptoms that met the criteria for a had past year MDE was 6.8%. Even then, the past year

Fig. 7. Serious mental illness, psychological distress, and nontherapeutic drug use, among persons age 18 and older, by age, 2010.
Source: Substance Abuse and Mental Health Services Administration. Results from the 2010 National Survey on Drug Use and Health: Men-
tal Health Findings. www.samhsa.gov/data/NSDUH/2k10MH_Findings/2k10MHResults.pdf (171) Access date 2/23/2012

ES20 www.painphysicianjournal.com
 Opioid Epidemic in the United States

prevalence of MDE in 2010 was lower for those age 50 abuse in the past year was more likely than those with
or older (5.6%) compared with rates among persons MDE to have used an illicit drug in the past year (22.0%
age 18 to 25 (8.2%) and those age 26 to 49 (7.5%). versus 7.9%) (171). A similar pattern was observed for
However, the past year prevalence of MDE was higher specific types of past year illicit drug use, such as mari-
among adult females than among adult males, 8.4% juana and the nonmedical use of prescription-type psy-
versus 5.1%. In addition, among women, past year chotherapeutics. Figure 8 illustrates substance abuse in
MDE rates were higher with 11.3% for 18 to 25 year adults by MDE.
olds, 9.2 for 26 to 49 year olds compared with those of The prevalence of a MDE in youths age 12 to 17 in
50 or older with only 6.7%. Further, the prevalence of 2010 showed that 1.9 million (8.9%) reported at least
MDE also varied by race and ethnicity with the highest one MDE during the past year. Among youths age 12 to
rate among persons reporting 2 or more races (10.8%), 17, the past year prevalence of MDE ranged from 3.3%
while rates for single race groups were 7.3% among among 12-year-olds to 10.9% among those age 16, and
whites, 5.6% among Hispanics, 7.7% among Ameri- 10.3% among those age 17 (171).
can Indians or Alaska Natives, 5.8% among blacks, and Among youths with MDE age 12 to 17, 37.2%
3.8% among Asians. had used illicit drugs in 2010, in contrast to 37.4% in
In addition, in 2010 the past prevalence of MDE 2008. This was higher than the 17.8% of youths in the
with severe impairment for adults age 18 or older was past year that did not have a MDE but had used illicit
higher among unemployed persons (9.3%) than among drugs. This pattern, however, was similar to specific
persons employed full time (5.4%). types of illicit drug use including marijuana and the
In 2010, an adult age 18 or older with a combina- nonmedical use of prescription-type psychotherapeu-
tion of a MDE and substance use and dependence or tics (171).

Fig. 8. Substance dependence or abuse among adults age 18 or older, by major depressive episode in the past years, 2010.
Source: Substance Abuse and Mental Health Services Administration. Results from the 2010 National Survey on Drug Use and Health:
Mental Health Findings. www.samhsa.gov/data/NSDUH/2k10MH_Findings/2k10MHResults.pdf (171) Access date 2/23/2012

www.painphysicianjournal.com ES21
 Pain Physician: Opioid Special Issue July 2012; 15:ES9-ES38

3.0 Where Do Non-Therapeutic Drugs 4.0 Escalating Use Of Therapeutic

Come From? Opioids
Among persons aged 12 or older in 2009-2010 who The escalating use of therapeutic opioids, specifi-
used pain relievers nonmedically in the past 12 months, cally in high doses over long periods of time or even
55% obtained pain relievers from a friend or relative for lifetime use of long-acting drugs, and the combination
free (170). Among the remaining 45%, 11.4% bought of long and short-acting drugs continue to have seri-
them from a friend or relative (which was significantly ous consequences for costs of health care and economic
higher than the 8.9% from 2007-2008), and 4.8% es- stability.
sentially stole them from a friend or relative (Fig. 9). The data overwhelmingly suggest that the in-
However, only one in 6 or 17.3% indicated that they creased supply of opioids, high medical users, doctor
received the drugs through a prescription from one shoppers, and patients with multiple comorbid factors
doctor, while only 4.4% received pain relievers from a contribute to the majority of fatalities. The quadrupled
drug dealer or other stranger, and 0.4% bought them sales of opioid analgesics between 1999 and 2010 are
on the Internet, with no significant changes from 2007 a perfect example of the therapeutic opioid explosion.
to 2008. The data on sales and distribution of opioids show an
Even more striking is the fact that in 2009-2010, increase from 96 mg morphine equivalents per person
41.5% of past year methamphetamine users reported in the United States in 1997 to 710 mg per person in
that they obtained the methamphetamine they used 2010 (34,153). This has been estimated to be the equiv-
most recently for free from a friend or relative, with alent of 7.1 kg of opioid medication per 10,000 persons
an additional 30.7% buying it from a friend or relative or enough to supply every adult American with 5 mg
(170). of hydrocodone every 6 hours for 45 days. Sales of hy-

Note: Totals may not sum to 100% because of rounding or because

suppressed estimates are not shown.

One took them from a friend or relative without asking

Fig. 9. Source where pain relievers were obtained for most recent nonmedical use among past year users age 12 or older: 2009-2010.
Source: Substance Abuse and Mental Health Services Administration. Results from the 2010 National Survey on Drug Use and Health: Mental
Health Findings. www.samhsa.gov/data/NSDUH/2k10MH_Findings/2k10MHResults.pdf (171) Access date 2/23/2012

ES22 www.painphysicianjournal.com
 Opioid Epidemic in the United States

drocodone have increased by 280% from 1997 to 2007, oids exceeded 256 million in the United States in 2009,
whereas methadone usage has increased 1,293% and with 234 million prescriptions for immediate-release
oxycodone usage by 866%, as illustrated in Table 5 (32). (IR) opioids and 22.9 million for extended-release (ER)
The estimated number of prescriptions filled for opi- opioids with significant increases from 21.3 million for

Table 5. Retail sales of opioid medications (grams of medication) from 1997 to 2007.
% of
Change
Drug 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 from
1997
692,675 964,982 1,428,840* 1,892,691 2,649,559 3,683,881 4,730,157 5,362,815 6,621,687 7,228,219
Methadone 518,737 1293%
(34%) (39%) (48%) (32%) (40%) (39%) (28%) (13%) (23%) (9%)

6,579,719 9,717,600 15,305,913 19,927,286 22,376,892 26,655,152 29,177,530 30,628,973 37,034,220 42,977,043
Oxycodone 4,449,562 866%
(48%) (48%) (58%) (30%) (12%) (19%) (9%) (5%) (21%) (16%)

90,618 107,141 146,612* 186,083 242,027 317,200 370,739 387,928 428,668 463,340
Fentanyl Base 74,086 525%
(22%) (18%) (37%) (27%) (30%) (31%) (17%) (5%) (11%) (8%)

260,009 292,506 346,574* 400,642 473,362 579,372 655,395 781,287 901,663 1,011,028
Hydromorphone 241,078 319%
(8%) (12%) (18%) (16%) (18%) (22%) (13%) (19%) (15% (12%)

10,389,503 12,101,621 14,118,637 15,594,692 18,822,619 22,342,174 24,081,900 25,803,543 29,856,368 32,969,527
Hydrocodone 8,669,311 280%
(20%) (16%) (17%) (10%) (21%) (19%) (8%) (7%) (16%) (10%)

6,408,322 6,804,935 7,807,511 8,810,700 10,264,264 12,303,956 14,319,243 15,054,846 17,507,148 19,051,426
Morphine 5,922,872 222%
(8%) (6%) (15%) (13%) (16%) (20%) (16%) (5%) (16%) (9%)

26,018,054 23,917,088 23,474,865* 23,032,641 22,633,733 21,865,409 20,264,555 18,960,038 18,762,919 18,840,329
Codeine 25,071,410 -25%
(4%) (-8%) (-2%) (-2%) (-2%) (-3%) (-7%) (-6%) (-1%) (0.4%)
Meperidine 5,834,294 5,539,592 5,494,898* 5,450,204 5,412,389 5,239,932 4,856,644 4,272,520 4,160,033 3,936,179
5,765,954 -32%
(Pethidine) (1%) (-5%) (-1%) (-1%) (-1%) (-3%) (-7%) (-12%) (-3%) (-5%)

56,273,194 59,445,465 35,962,089.84 75,294,939 82,874,845 92,987,076 98,456,163 101,251,950 115,272,706 126,477,091
Total 50,713,010 149%
(11%) (6%) (15%) (11%) (10%) (12%) (6%) (6%) (14%) (10%)

Number in parenthesis is percentage of change from previous year.

* For year 2000 data is not available, the average of 1999 and 2001 was taken.
Source: www.deadiversion.usdoj.gov/arcos/retail_drug_summary/index.html Access date: 8/25/2010
Source for 2007 data - www.justice.gov/ndic/pubs33/33775/dlinks.htm
Adapted from: Manchikanti L, et al. Therapeutic use, abuse, and nonmedical use of opioids: A ten-year perspective. Pain Physician 2010; 13:401-435 (32).

ER Opioids IR Opioids

250 233.8 234

223.9
211.1
199.9
179.9 188.6
200 171.3 174.8
164.8
TRx (millions)

150

100

50 17.4 19.4 21.3 22.9 22.9

9.3 11.6 12.7 14.7 16

0
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009
Year

Fig. 10. Total number of prescriptions dispensed for ER/LA and IR opioids from U. S. outpatient retail pharmacies, year 2000
– 2009 (173).
Source: SDI, Vector One ®: National (174).

www.painphysicianjournal.com ES23
 Pain Physician: Opioid Special Issue July 2012; 15:ES9-ES38

ER opioids and from 223.9 million for IR opioids from of the global consumption of morphine, fentanyl, and
2007 as illustrated in Figure 10 (172-174). The data are oxycodone registered in 2009 occurring in Australia,
even more compelling when compared from 2002 to Canada, New Zealand, the United States and several
2009 with an increase from 9.3 million for ER opioids to European countries (60,85).
22.9 million, a 146% increase, and from 164.8 million Another World Health Organization (WHO) report
to 234 million for IR opioids, a 42% increase with an (87) showed that based on the statistics from the In-
annual increase of 21% for ER opioids and 6% for IR ternational Narcotics Control Board (INCB) in 2003,
opioids. Most prescriptions were for hydrocodone and 6 developed countries accounted for 79% of global
oxycodone-containing products (84.9%) and issued for morphine consumption, whereas developing countries
short treatment courses, 19.1% for less than 2 weeks, which represent 80% of the world population account-
65.4% for 2-3 weeks. Of these, however, approximately ed for only about 6% of global morphine consumption.
12% of the prescriptions were issued to those aged 10 In addition, the most recent data showed that in 2007,
to 29 years. This may signal a potential problem for this 6 developed countries reported the highest level of
population, as this is also the population most likely to morphine consumption and 132 of the 160 signatory
abuse drugs and develop addictions (172). In addition, countries that require reporting of consumption were
the data also illustrates an 8-fold increase in stimulant below the global mean as illustrated in Fig. 13. This sim-
prescriptions from 1991 to 2009 as illustrated in Fig. 11. ply illustrates that millions of patients with moderate to
Table 6 illustrates hydrocodone with acetamino- severe pain caused by different diseases and conditions
phen being the number one prescription from 2006 may not be getting treatment to alleviate their suffer-
through 2011 (175). However, narcotic analgesics con- ing in some countries, while more of them are receiving
stitute number 4 in the proportion of patients treated it in other countries such as the United States, which
in selected therapies with hypertension, topping at 42.4 uses 99% of the world’s supply of hydrocodone and
million and narcotic analgesics at 15.6 million, consti- 83% of the world’s oxycodone (176-178).
tuting number 10 in spending in leading therapy areas Gram for gram, people in the United States con-
with oncologicals constituting 23.2 billion and narcotic sume more narcotic medication than any other nation
analgesics constituting 8.3 billion in 2011 as illustrated worldwide. The International Narcotic Control Board,
in Tables 7 and 8 and Fig. 12 (175). a division of the United States, estimates global phar-
The United Nations Office on Drugs and Crime, in maceutical companies produce more than 75 tons a
an evaluation of the world supply of opioid, shows 90% year of oxycodone, compared with 11.5 tons in 1999,

*excludes modafinil and atomoxetine products

Fig. 11. Projected number of prescriptions for stimulants* dispensed by U.S. retail pharmacies, 1991-2009.
Source: SDI, Vector One ®: National (174).

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 Opioid Epidemic in the United States

Table 6. Top medicines by prescriptions.

DISPENSED PRESCRIPTIONS MN 2007 2008 2009 2010 2011
Total US Market 3,825 3,866 3,949 3,993 4,024

1 Hydrocodone/acetaminophen 120.9 125.5 129.4 132.1 136.7

2 Levothyroxine sodium 97.4 98.9 100.2 103.2 104.7
3 Simvastatin 49.0 68.0 84.1 94.4 96.8
4 Lisinopril 71.5 77.2 83.0 87.6 88.8
5 Amlodipine besylate 40.8 46.0 52.1 57.8 62.5
6 Omeprazole (RX) 27.7 35.8 45.6 53.5 59.4
7 Metformin HCL 49.2 51.6 53.8 57.0 59.1
8 Azithromycin 47.1 51.9 54.7 53.6 56.2
9 Amoxicillin 54.0 51.3 52.9 52.4 53.8
10 Alprazolam 41.4 43.3 45.3 47.7 49.1
11 Hydrochlorothiazide 48.5 48.5 47.9 47.8 48.1
12 Zolpidem tartrate 34.5 39.1 42.7 43.7 44.6
13 Atorvastatin 65.8 58.5 51.7 45.3 43.3
14 Furosemide 44.7 44.4 43.8 43.6 42.3
15 Oxycodone/acetaminophen 31.3 33.6 36.7 37.9 38.8
16 Fluticasone 23.9 26.2 30.1 34.8 38.4
17 Citalopram HBR 18.1 22.6 27.3 32.2 37.8
18 Metoprolol tartrate 43.5 38.4 41.1 38.9 37.8
19 Sertraline HCL 33.4 33.7 34.8 36.2 37.6
20 Metoprolol succinate 33.0 41.5 26.9 33.0 34.5
21 Warfarin sodium 34.4 34.9 35.7 35.6 33.9
22 Tramadol HCL 20.6 23.3 25.5 28.0 33.9
23 Potassium 36.7 35.8 35.2 34.7 33.7
24 Prednisone 25.9 27.1 27.8 28.7 33.7
25 Atenolol 45.0 42.0 39.5 36.4 33.4

Source: IMS Health, National Prescription Audit, Dec. 2011 (175).

Notes: Report reflects prescription-bound products including insulins and excluding other products such as OTC. Table shows lead-
ing active-ingredients or ingredient fixed-combinations, and includes those produced by both branded and generic manufacturers.
Includes all prescriptions dispensed through retail pharmacies - including independent and chain drug stores, food store pharmacies
and mail order as well as long-term care facilities. Prescription counts are not adjusted for length of therapy. 90-day and 30-day pre-
scriptions are both counted as one prescription.

Updated February 17, 2012.

of which more than 80% of is consumed in the United trates that from 1999 to 2002, 4.2% of U.S. adults re-
States. The International Narcotics Board also reports ported the use of opioid analgesics for pain within the
that U.S. demand for hydrocodone, the most commonly past month (179). In a report of opioid use in one of
prescribed opioid, is about 27.4 million grams annually the states in the United States (Utah) (180), the data
compared to 3,237 grams for Britain, France, Germany, showed that 20.8% of adults had been prescribed an
and Italy combined (61,177,178). opioid in the last year and that 29.1% of these prescrip-
Caudill-Slosberg et al (165) in one of the earliest tions were for long-term pain. Sullivan et al (181) also
evaluations demonstrated that opioid use doubled showed over a 6 year period that the proportion of
from 8% in 1980 to 16% in 2000. The data also illus- enrollees receiving opioids with a diagnosis of chronic

www.painphysicianjournal.com ES25
 Pain Physician: Opioid Special Issue July 2012; 15:ES9-ES38

Source: IMS Health, LifeLink, Dec 2011

Fig. 12. Treated patients in selected therapy.

Table 7. Spending based on the therapeutic class.

SPENDING $BN 2007 2008 2009 2010 2011 SPENDING $BN 2007 2008 2009 2010 2011
Total US Market 280.5 285.7 300.7 308.6 319.9 Platelet
12 Aggregation 5.0 5.7 6.5 7.1 7.8
1 Oncologics 18.1 19.7 21.5 22.3 23.2 Inhibitors

2 Respiratory Agents 15.1 16.0 18.1 19.3 21.0 13 Angiotensin II

6.5 7.6 8.6 8.7 7.6
Inhibitors
3 Lipid Regulators 19.4 18.1 18.6 18.8 20.1
14 Multiple Sclerosis 3.4 4.1 5.0 5.8 7.1
4 Antidiabetics 12.2 13.6 15.8 17.7 19.6
15 Vaccines (Pure,
5.9 5.0 4.7 5.7 6.3
5 Antipsychotics 12.8 14.3 14.7 16.2 18.2 Comb, Other)

Autoimmune 16 Anti-Epileptics 10.0 11.1 6.9 5.6 5.9

6 7.6 8.6 9.7 10.6 12.0
Diseases
17 Erythropoietins 4.1 4.5 4.7 4.8 5.2
7 Antidepressant 11.7 11.7 11.5 11.6 11.0
18 Immunostimulating
8.4 6.9 6.3 6.1 5.1
8 HIV Antivirals 6.2 7.1 8.2 9.3 10.3 Agents

9 Anti-Ulcerants 14.6 14.2 14.1 11.9 10.1 19 Hormonal

4.1 4.1 4.1 4.2 4.5
Contraceptives
Narcotic
10 6.7 7.3 8.0 8.4 8.3 Antivirals, excl.
Analgesics 20 3.6 3.9 4.8 3.2 3.7
Anti-HIV
11 ADHD 4.0 4.7 5.8 6.7 7.9

Source: IMS Health, National Prescription Audit, Dec. 2011 (175).

Notes:
Therapy areas are based on proprietary IMS Health definitions. Report reflects prescription-bound products including insulins and excluding
other products such as OTC. Includes all prescriptions dispensed through retail pharmacies - including independent and chain drug stores, food
store pharmacies and mail order as well as long-term care facilities. Prescription counts are not adjusted for length of therapy. 90-day and 30-day
prescriptions are both counted as one prescription.

Updated February 17, 2012.

ES26 www.painphysicianjournal.com
 Opioid Epidemic in the United States

Table 8. Top therapeutic classes by prescriptions.

DISPENSED PRESCRIPTIONS MN 2007 2008 2009 2010 2011

Total US Market 3,825 3,866 3,949 3,993 4,024

1 Antidepressants 237 241 247 254 264

2 Lipid Regulators 233 242 254 260 260
3 Narcotic Analgesics 231 239 241 244 238
4 Antidiabetics 165 166 169 172 173
5 Ace Inhibitors (Plain & Combo) 159 163 166 168 164
6 Beta Blockers (Plain & Combo) 162 164 163 162 161
7 Respiratory Agents 147 147 152 153 153
8 Anti-Ulcerants 134 139 146 147 150
9 Diuretics 137 135 132 131 128

10 Anti-Epileptics 102 110 116 122 128

11 Tranquillizers 98 101 104 108 111
12 Thyroid Preparations 103 104 105 107 110
13 Calcium Antagonists (Plain & Combo) 87 90 93 96 98
14 Antirheumatic Non-Steroid 90 91 92 93 97
15 Hormonal Contraceptives 94 94 93 91 90
16 Angiotensin II Inhibitors 83 86 85 84 86
17 Broad Spectrum Penicillins 77 74 77 76 77
18 Macrolides & Similar Type Antibiotics 63 66 69 67 69
19 Hypnotics & Sedatives 58 60 63 63 63
20 Vitamins & Minerals 60 59 58 58 60
Source: IMS Health, National Prescription Audit, Dec. 2011 (175).
Appendix notes:
Therapy areas are based on proprietary IMS Health definitions. Report reflects prescription-bound products including insulins
and excluding other products such as OTC. Includes all prescriptions dispensed through retail pharmacies - including indepen-
dent and chain drug stores, food store pharmacies and mail order as well as long-term care facilities. Prescription counts are not
adjusted for length of therapy. 90-day and 30-day prescriptions are both counted as one prescription.

Updated February 17, 2012.

non-cancer pain and opioid prescriptions increase. Opi- management settings. Volkow et al (172) showed that
oids are also used commonly in combination with seda- only a small proportion of prescriptions were from
tive hypnotics. Vogt et al (182) in an evaluation of anal- pain clinics or specialists from anesthesiology in 2009.
gesic usage for low back pain and its impact on health Moreover, Deyo et al (31) illustrated that approxi-
care costs and service use showed that in 2001, a total mately 20% of patients in primary care settings were
of $1.4 million was spent on opioids, which constituted long-time opioid users with 61% receiving a course
68% of prescriptions for analgesics. of opioids. In young veterans, Wu et al (189) showed
The data from reports and pain management set- that prevalence of chronic opioid use increased from
tings is disconcerting. Over 90% of patients received 3% in 2003 to 4.5% in 2007. Patients on average were
opioids for chronic pain management (32,169,172,183- exposed to 2 different opioids and had 3 different
188). Even more alarming, however, is the fact that opioid prescribers. Not surprisingly, 80% of the opioid
the majority of the prescriptions are from outside pain prescriptions during the study were prescribed by pri-

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 Pain Physician: Opioid Special Issue July 2012; 15:ES9-ES38

Fig. 13. Global morphine consumption in 2007 (mg/capita).

Source: International Narcotics Control Board, United Nations data. Graphic created by the Pain and Policy Study Group, University of Wiscon-
sin/WHO Collaborating Center, 2009.

IR Opioid Prescribers ER/LA Opioid Prescribers

Fig. 14. Total number of prescriptions dispensed in the U.S. by top 10 prescribing specialties for IR and ER/ LA opioids, year
2009 (173). Source: SDI, Vector One ®: National (174).

mary care providers, and less than 1% was from pain cialists constituting 2.7% (173,174). In contrast, for ER or
specialists. long-acting opioids in 2009, anesthesiologists constituted
In fact, the data illustrates that in 2009 (Fig. 14). among 13.8% and physical medicine and rehabilitation constitut-
the top 10 specialties of those prescribing immediate re- ed 9.3%, with general practitioners, family medical doctors,
lease opioids were general practitioners/family medicine osteopaths, and internal medicine specialists still dominat-
26.7%, internal medicine 15.4%, anesthesiologists consti- ing the field with 27% and 16.8%, in essence exceeding
tuting 3.2%, and physical medicine and rehabilitation spe- their prescriptions of immediate release opioids (173,174).

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 Opioid Epidemic in the United States

5.0 Relationship of Escalating Opioid

Use and Adverse Consequences combined (190-192). Thus, it has been concluded that
opioid analgesics contributed to fatalities based on
While numerous adverse effects have been re- opioid abuse and increasing doses, doctor shopping,
ported, ever increasing opioid related fatalities, in- and other aspects of drug abuse as illustrated in Fig.
cluding drug poisoning deaths, are crucial. In the 16 (160). The data from emergency department visits
United States, in 2008, one or more prescription drugs sadly illustrate that opioids, sedatives, and non-pre-
were involved in 20,044 of the 27,153 deaths with a scription sleep aides are often taken more than pre-
specified drug. Opioid pain relievers were involved in scribed or solely for the feeling they cause, and that
14,800 drug overdose deaths, compared to 11,500 of this trend is steadily increasing (170).
27,500 fatal unintended drug overdose deaths in 2007 The Centers for Disease Control and Prevention
– an increase of 3,300 in just one year (160). Alarm- (CDC) (34) also reported the percentage of prescription
ingly, in 2007 there were more opioid analgesic over- drug overdoses by risk group in the United States. This re-
dose deaths than overdoses involving heroin and co- port showed that approximately 80% of prescribed low-
caine combined (Fig. 15). In addition, during the same doses (less than 100 mg of morphine equivalent dose per
time frame, drug-related suicides also increased, with day – considered as high dose by many) were by a single
opioid analgesics being involved in roughly 3,000 of practitioner, accounting for an estimated 20% of all pre-
the 8,400 overdose deaths in the United States in 2007 scription overdoses (Fig. 17). In contrast, among the re-
that were suicide or of undetermined intent (190). maining 20% of patients, 10% of prescribed high doses
Complicating these grave statistics, for every uninten- (greater than 100 mg morphine equivalent dose per day)
tional overdose death related to an opioid analgesic, (193-195) per day of opioids by single prescribers account
9 are admitted for substance abuse treatment, 35 visit for an estimated 40% of the prescription opioid overdos-
emergency departments, 161 report drug abuse or de- es (131,195). The remaining 10% of patients seeing mul-
pendence, and 461 report non-medical uses of opioid tiple doctors and typically involved in drug diversion con-
analgesics (34). Not surprisingly, in 2007, non-suicidal tribute to 40% of overdoses (152). Furthermore, among
drug poisoning deaths exceeded both motor vehicle persons who died of opioid overdoses, a significant pro-
traffic and suicide deaths in 20 states, with data from portion did not have a prescription in their records for
Ohio illustrating that the number of deaths from un- the opioid that killed them; in West Virginia, Utah, and
intentional drug poisoning surpassed the numbers of Ohio, 25% to 66% of those who died of pharmaceutical
deaths from both suicide and motor vehicle crashes overdose used opioids originally prescribed to someone

Fig. 15. Deaths from unintentional drug overdoses in the United States according to major type of drug, 1999-2007.
Source: Centers for Disease Control and Prevention. Unintentional Drug Poisoning in the United States. July 2010. http://www.cdc.gov/Home-
andRecreationalSafety/pdf/poison-issue-brief.pdf (190).

www.painphysicianjournal.com ES29
 Pain Physician: Opioid Special Issue July 2012; 15:ES9-ES38

else (152,192,196).
The responsible opioid prescription community
considers that the adverse consequences of appropri-
ately prescribed and used opioids are least considered,
as the blame is placed predominantly on abuses and
overuses (49,71,116-119). Consequently, it is coupled
with a lack of evidence regarding long-term benefits
and ample evidence that the increased prescription of
opioids is fueling an epidemic of addiction and over-
dose deaths. This crisis is rooted in a lack of education
and misinformation, leading to overprescribing and a
tendency to focus on ineffective strategies (49,71,197-
199). In fact, the majority of cases involving injury and
death occur in people using opioids exactly as pre-
scribed, not just those misusing or abusing them (71).
Even more importantly, most studies indicate that pa-
tients on long-term opioid therapy are unlikely to stop
even if analgesia and function are poor and safety is-
sues arise. Frequently, despite good relief and improve-
ment in function with modalities other than opioids in-
cluding interventional techniques and surgery, patients
* Age-adjusted rates per 100,000 population for OPR deaths, crude continue on opioids (200-215).
rates per 10,000 population for OPR abuse treatment admissions,
and crude rates per 10,000 population for kilograms of OPR sold.
Even though there is no evidence to support the
previous teaching that long-acting opioids can provide
Fig. 16. Rates of opioid pain reliever overdose death, opioid better analgesia, and less risk for abuse than immediate
pain relief treatment admissions, and kilograms of opioid release products (32,71,96,100,103,107,116-119,216),
pain relievers sold – United States, 1999-2010. the use of higher doses, with a combination of short-
Source: Centers for Disease Control and Prevention. Vital signs:
Overdoses of prescription opioid pain relievers – United States, acting and long-acting opioids, continues to escalate.
1999-2008. MMWR. Morb. Mortal Wkly. Rep. 60, 1487-1492 Thus, it is believed that commencing long-acting opioid
(2011) (160). therapy is often the starting point for high dose opi-

100%
10%
10% Patients seeing multiple
80% 40% doctors and typically
involved in drug diversion
60% Patients seeing one doctor,
high dose
40% 80% 40%
Patients seeing one doctor,
20% low dose
20%
0%
Patients Overdoses

Fig. 17. Percentage of patients and prescription drug overdoses, by risk group – United States.
Source: Centers for Disease Control and Prevention. CDC grand rounds: Prescription drug overdoses – a U.S. epidemic. MMWR. Morb. Mor-
tal Wkly. Rep. 61, 10-13 (2012) (34).

ES30 www.painphysicianjournal.com
 Opioid Epidemic in the United States

oid therapy, a practice that growing evidence suggests opioid abuse in chronic pain has been highly prevalent,
is harmful to patients and increases the black market along with illicit drug usage in addition to misuse or
availability of opioids through diversion (71,217-222). abuse of therapeutic opioids (32,143-152,183-188).
Multiple studies in the literature (23,32,37,46-
49,223-236) have reported an association between opi-
Conclusion
oid prescribing and overall health status, with increased What emerges from the available data utilized
disability, medical costs, subsequent surgery, and con- in this review is the conclusion that over the past 20
tinued or late opioid use. Overall, the epidemiologic years there has been an escalation of the therapeutic
studies are less positive with regards to improvement use of opioids and other psychotherapeutics as well as
in function and quality of life with opioids in chronic their abuse and nonmedical use. As a consequence of
pain patients (110,116-119,170,232,237). In fact, in an the fact that hydrocodone has become the number one
epidemiologic study from Denmark (23) where opioids prescribed medication in America, it is not difficult to
are prescribed liberally for chronic pain, it was dem- see the significant impact that this has had on the over-
onstrated that in patients receiving opioids, pain was all patterns of abuse and nonmedical use, particularly
worse, health care utilization was higher, and activ- since the illicit use of prescribed psychotherapeutics (in-
ity levels were lower compared to a matched cohort cluding opioids, which are currently at the top of that
of chronic pain patients not using opioids. This study list) now overshadows the use of nonprescription illicit
suggested that when opioids are prescribed liberally, drugs. Drug dealers are no longer the primary source
even if some patients benefit, the overall population of illicit drugs. Our greatest enemy is now inappropri-
does not. Another study (33) also reported worse pain, ate prescribing patterns, based on a lack of knowledge,
higher health care utilization, and lower activity levels perceived safety, and undertreatment of pain.
in opioid-treated patients compared to matched cohort
of chronic pain patients not using opioids. Sjøgren et al
Acknowledgments
(49) in a population-based cohort study on chronic pain The authors wish to thank Sekar Edem for assis-
and the role of opioids, showed that the odds of recov- tance in the search of the literature, Tom Prigge, MA,
ery from chronic pain were almost 4 times higher among and Alvaro Gómez, MA, for manuscript review, and
individuals not using opioids compared with individuals Tonie M. Hatton and Diane E. Neihoff, transcription-
using opioids. In addition, they also showed that use of ists, for their assistance in preparation of this manu-
strong opioids was associated with poor health-related script. We would like to thank the editorial board of
quality of life, and higher risk of death. In addition, Pain Physician for review and criticism in improving the
manuscript

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EXHIBIT B
Am J Public Health. 2009 February; 99(2): 221–227.
doi: 10.2105/AJPH.2007.131714
PMCID: PMC2622774

The Promotion and Marketing of

OxyContin: Commercial Triumph, Public
Health Tragedy
Art Van Zee, MD
Author information ► Article notes ► Copyright and License information ►
This article has been cited by other articles in PMC.
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Abstract
I focus on issues surrounding the promotion and marketing of controlled drugs and their regulatory
oversight. Compared with noncontrolled drugs, controlled drugs, with their potential for abuse and
diversion, pose different public health risks when they are overpromoted and highly prescribed. An in-
depth analysis of the promotion and marketing of OxyContin illustrates some of the associated issues.

Modifications of the promotion and marketing of controlled drugs by the pharmaceutical industry and an
enhanced capacity of the Food and Drug Administration to regulate and monitor such promotion can have a
positive impact on the public health.

CONTROLLED DRUGS, WITH their potential for abuse and diversion, can pose public health risks that
are different from—and more problematic than—those of uncontrolled drugs when they are overpromoted
and highly prescribed. An in-depth analysis of the promotion and marketing of OxyContin (Purdue Pharma,
Stamford, CT), a sustained-release oxycodone preparation, illustrates some of the key issues. When Purdue
Pharma introduced OxyContin in 1996, it was aggressively marketed and highly promoted. Sales grew
from $48 million in 1996 to almost $1.1 billion in 2000.1 The high availability of OxyContin correlated
with increased abuse, diversion, and addiction, and by 2004 OxyContin had become a leading drug of
abuse in the United States.2

Under current regulations, the Food and Drug Administration (FDA) is limited in its oversight of the
marketing and promotion of controlled drugs. However, fundamental changes in the promotion and
marketing of controlled drugs by the pharmaceutical industry, and an enhanced capacity of the FDA to
regulate and monitor such promotion, can positively affect public health.

OxyContin's commercial success did not depend on the merits of the drug compared with other available
opioid preparations. The Medical Letter on Drugs and Therapeutics concluded in 2001 that oxycodone
offered no advantage over appropriate doses of other potent opioids.3 Randomized double-blind studies
comparing OxyContin given every 12 hours with immediate-release oxycodone given 4 times daily showed
comparable efficacy and safety for use with chronic back pain4 and cancer-related pain.5,6 Randomized
double-blind studies that compared OxyContin with controlled-release morphine for cancer-related pain
also found comparable efficacy and safety.7–9 The FDA's medical review officer, in evaluating the efficacy
of OxyContin in Purdue's 1995 new drug application, concluded that OxyContin had not been shown to
have a significant advantage over conventional, immediate-release oxycodone taken 4 times daily other
than a reduction in frequency of dosing.10 In a review of the medical literature, Chou et al. made similar
conclusions.11

The promotion and marketing of OxyContin occurred during a recent trend in the liberalization of the use
of opioids in the treatment of pain, particularly for chronic non–cancer-related pain. Purdue pursued an
“aggressive” campaign to promote the use of opioids in general and OxyContin in particular.1,12–17 In 2001
alone, the company spent $200 million18 in an array of approaches to market and promote OxyContin.

Go to:

PROMOTION OF OXYCONTIN
From 1996 to 2001, Purdue conducted more than 40 national pain-management and speaker-training
conferences at resorts in Florida, Arizona, and California. More than 5000 physicians, pharmacists, and
nurses attended these all-expenses-paid symposia, where they were recruited and trained for Purdue's
national speaker bureau.19(p22) It is well documented that this type of pharmaceutical company symposium
influences physicians’ prescribing, even though the physicians who attend such symposia believe that such
enticements do not alter their prescribing patterns.20

One of the cornerstones of Purdue's marketing plan was the use of sophisticated marketing data to influence
physicians’ prescribing. Drug companies compile prescriber profiles on individual physicians—detailing
the prescribing patterns of physicians nationwide—in an effort to influence doctors’ prescribing habits.
Through these profiles, a drug company can identify the highest and lowest prescribers of particular drugs
in a single zip code, county, state, or the entire country.21 One of the critical foundations of Purdue's
marketing plan for OxyContin was to target the physicians who were the highest prescribers for opioids
across the country.1,12–17,22 The resulting database would help identify physicians with large numbers of
chronic-pain patients. Unfortunately, this same database would also identify which physicians were simply
the most frequent prescribers of opioids and, in some cases, the least discriminate prescribers.

A lucrative bonus system encouraged sales representatives to increase sales of OxyContin in their
territories, resulting in a large number of visits to physicians with high rates of opioid prescriptions, as well
as a multifaceted information campaign aimed at them. In 2001, in addition to the average sales
representative's annual salary of $55 000, annual bonuses averaged $71 500, with a range of $15 000 to
nearly $240 000. Purdue paid $40 million in sales incentive bonuses to its sales representatives that year.19

From 1996 to 2000, Purdue increased its internal sales force from 318 sales representatives to 671, and its
total physician call list from approximately 33 400 to 44 500 to approximately 70 500 to 94 000
physicians.19 Through the sales representatives, Purdue used a patient starter coupon program for
OxyContin that provided patients with a free limited-time prescription for a 7- to 30-day supply. By 2001,
when the program was ended, approximately 34 000 coupons had been redeemed nationally.19

The distribution to health care professionals of branded promotional items such as OxyContin fishing hats,
stuffed plush toys, and music compact discs (“Get in the Swing With OxyContin”) was unprecedented for a
schedule II opioid, according to the Drug Enforcement Administration.19

Purdue promoted among primary care physicians a more liberal use of opioids, particularly sustained-
release opioids. Primary care physicians began to use more of the increasingly popular OxyContin; by
2003, nearly half of all physicians prescribing OxyContin were primary care physicians.19 Some experts
were concerned that primary care physicians were not sufficiently trained in pain management or addiction
issues.23 Primary care physicians, particularly in a managed care environment of time constraints, also had
the least amount of time for evaluation and follow-up of patients with complicated chronic pain.
Purdue “aggressively” promoted the use of opioids for use in the “non-malignant pain market.”15(p187) A
much larger market than that for cancer-related pain, the non–cancer-related pain market constituted 86%
of the total opioid market in 1999.17 Purdue's promotion of OxyContin for the treatment of non–cancer-
related pain contributed to a nearly tenfold increase in OxyContin prescriptions for this type of pain, from
about 670 000 in 1997 to about 6.2 million in 2002, whereas prescriptions for cancer-related pain increased
about fourfold during that same period.19 Although the science and consensus for the use of opioids in the
treatment of acute pain or pain associated with cancer are robust, there is still much controversy in
medicine about the use of opioids for chronic non–cancer-related pain, where their risks and benefits are
much less clear. Prospective, randomized, controlled trials lasting at least 4 weeks that evaluated the use of
opioids for chronic, non–cancer-related pain showed statistically significant but small to modest
improvement in pain relief, with no consistent improvement in physical functioning.24–38 A recent review of
the use of opioids in chronic back pain concluded that opioids may be efficacious for short-term pain relief,
but longer-term efficacy ( > 16 weeks) is unclear.39

In the long-term use of opioids for chronic non–cancer-related pain, the proven analgesic efficacy must be
weighed against the following potential problems and risks: well-known opioid side effects, including
respiratory depression, sedation, constipation, and nausea; inconsistent improvement in functioning; opioid-
induced hyperalgesia; adverse hormonal and immune effects of long-term opioid treatment; a high
incidence of prescription opioid abuse behaviors; and an ill-defined and unclarified risk of iatrogenic
addiction.40

MISREPRESENTING THE RISK OF ADDICTION

A consistent feature in the promotion and marketing of OxyContin was a systematic effort to minimize the
risk of addiction in the use of opioids for the treatment of chronic non–cancer-related pain. One of the most
critical issues regarding the use of opioids in the treatment of chronic non–cancer-related pain is the
potential of iatrogenic addiction. The lifetime prevalence of addictive disorders has been estimated at 3% to
16% of the general population.41 However, we lack any large, methodically rigorous prospective study
addressing the issue of iatrogenic addiction during long-term opioid use for chronic nonmalignant pain.42

In much of its promotional campaign—in literature and audiotapes for physicians, brochures and
videotapes for patients, and its “Partners Against Pain” Web site—Purdue claimed that the risk of addiction
from OxyContin was extremely small.43–49

Purdue trained its sales representatives to carry the message that the risk of addiction was “less than one
percent.”50(p99) The company cited studies by Porter and Jick,51 who found iatrogenic addiction in only 4 of
11 882 patients using opioids and by Perry and Heidrich,52 who found no addiction among 10 000 burn
patients treated with opioids. Both of these studies, although shedding some light on the risk of addiction
for acute pain, do not help establish the risk of iatrogenic addiction when opioids are used daily for a
prolonged time in treating chronic pain. There are a number of studies, however, that demonstrate that in
the treatment of chronic non–cancer-related pain with opioids, there is a high incidence of prescription drug
abuse. Prescription drug abuse in a substantial minority of chronic-pain patients has been demonstrated in
studies by Fishbain et al. (3%–18% of patients),53 Hoffman et al. (23%),54 Kouyanou et al. (12%),55 Chabal
et al. (34%),56 Katz et al. (43%),57 Reid et al. (24%–31%),58 and Michna et al. (45%).59 A recent literature
review showed that the prevalence of addiction in patients with long-term opioid treatment for chronic
non–cancer-related pain varied from 0% to 50%, depending on the criteria used and the subpopulation
studied.60

Misrepresenting the risk of addiction proved costly for Purdue. On May 10, 2007, Purdue Frederick
Company Inc, an affiliate of Purdue Pharma, along with 3 company executives, pled guilty to criminal
charges of misbranding OxyContin by claiming that it was less addictive and less subject to abuse and
diversion than other opioids, and will pay $634 million in fines.61
Although research demonstrated that OxyContin was comparable in efficacy and safety to other available
opioids,11,63 marketing catapulted OxyContin to blockbuster drug status. Sales escalated from $44 million
(316 000 prescriptions dispensed) in 1996 to a 2001 and 2002 combined sales of nearly $3 billion (over 14
million prescriptions).19

The remarkable commercial success of OxyContin, however, was stained by increasing rates of abuse and
addiction. Drug abusers learned how to simply crush the controlled-release tablet and swallow, inhale, or
inject the high-potency opioid for an intense morphinelike high.64 There had been some precedence for the
diversion and abuse of controlled-release opioid preparations. Purdue's own MS Contin had been abused in
the late 1980s in a fashion similar to how OxyContin was later to be; by 1990, MS Contin had become the
most abused prescription opioid in one major metropolitan area.65 Purdue's own testing in 1995 had
demonstrated that 68% of the oxycodone could be extracted from an OxyContin tablet when crushed.66

Opioid prescribing has had significant geographical variations. In some areas, such as Maine, West
Virginia, eastern Kentucky, southwestern Virginia, and Alabama, from 1998 through 2000, hydrocodone
and (non-OxyContin) oxycodone were being prescribed 2.5 to 5.0 times more than the national average. By
2000, these same areas had become high OxyContin-prescribing areas—up to 5 to 6 times higher than the
national average in some counties (Table 1).67 These areas, in which OxyContin was highly available, were
the first in the nation to witness increasing OxyContin abuse and diversion, which began surfacing in 1999
and 2000.23 From 1995 to 2001, the number of patients treated for opioid abuse in Maine increased 460%,
and from 1997 to 1999 the state had a 400% increase in the number of chronic hepatitis C cases reported.68
In eastern Kentucky from 1995 to 2001, there was a 500% increase in the number of patients entering
methadone maintenance treatment programs, about 75% of whom were OxyContin dependent (Mac Bell,
administrator, Narcotics Treatment Programs, Kentucky Division of Substance Abuse, written
communication, March 2002). In West Virginia, the first methadone maintenance treatment program
opened in August 2000, largely in response to the increasing number of people with OxyContin
dependence. By October 2003, West Virginia had 7 methadone maintenance treatment clinics with 3040
patients in treatment (M. Moore, Office of Behavioral Health Services, Office of Alcoholism and Drug
Abuse, West Virginia, written communication, March 16, 2004). In southwestern Virginia, the first
methadone maintenance treatment program opened in March 2000, and within 3 years it had 1400
admissions (E. Jennings, Life Center of Galax, Galax, Virginia, written communication, March 12, 2004).

TABLE 1
Distribution of OxyContin, Oxycodone (Excluding OxyContin), and Hydrocodone per 100 000
Population: Virginia, West Virginia, and Kentucky, 2000

With increasing diversion and abuse, opioid-related overdoses escalated. In southwest Virginia, the number
of deaths related to opioid prescriptions increased 830%, from 23 in 1997 to 215 in 2003 (William
Massello III, MD, assistant chief medical examiner, Office of Chief Medical Examiner, Western District,
Virginia Department of Health, written communication, January 12, 2007). The high availability of
OxyContin in these 5 regions seemed to be a simple correlate of its abuse, diversion, and addiction.

With the growing availability of OxyContin prescriptions, the once-regional problem began to spread
nationally. By 2002, OxyContin accounted for 68% of oxycodone sales.69 Lifetime nonmedical use of
OxyContin increased from 1.9 million to 3.1 million people between 2002 and 2004, and in 2004 there
were 615 000 new nonmedical users of OxyContin.70 By 2004, OxyContin had become the most prevalent
prescription opioid abused in the United States.2

The increasing OxyContin abuse problem was an integral part of the escalating national prescription opioid
abuse problem. Liberalization of the use of opioids, particularly for the treatment of chronic non–cancer-
related pain, increased the availability of all opioids as well as their abuse. Nationwide, from 1997 to 2002,
there was a 226%, 73%, and 402% increase in fentanyl, morphine, and oxycodone prescribing, respectively
(in grams per 100 000 population). During that same period, the Drug Abuse Warning Network reported
that hospital emergency department mentions for fentanyl, morphine, and oxycodone increased 641%,
113%, and 346%, respectively.71 Among new initiates to illicit drug use in 2005, a total of 2.1 million
reported prescription opioids as the first drug they had tried, more than for marijuana and almost equal to
the number of new cigarette smokers (2.3 million).72 Most abusers of prescription opioids get their diverted
drugs directly from a doctor's prescription or from the prescriptions of friends and family.73

In terms of illicit drug abuse, prescription opioids are now ahead of cocaine and heroin and second only to
marijuana.72 Mortality rates from drug overdose have climbed dramatically; by 2002, unintentional
overdose deaths from prescription opioids surpassed those from heroin and cocaine nationwide.74
Nationally, as well as regionally, the high availability of OxyContin and all prescription opioids was
correlated with high rates of abuse and diversion.

THE FOOD AND DRUG ADMINISTRATION

Under the Food, Drug, and Cosmetics Act and implementing regulations, the FDA regulates the advertising
and promotion of prescription drugs and is responsible for ensuring that prescription drug advertising and
promotion are truthful, balanced, and accurately communicated. There is no distinction in the act between
controlled and noncontrolled drugs regarding the oversight of promotional activities. Although regulations
require that all promotional materials for prescription drugs be submitted to the FDA for review when the
materials are initially disseminated or used, it is generally not required that these materials be approved by
the FDA prior to their use. The FDA has a limited number of staff for overseeing the enormous amount of
promotional materials. In 2002, for example, 39 FDA staff members were responsible for reviewing
roughly 34 000 pieces of promotional materials.19 This limited staffing significantly diminishes the FDA's
ability to ensure that the promotion is truthful, balanced, and accurately communicated.

In 1998, Purdue distributed 15 000 copies of an OxyContin video to physicians without submitting it to the
FDA for review, an oversight later acknowledged by Purdue. In 2001, Purdue submitted to the FDA a
second version of the video, which the FDA did not review until October 2002—after the General
Accounting Office inquired about its content. After its review, the FDA concluded that the video
minimized the risks from OxyContin and made unsubstantiated claims regarding its benefits to patients.19

When OxyContin entered the market in 1996, the FDA approved its original label, which stated that
iatrogenic addiction was “very rare” if opioids were legitimately used in the management of pain. In July
2001, to reflect the available scientific evidence, the label was modified to state that data were not available
for establishing the true incidence of addiction in chronic-pain patients. The 2001 labeling also deleted the
original statement that the delayed absorption of OxyContin was believed to reduce the abuse liability of
the drug.19 A more thorough review of the available scientific evidence prior to the original labeling might
have prevented some of the need for the 2001 label revision.

CONCLUSIONS
OxyContin appears to be as efficacious and safe as other available opioids and as oxycodone taken 4 times
daily.11,63 Its commercial success, fueled by an unprecedented promotion and marketing campaign, was
stained by escalating OxyContin abuse and diversion that spread throughout the country.2,75 The regions of
the country that had the earliest and highest availability of prescribed OxyContin had the greatest initial
abuse and diversion.23,67 Nationally, the increasing availability of OxyContin was associated with higher
rates of abuse, and it became the most prevalent abused prescription opioid by 2004.2

Compared with noncontrolled drugs, controlled drugs, with their potential for abuse and diversion, pose
different public health risks when overpromoted and highly prescribed. Several marketing practices appear
to be especially questionable.
The extraordinary amount of money spent in promoting a sustained-release opioid was unprecedented.
During OxyContin's first 6 years on the market, Purdue spent approximately 6 to 12 times more on
promoting it than the company had spent on promoting MS Contin, or than Janssen Pharmaceutical
Products LP had spent on Duragesic, one of OxyContin's competitors.19 Although OxyContin has not been
shown to be superior to other available potent opioid preparations,11,63 by 2001 it had become the most
frequently prescribed brand-name opioid in the United States for treating moderate to severe pain.19
Carefully crafted limits on the marketing and promotion of controlled drugs would help to realign their
actual use with the principles of evidence-based medicine.

Physicians’ interactions with pharmaceutical sales representatives have been found to influence the
prescribing practices of residents and physicians in terms of decreased prescribing of generic drugs,
prescribing cost, nonrational prescribing, and rapid prescribing of new drugs.76 Carefully crafted limits on
the promotion of controlled drugs by the pharmaceutical sales force and enhanced FDA oversight of the
training and performance of sales representatives would also reduce over- and misprescribing.

Although there are no available data for evaluating the promotional effect of free starter coupons for
controlled drugs, it seems likely that the over- and misprescribing of a controlled drug are encouraged by
such promotional programs and the public health would be well served by eliminating them.

The use of prescriber profiling data to influence prescribing and improve sales is imbedded in
pharmaceutical detailing. Very little data are publicly available for understanding to what extent this
marketing practice boosts sales. One market research report indicated that profiling improved profit
margins by as much as 3 percentage points and the initial uptake of new drugs by 30%.77 The use of
prescriber profiling data to target high-opioid prescribers—coupled with very lucrative incentives for sales
representatives—would seem to fuel increased prescribing by some physicians—perhaps the most liberal
prescribers of opioids and, in some cases, the least discriminate. Regulations eliminating this marketing
tool might decrease some potential overprescribing of controlled drugs.

The public health would be better protected if the FDA reviewed all advertising and promotional materials
as well as associated educational materials—for their truthfulness, accuracy, balance, and scientific
validity—before dissemination. Such a change would require a considerable increase in FDA support,
staffing, and funding from what is currently available. Public monies spent on the front end of the problem
could prevent another such tragedy.

The pharmaceutical industry's role and influence in medical education is problematic. From 1996 through
July 2002, Purdue funded more than 20 000 pain-related educational programs through direct sponsorship
or financial grants,19 providing a venue that had enormous influence on physicians’ prescribing throughout
the country. Particularly with controlled drugs, the potential for blurring marketing and education carries a
much higher public health risk than with uncontrolled drugs. At least in the area of controlled drugs, with
their high potential for abuse and diversion, public health would best be served by severing the
pharmaceutical industry's direct role and influence in medical education.

Marketing and promotion by the pharmaceutical industry have considerably amplified the prescription sales
and availability of opioids. A number of factors have contributed to the marked growth of opioid abuse in
the United States, but one factor is certainly the much increased availability of prescription opioids.78 The
public interest and public health would be better served by a redefinition of acceptable and allowable
marketing practices for opioids and other controlled drugs.

Acknowledgments
I thank Michael McNeer, MD, for his thoughtful review of the essay and helpful suggestions.
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 The effects of pharmaceutical firm enticements on physician prescribing patterns. There's no such
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association with addiction.[Ann Intern Med. 2007]

 Review Opioids for chronic nonterminal pain.[South Med J. 2006]

 The NIMH Epidemiologic Catchment Area program. Historical context, major objectives, and
study population characteristics.[Arch Gen Psychiatry. 1984]
 Review Opioids: after thousands of years, still getting to know you.[Clin J Pain. 2007]

 Addiction rare in patients treated with narcotics.[N Engl J Med. 1980]

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 Review Comparative efficacy and safety of long-acting oral opioids for chronic non-cancer pain: a
systematic review.[J Pain Symptom Manage. 2003]
 Review Safety and efficacy of controlled-release oxycodone: a systematic literature
review.[Pharmacotherapy. 2002]

 Recovery of morphine from a controlled-release preparation. A source of opioid abuse.[Cancer.

1990]

 Opioid analgesic involvement in drug abuse deaths in American metropolitan areas.[Am J Public
Health. 2006]
 Trends in abuse of Oxycontin and other opioid analgesics in the United States: 2002-2004.[J Pain.
2005]

 A reassessment of trends in the medical use and abuse of opioid analgesics and implications for
diversion control: 1997-2002.[J Pain Symptom Manage. 2004]

 Increasing deaths from opioid analgesics in the United States.[Pharmacoepidemiol Drug Saf.
2006]

 Review Comparative efficacy and safety of long-acting oral opioids for chronic non-cancer pain: a
systematic review.[J Pain Symptom Manage. 2003]
 Review Safety and efficacy of controlled-release oxycodone: a systematic literature
review.[Pharmacotherapy. 2002]
  Trends in abuse of Oxycontin and other opioid analgesics in the United States: 2002-2004.[J Pain.
2005]

 Review Comparative efficacy and safety of long-acting oral opioids for chronic non-cancer pain: a
systematic review.[J Pain Symptom Manage. 2003]
 Review Safety and efficacy of controlled-release oxycodone: a systematic literature
review.[Pharmacotherapy. 2002]

 Physicians and the pharmaceutical industry: is a gift ever just a gift?[JAMA. 2000]

 Prescriber profiling: time to call it quits.[Ann Intern Med. 2007]

 Review Major increases in opioid analgesic abuse in the United States: concerns and
strategies.[Drug Alcohol Depend. 2006]

Support Center Support Center

  
 
EXHIBIT C
 AJPH RESEARCH

Industry Payments to Physicians for Opioid

Products, 2013–2015
Scott E. Hadland, MD, MPH, MS, Maxwell S. Krieger, BS, and Brandon D. L. Marshall, PhD

Objectives. To identify payments that involved opioid products from the pharma- database implemented under the Physician
ceutical industry to physicians. Payments Sunshine Act.5,7 We used this
Methods. We used the Open Payments program database from the Centers for novel data set to characterize industry pay-
Medicare and Medicaid Services to identify payments involving an opioid to physicians ments to physicians related to opioid
marketing.
between August 2013 and December 2015. We used medians, interquartile ranges, and
ranges as a result of heavily skewed distributions to examine payments according to
opioid product, abuse-deterrent formulation, nature of payment, state, and physician
specialty.
Results. During the study, 375 266 nonresearch opioid-related payments were made METHODS
to 68 177 physicians, totaling $46 158 388. The top 1% of physicians received 82.5% of We extracted all payments between Au-
gust 1, 2013 (when mandated reporting
total payments in dollars. Abuse-deterrent formulations constituted 20.3% of total
began), and December 31, 2015, that listed
payments, and buprenorphine marketed for addiction treatment constituted 9.9%. Most
a US Food and Drug Administration (FDA)–
payments were for speaking fees or honoraria (63.2% of all dollars), whereas food and
approved opioid product. We included
beverage payments were the most frequent (93.9% of all payments). Physicians spe- buprenorphine but examined buprenorphine
cializing in anesthesiology received the most in total annual payments (median = $50; and buprenorphine/naloxone marketed for
interquartile range = $16–$151). addiction treatment separately from the
Conclusions. Approximately 1 in 12 US physicians received a payment involving an buprenorphine transdermal patch marketed
opioid during the 29-month study. These findings should prompt an examination of for pain control. We excluded remifentanil
industry influences on opioid prescribing. (Am J Public Health. 2017;107:1493–1495. doi: (which is marketed exclusively for anesthesia)
10.2105/AJPH.2017.303982) and 2 fentanyl products (1 marketed exclu-
sively for anesthesia, and 1 marketed exclu-
sively for in-hospital pain).

T
We also identified payments involving
he nonmedical use of opioids and when payments are of low monetary value
FDA-recognized abuse-deterrent opioid
overdose mortality have reached un- (e.g., industry-sponsored meals).6 To date,
formulations.8 For comparison with a non-
precedented levels in the United States.1 industry payments to physicians involving
opioid class of pain medications, we quanti-
To respond to concerns about over- opioids have not been studied and de-
fied payments for all actively marketed
prescribing of opioids, the Centers for Disease serve further examination because they nonsteroidal anti-inflammatory drugs
Control and Prevention recently released may impede national efforts to reduce (NSAIDs) in the database. We chose NSAIDs
chronic pain management guidelines that overprescribing. for this comparison because unlike other
call on physicians to consider nonopioid It is currently unclear which opioids are medication classes used for pain that have
pain medications as an alternative to opioids.2 most heavily marketed, to whom, and in additional indications (e.g., medications
Additionally, some physicians and pharma- exchange for which physician activities. The marketed not only for pain but also for de-
ceutical industry representatives have suggested extent to which abuse-deterrent formulations pression or neuralgia), NSAIDs are almost
that abuse-deterrent formulations—newly and nonopioid alternatives are marketed is exclusively used for pain control.
marketed brand-name opioids with pill prop- also poorly understood. For the first time, We limited the current analysis to non-
erties that render misuse more difficult—offer exhaustive data on payments are now avail- research payments to physicians; we excluded
a safer option for prescribers.3,4 able through the Open Payments program research payments, which are made in
Under the recently implemented Physi-
cian Payments Sunshine Act, drug companies
ABOUT THE AUTHORS
are now required to report all transfers of Scott E. Hadland is with Boston Medical Center and Boston University School of Medicine, Boston, MA. Maxwell S. Krieger
value (“payments”) to US physicians.5 and Brandon D. L. Marshall are with Brown University School of Public Health, Providence, RI.
Research suggests that pharmaceutical com- Correspondence should be sent to Scott E. Hadland, MD, MPH, MS, 88 E Newton St, Vose Hall, Room 322, Boston, MA
02118 (e-mail: [email protected]). Reprints can be ordered at http://www.ajph.org by clicking the “Reprints” link.
pany payments promote increased prescribing This article was accepted June 14, 2017.
for marketed brand-name medications, even doi: 10.2105/AJPH.2017.303982

September 2017, Vol 107, No. 9 AJPH Hadland et al. Peer Reviewed Research 1493
AJPH RESEARCH

association with established research pro- TABLE 1—Characteristics of Payments Involving Opioid Products to Physicians: Open
tocols, do not explicitly target prescribing Payments Program Database, United States, August 1, 2013–December 31, 2015
behaviors, and may be provided to physicians
not actively practicing medicine. We sum- Nature of Payment Total Payment Amount, $ (%) Median Payment, $ (IQR) No. of Payments (%)
marized payments in terms of total dollars
Speaking fees or honoraria 29 190 854 (63.2) 2 010 (1 000–3 750) 9 161 (2.4)
and number of payments made and identified
Food and beverages 7 872 581 (17.1) 14 (11–18) 352 298 (93.9)
changes from 2014 to 2015 (the 2 years for
which all 12 months of data were available). Consulting fees 5 886 461 (12.8) 1 000 (500–2 500) 2 145 (0.6)
We used medians, interquartile ranges Travel and lodging 2 904 940 (6.3) 537 (100–1 131) 4 048 (1.1)
(IQRs), and ranges as a result of heavily Education 222 869 (0.5) 14 (5–25) 7 422 (2.0)
skewed distributions to examine payments
Othera 80 683 (0.2) 100 (14–500) 192 (0.1)
according to opioid product, abuse-deterrent
formulation, nature of payment (i.e., physi- Note. IQR = interquartile ranges.
a
cian activity leading to the payment), state, Includes gifts, entertainment, and space rental or facility fees.
and physician specialty. We also assessed
payments to physicians receiving the top 1% with physicians receiving a median of 1 pay- are. Additionally, despite Centers for Disease
of payments for opioids. We used Stata ver- ment annually (IQR = 1–2; maximum = 157). Control and Prevention recommendations to
sion 13.1 (StataCorp LP, College Station, Payments were positively skewed, with the consider use of nonopioid medications for
TX) for analyses. top 1% of physicians (n = 681) receiving pain, NSAIDs, a prominent family of non-
$2639 or more annually (Table A, available as opioid pain medications, were not as heavily
a supplement to the online version of this marketed as opioids were.2
article at http://www.ajph.org). These phy- Fentanyl was the most common opioid
RESULTS sicians collectively received $38 073 796 involved in payments to physicians. National
Over the study period, 375 266 non- (82.5% of total payments) during the study data implicate fentanyl in a rapidly increasing
research payments involving a marketed period. number of overdose deaths, although most
opioid were made to 68 177 physicians, to- Physicians specializing in anesthesiology are caused by illicitly manufactured fen-
taling $46 158 388. Total payments increased received the most in total annual payments tanyl.10 Further studies should clarify the
from $18 958 125 in 2014 to $20 996 858 in (median = $50; IQR = $16–$151; n = 4339), extent to which industry payments contribute
2015, an increase of 10.7%. The number followed by physical medicine and rehabili- to prescribing patterns and overdose rates
of payments increased from 145 715 in 2014 tation (median = $48; IQR = $14–$145; across geographic regions, particularly given
to 184 237 in 2015, an increase of 26.4%. n = 3502) and pain medicine (median = $43; the heterogeneity we observed in payments
The 5 opioid products constituting the IQR = $12–$125; n = 3090). Physicians among states. Although payment amounts
greatest proportion of payments were fentanyl specializing in family medicine received in dollar terms were greatest to physicians
($21 240 794; 46.0% of total dollars), hydro- the largest total number of payments specializing in anesthesiology, physical
codone ($7 123 421; 15.4%), buprenorphine (n = 20 592). medicine and rehabilitation, and pain
transdermal patch ($5 141 808; 11.1%), oxy- medicine—specialists with expertise in pain
codone ($4 487 978; 9.7%), and tapentadol management—family medicine physicians
($4 296 130; 9.3%). Overall, payments for received the largest number of payments,
FDA-approved abuse-deterrent formulations DISCUSSION indicating extensive marketing of opioid
totaled $9 352 959 (20.3%), and payments for According to the Association of American products to primary care physicians. Because
buprenorphine or buprenorphine/naloxone Medical Colleges, there were 829 962 active there were 108 917 active family physicians
marketed for addiction treatment totaled physicians in the United States at the be- in the United States in 2013,9 our data
$4 561 729 (9.9%). By comparison, payments ginning of the study period in 20139; thus, our highlight that nearly 1 in 5 received an
for NSAIDs amounted to $13 758 385 (not results suggest that 1 in 12 physicians received opioid-related payment.
included in previous totals). an industry payment involving an opioid A limitation of this study was the absence
Speaking fees or honoraria constituted the during the 29-month study period. Although of further details about industry-physician
largest proportion of payments in dollars, half of all the annual payments were $15 or interactions; some payments may have sup-
whereas payments involving food and bev- less, even small payments (including meals) ported education on appropriate prescribing
erage were the most common (Table 1). are associated with increased prescribing of behaviors.11 One tenth of the payments in-
Payments varied widely according to marketed products.6 FDA-approved abuse- volved buprenorphine marketed for addic-
US state (Figure A, available as a supple- deterrent formulations, which have proper- tion treatment, which may have resulted
ment to the online version of this article ties expected to render misuse less likely, in improved education on addiction care.
at http://www.ajph.org). The median constituted only one fifth of the total pay- Risk Evaluation and Mitigation Strategies
paid per physician annually was $15 ments, suggesting that such medications may programs imposed by the FDA require
(IQR = $7–$42; maximum = $1 539 471), not be as heavily marketed as other opioids education on extended-release/long-acting

1494 Research Peer Reviewed Hadland et al. AJPH September 2017, Vol 107, No. 9
 AJPH RESEARCH

opioids and on transmucosal fentanyl prod- 4. Alexander L, Mannion RO, Weingarten B, Fanelli RJ,
Stiles GL. Development and impact of prescription opioid
ucts, and some industry payments to physi- abuse deterrent formulation technologies. Drug Alcohol
cians may have been related to this regulation. Depend. 2014;138:1–6.
Another limitation was that some abuse- 5. Agrawal S, Brown D. The Physician Payments Sun-
deterrent formulations were approved part- shine Act — two years of the open payments program.
N Engl J Med. 2016;374(10):906–909.
way through the study period; in future years,
such medications might be associated with 6. DeJong C, Aguilar T, Tseng C-W, Lin GA, Boscardin
WJ, Dudley RA. Pharmaceutical industry-sponsored
a greater portion of industry payments. meals and physician prescribing patterns for Medicare
beneficiaries. JAMA Intern Med. 2016;176(8):1114–1122.
7. Centers for Medicare & Medicaid Services. Open
Payments. 2016. Available at: https://www.cms.gov/
openpayments. Accessed February 12, 2017.
PUBLIC HEALTH IMPLICATIONS 8. US Food and Drug Administration. FDA facts:
To our knowledge, this was the first abuse-deterrent opioid medications. April 2017. Available
large-scale examination of industry payments at: http://www.fda.gov/NewsEvents/Newsroom/
FactSheets/ucm514939.htm. Accessed July 3, 2017.
involving opioids. Financial transfers were
substantial and widespread and may be in- 9. Association of American Medical Colleges. 2014
Physician Specialty Data Book. November 2014. Available
creasing in number and value. Although at: https://members.aamc.org/eweb/upload/
opioid prescribing declined nationally during PhysicianSpecialtyDatabook2014.pdf. Accessed February
the study period,12 these results should 12, 2017.

prompt an examination of industry influences 10. Gladden RM, Martinez P, Seth P. Fentanyl law
enforcement submissions and increases in synthetic opi-
on prescribing amid an ongoing opioid crisis. oid–involved overdose deaths — 27 states, 2013–2014.
Further research should examine whether MMWR Morb Mortal Wkly Rep. 2016;65(33):837–843.
payments are related to opioid misuse and 11. Sismondo S. Key opinion leaders and the corruption
overdose, and policymakers might consider of medical knowledge: what the Sunshine Act will and
won’t cast light on. J Law Med Ethics. 2013;41(3):635–643.
whether caps should be imposed on certain
12. Goodnough A, Tavernise S. Opioid prescriptions
payments. drop for first time in two decades. New York Times. May
20, 2016:A1.
CONTRIBUTORS
S. E. Hadland and B. D. L. Marshall designed the study
and wrote the protocol. S. E. Hadland conducted the
literature review and wrote the first draft of the article.
M. S. Krieger undertook data management and statistical
analyses with additional input from S. E. Hadland and
B. D. L. Marshall. All authors contributed to and approved
the final article.

ACKNOWLEDGMENTS
S. E. Hadland is supported by the National Institutes
of Health/National Institute on Drug Abuse (Loan
Repayment Program Award L40 DA042434). B. D. L.
Marshall is supported by the Henry Merrit Wriston
Fellowship at Brown University.
We would like to thank Jesse Yedinak, MPA, for her
research and administrative assistance and David Fiellin,
MD, and Jason Vassy, MD, MPH, SM, for their review of
the article.

HUMAN PARTICIPANT PROTECTION

The study was considered exempt by the Brown Uni-
versity institutional review board.

REFERENCES
1. Rudd RA, Aleshire N, Zibbell JE, Gladden RM.
Increases in drug and opioid overdose deaths - United
States, 2000-2014. MMWR Morb Mortal Wkly Rep. 2016;
64(50-51):1378–1382.
2. Dowell D, Haegerich TM, Chou R. CDC guideline
for prescribing opioids for chronic pain–United States,
2016. JAMA. 2016;315(15):1624–1645.
3. Webster LR, Markman J, Cone EJ, Niebler G. Current
and future development of extended-release, abuse-
deterrent opioid formulations in the United States.
Postgrad Med. 2017;129(1):102–110.

September 2017, Vol 107, No. 9 AJPH Hadland et al. Peer Reviewed Research 1495
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EXHIBIT E 
 A Reporter’s Guide:
Covering Pain and Its Management
A Reporter’s Guide: Covering Pain and Its Management 1
Pain is a complex perception that differs
enormously from one person to another, even those
with seemingly identical injuries or illnesses.
 Introduction
Everyone has experienced pain—whether it’s a pounding headache at the end of a
long day, a throbbing toothache warning of a cavity or infection, an open wound
or sprained ankle from a fall, or a stinging burn from touching a hot pan.
There are hundreds of pain syndromes, and pain is often a chief symptom of most
chronic conditions, including cancer, diabetes, arthritis, fibromyalgia and a host of
neurological disorders. For millions of Americans, pain persists, interfering with
everyday activities and enjoyment of life. People living with chronic pain will often
avoid certain movements or activities, fearful they will cause more injury or to
avoid the anxiety of anticipated pain.

Pain is complex and frequently misunderstood by the public. The issue of pain is riddled
with myths and misperceptions, which makes the task of informing and educating people
about pain and its management that much more challenging.

SOME COMMON MISCONCEPTIONS ABOUT PAIN

n Pain is “all in your head.” Although this physician or nurse might “guess” about
is partially true because we need our someone’s actual pain. The person with
brains for the perception of pain, that pain is the authority on the existence and
does not mean pain is imaginary when severity of his/her pain. The self-report is
the source of pain is not well understood. most reliable indicator.
n
Pain is all too real to the person who lives Seeking medical care for pain is a sign
with it day in and out. of weakness. Pain carries a stigma, and
n Pain is just something one has to live many people hesitate talking about their
with—an inevitable part of a disease or pain and how it affects their daily life;
condition. The fact is most pain can be they also don't want to be considered a
relieved with proper pain management. “bad” patient.
n Pain is a natural part of growing older. n Use of strong pain medication leads to
While pain is more common as we age addiction. Many people living with pain
because conditions that cause pain (e.g., and even some healthcare providers falsely
arthritis, degenerative joint diseases, believe opioids (strong pain medicines) are
cancer, shingles, osteoporosis) are more universally addictive. Studies have shown
frequent in older adults, it should not be that the risk of addiction is small when
something people have to struggle with. these medicines are properly prescribed
n The best judge of pain is the physician and taken as directed. As with any
or nurse. Studies have shown that there medication, there are risks, but these risks
is little correlation between what a can be managed.

A Reporter’s Guide: Covering Pain and Its Management 1

Key Reporting Challenges

• Stigma of pain management, especially among legal and

A limited and informal government regulatory bodies
survey of reporters, • Hesitancy on the part of patients and providers to discuss
opioids for legitimate chronic pain management given
editors and producers misperceptions about opioids and addiction
revealed the following • Ability to find unbiased, credible information about pain
challenges when
• Limited number of randomized controlled trials
researching and
• Finding pain patients who live with the type of pain and/or
covering the pain/pain use the pain management approach being reported in the
management story: news story
• Accurately characterizing the pain experience given that every
person experiences pain differently, even if they have a similar
injury or illness

THE UBIQUITOUS NATURE OF PAIN

Consider the following…

n Most Americans (80%) will suffer from back pain at some point in their lives.
n As we age, arthritis hinders the normally smooth sliding motion of our joints and connective
tissues, resulting in stiffness and discomfort. Arthritis is the leading cause of disability in people
over the age of 55.
n Pain associated with pediatric immunizations is a significant source of anxiety for children
receiving the immunizations, and evidence suggests that the way children and parents cope
can set the stage for future pain responses.
n Damage to or dysfunction of the central nervous system, due to stroke, multiple sclerosis,
epilepsy, brain or spinal cord injuries or Parkinson's disease, also stimulates pain pathways.
n An estimated 30 to 50% of patients undergoing active treatment for cancer and 70% of those
with advanced stages of the disease experience significant levels of pain and may be reluctant
to discuss their pain with their doctors.

Sources: The American Academy of Physical Medicine and Rehabilitation, Arthritis Foundation, Mayday Fund, National Institute of
Neurological Disorders and Stroke, National Cancer Institute.

2 American Pain Foundation

 Purpose of This Guide

The American Pain Foundation (APF) has developed this Guide as a primer on
pain and pain management to help meet the informational needs of busy reporters,
editors and producers covering the pain story. We know it's a complex topic, and
hope you will find this to be a useful resource.

INSIDE YOU WILL FIND:

Page
n A basic overview of the burden of pain in America, consequences
of unmanaged pain, pain assessment tools and treatment options....................................4
n Pain Stats & Facts ....................................................................................................................10
n Special Topic Briefs covering
– Special Considerations: Pain in Specific Populations......................................................13
– Pain Management and Disparities ..................................................................................23
– Chronic Pain and Opioid Therapy ..................................................................................27
At a Glance: Differentiating addiction, physical dependence and tolerance
– Integrative Medicine: Non-Drug Treatment Options for Pain Management ..................35
n Pain A to Z: Common Pain Terms and Syndromes............................................................40
n Online Pain Resource .............................................................................................................43

Be sure to visit the Newsroom section of the American Pain Foundation’s web site at
www.painfoundation.org to download additional copies and to check for posted updates and new
Topic Briefs as they are added. Here you will also find recent news releases, press statements and
background information on a wide variety of issues related to pain care.

ABOUT THE AMERICAN PAIN FOUNDATION providers and advocates, who are working hard to call
APF’s mission is to improve the quality of life for attention to the urgent need for positive changes in
people with pain by: pain policy, practice and research investment.
• Raising public awareness;
EXPERTS AVAILABLE FOR INTERVIEW
• Providing practical information, education and
support; APF can connect reporters with a wide array of leading
pain experts, as well as people living with pain
• Advocating to remove barriers and increase access
and their caregivers. Whether you are working on
to effective pain management; and,
a national or local story, we can help coordinate
• Promoting research. interviews about pain-specific conditions and
Since its founding in 1997, the American Pain other important issues related to pain (e.g., depression,
Foundation (APF) has been at the forefront of coping skills, financial matters, disparities, treatment
advocating for people living with a wide variety of options).
pain conditions and their caregivers.
If you are interested in interviewing someone at
Our grassroots effort, Power Over Pain Action Network, APF or need additional resources, please contact
is now active in nearly 40 states and is comprised Tina Regester, APF’s communications manager, at
of people living with pain, caregivers, healthcare (443) 690-4707 or [email protected].

A Reporter’s Guide: Covering Pain and Its Management 3

A Primer on Pain and Its Management

BURDEN OF PAIN IN
AMERICA: AN EVOLVING
PUBLIC HEALTH CRISIS
Pain is a serious and costly
public health issue. It affects PAIN IS WOEFULLY UNDERTREATED FOR A
more Americans than VARIETY OF REASONS, INCLUDING:
diabetes, heart disease and
n Misconceptions about opioid addiction
cancer combined, and is a
n Lack of access to care
leading cause of disability in
n Cultural norms and the stigma associated with admitting
the United States. Even though pain
pain is one of the most n Limited or no professional training in pain management,
common reasons patients which leaves healthcare providers ill-equipped to effectively
consult a healthcare provider, respond to patients’ reports of pain
it is often inadequately n Concerns among physicians about prescribing pain
medications for chronic pain, and fears of scrutiny by
assessed and treated, resulting
regulators or law enforcement
in needless suffering and poor
n Inadequate funding for pain research (less than 2% of
patient outcomes. NIH research budget was dedicated to pain studies)

Untreated or poorly managed pain can compromise every aspect of

life, including a person’s physical and mental health, social and
intimate relations, ability to sleep and perform everyday tasks, work
productivity and financial well being.

Chronic pain is not only emotionally and physically debilitating for

patients, it also places a tremendous burden on families and
caregivers, and contributes to excessive healthcare costs. The
economic toll of chronic pain exceeds $100 billion each year in the
United States alone. As the 75 million Baby Boomers move toward
retirement, the epidemic of untreated or undertreated pain is
expected to continue.

More than one-quarter of Americans (26%) age 20 years and over—or, an

estimated 76.5 million people—report that they have had a problem with
pain. This number does not account for acute pain.
Source: National Center for Health Statistics,2006.

4 American Pain Foundation

PAIN BASICS
The International Association for the Study of Pain defines pain as: An unpleasant
sensory and emotional experience associated with actual or potential tissue
damage or described in terms of such damage.

At its best, pain is the body’s natural alarm system, alerting us to

COMMON PAIN CONDITIONS injury (or further injury if already injured). It prompts us to stop a
harmful behavior or seek medical attention. For example, lifting
• Headaches or migraine
too much weight might result in a piercing pain in a person’s
• Back pain and sciatica back. Within moments of touching a hot surface, the fiery
• Neck and shoulder pain sensation of a burn warns us to quickly pull away. Worsening
• Joint pain due to arthritis, abdominal pain may be a sign of appendicitis or other serious
bursitis, fibromyalgia or infection. Pain also triggers inflammation, which directs healing
degenerative joint disease cells to the area of injury. The experience of pain also beckons
• Muscle pain from overuse the injured person to rest, promoting healing.
or strain, injury or
fibromyalgia At its worst, unrelenting pain robs people of their livelihood and
• Post-surgical pain well being. When pain persists, it is often a sign that
the body’s alert system has broken down. In other words, pain
signals remain active. Over time, this heightened response may:
For definitions of these
and other pain conditions, • Harm the nerves, blood vessels and organs
as well as common pain • Suppress immune function
terms, please refer to the • Result in excessive inflammation
Pain A to Z listing at the • Delay healing
back of this resource.
Since the brain remembers pain, pain may be imprinted into the
nerve tissue and continue to send pain sensations even in the
absence of painful stimuli.

Chronic Pain-Brain Connection

New research is unraveling how chronic activation of the
biological pathways transmitting pain is associated with structural
and chemical changes in the brain. A recent study suggests that
constant pain signals can result in mental rewiring that affects the
frontal cortex, the area of the brain mainly associated with
emotion and attention. According to researchers, this provides
the first objective proof of brain disturbances in patients with
chronic pain that is unrelated to the sensation of physical pain.

A Reporter’s Guide: Covering Pain and Its Management 5

ACUTE VS. CHRONIC PAIN
There are two main types of pain: acute and chronic.

AC U T E PA I N C H R O N I C PA I N

Onset Usually sudden Sudden or gradual development

Cause Typically linked to an event, Contributing factors are less certain
such as an injury or disease
Duration Temporary (up to 3 months) Persistent (beyond usual healing time
or longer than 3 months)
Pain Identification Painful areas are generally well Painful areas are less easily
identified differentiated
Pattern Self-limiting or readily corrected Continuous or intermittent; intensity
may vary or remain constant
Course Pain usually lessens over time Pain usually increases over time
Response Stress response may be present Stress response often absent
(increased heart and/or breathing rate,
increase in blood pressure)
Prognosis Total relief typically possible Total relief often impossible

Adapted from: McCance K, Huether SE, eds. Pathophysiology: the biologic basis for disease in adults and children. 5th ed. New York, NY: Elsevier,
2006:447-489.

Acute Pain occurs suddenly due to illness, inflammation, injury or surgery. It has a short
duration that subsides when the injured tissue heals. The cause of the pain can usually be
diagnosed and treated.

Chronic Pain is pain that lasts long enough (after normal healing or for at least three
months), or is intense enough, to affect a person’s normal activities and well-being.
Failure to treat acute pain promptly and appropriately at the time of injury, during initial
medical and surgical care or at the time of transition to community-based care,
contributes to the development of chronic pain syndromes.

With chronic pain, pain signals may remain active in the nervous system for weeks,
months or even years. Unlike acute pain, chronic pain has no value or benefit; it is a
disease in its own right. It can also be especially challenging to treat.

6 American Pain Foundation

 PAIN ASSESSMENT
Timely access to quality pain management is the best way to minimize the
suffering and disability often associated with undertreated pain and to avoid
additional problems down the road. Science is revealing the role of unrelieved
acute pain in the development of chronic, persistent pain.

Most hospitals, nursing homes and other healthcare facilities are now required to
assess and treat pain. To correctly diagnose pain, healthcare professional will:
• Perform a thorough physical exam
• Complete a pain assessment
• Ask detailed questions about the patient’s medical history and lifestyle
• Order blood work, X-rays, electrical tests to detect nerve damage, or
other diagnostic and laboratory tests

Pain is a subjective experience, and it is critical for healthcare professionals to

have a complete picture of the patient’s pain history. He/she may ask about
seven characteristics of pain to help LOCATE the pain and make the correct
diagnosis.

L the exact Location of the pain and whether it

travels to other body parts
O Other associated symptoms such as nausea, numbness, or weakness
C The Character of the pain, whether it’s throbbing, sharp, dull or burning
A Aggravating or Alleviating factors. What makes the pain better or worse?
T the Timing of the pain, how long it lasts, is it constant or intermittent?
E the Environment where the pain occurs, for example, while working or
at home

The type of pain someone is experiencing is often a clue to its cause; for
example, chronic pain that is burning or tingling is often the result of nerve
disease (neuropathy).

EFFECTS OF UNRELIEVED CHRONIC PAIN ON PHYSICAL AND MENTAL HEALTH

If untreated, pain can have serious physiological, psychological and social consequences. It can:

n Limit the ability to work, sleep, exercise or n Aggravate other health problems
perform everyday tasks (for example, dressing, n Lead to depression and/or anxiety, which often
going to the grocery store)
worsen pain sensations
n Reduce mobility
n Make it difficult to concentrate or reason
n Impair strength
n Place added strain on relationships and interfere
n Diminish appetite with intimacy
n
n
Make it difficult to recover from an injury or fight Result in a loss of self-esteem and independence
infection by weakening the immune system

A Reporter’s Guide: Covering Pain and Its Management 7

Pain scales are additional tools available to help patients describe the intensity of their pain. These assessment
tools help healthcare professionals diagnose or measure a patient’s level of pain. These include numeric, verbal or
visual scales.

With numerical scales, patients use numbers from 0-10 (0 being no pain and 10 being the worst pain ever) to
rate the intensity of the pain.

Verbal scales contain commonly used words such as “mild,” “moderate” and “severe” to help patient’s describe
the severity of the pain.

Visual scales use aids like pictures of facial expressions, colors or gaming objects, such as poker chips, to help
explain the severity of pain. One type, the Wong Baker Faces Pain Rating Scale, shows six different facial
expressions from happy (no hurt) to agony (hurts the worst) to help show healthcare professionals how much
pain a patient feels. Body diagrams may also be used to help pinpoint where the pain occurs.

From Hockenberry MJ, Wilson D, Winkelstein ML: Wong’s Essentials of

Pediatric Nursing, ed. 7, St. Louis, 2005, p. 1259. Used with permission.
Copyright, Mosby.

Multidimensional pain assessment tools, such as the McGill Pain Questionnaire (MPQ) and the Brief Pain
Inventory (BPI), have been developed to quantify different aspects of pain, including location and quality of pain
and its effect on mood and function. However, these take longer to administer than the simpler scales and some
patients who are cognitively impaired or poorly educated may find them difficult to complete. They are generally
used in pain research, but can be adapted for clinical use if appropriate and valuable.

Our processing of pain is complex. A basic explanation is that the pain signals of acute pain are initiated when receptors on the
skin, within an organ, tissue or nerve are triggered by injury or disease, known or unknown. A series of events follow: an
electrical impulse, or pain message, is generated that is then carried on nerve fibers to the spinal cord. The spinal cord transmits
the pain signal to various levels of the brain for interpretation and response. At any time during the transport of pain messaging,
these noxious signals can be blocked, enhanced or modified. Signaling associated with chronic pain is much more complicated
than acute pain as science is beginning to show.

8 American Pain Foundation

 TREATING PAIN
Successful pain management aims to:
1) lessen the pain
2) improve functioning and
3) enhance quality of life
Pain treatment needs to be individualized and, in most cases, requires a team of
providers, as well as social support from family and friends. Most often, an
integrative approach is needed to provide pain relief, which includes a
combination of treatment options; this also encourages patients to actively
participate in self-care. Treatment options may include:
• Medication (anti-inflammatory medicines, opioids or other classes of drugs)
• Psychosocial interventions (cognitive-behavioral counseling, guided imagery)
• Rehabilitative approaches (exercise, application of heat/cold, myofascial release,
occupational therapy, if needed)
• Complementary alternative medicine (massage, acupuncture, hypnosis)
• Injection or infusion therapies
• Implantable devices and surgical procedures
Research shows that pain can affect patients’ emotions and behavior and interfere
with the ability to concentrate, manage everyday tasks and cope with stress.
Likewise, stress and emotional pressures can make pain worse, provoking “flare
ups” and contributing to alterations in the immune system response. These
relationships are not always easily recognized or readily fixed by medical
procedures or medications alone.
New treatments under investigation are aimed at the physical, psychological and
environmental components of chronic pain. Research is also examining the role
of genetic predisposition and the immune system in mitigating pain signals.
For a detailed description of the different treatment modalities for managing pain,
please refer to the America Pain Foundation’s Treatment Options: A Guide for
People Living with Pain.

MEDICATIONS & PAIN MANAGEMENT

Medications play an important role in the treatment of pain. There are three major classes of medications for
pain control:
Non-opioids: non-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen
Opioids: morphine, oxycodone, methadone, codeine and fentanyl are examples
Adjuvant analgesics: a loose term referring to the many medications originally used to treat conditions
other than pain, but now also used to help relieve specific pain problems; examples include some
antidepressants and anticonvulsants. Some of these drugs have been shown to work well for specific types
of pain.
Drugs that have no direct pain-relieving properties may also be prescribed as part of a pain management
plan. These include medications to treat insomnia, anxiety, depression and muscle spasms, and can help a
great deal in the overall management of pain in some persons.

A Reporter’s Guide: Covering Pain and Its Management 9

Pain Facts & Stats
PREVALENCE OF PAIN
Pain is a serious and costly public health problem.

n A hallmark of many chronic conditions, pain affects more Americans than diabetes, heart disease and cancer
combined.

ESTIMATED INCIDENCE*

80
26%
70
60
50
40
*Sources:
30 Pain – 76.2 million people, National Centers for Health Statistics
Diabetes – 20.8 million people (diagnosed and estimated
20 7% 6%
undiagnosed), American Diabetes Association
Coronary Heart Disease, including heart attack and chest pain, and
10 1.4% Stroke – 18.7 million people, American Heart Association
Cancer – 1.4 million people, American Cancer Society
0

n More than one-quarter of Americans (26%) age 20 years and over—or, an estimated 76.5 million Americans—
reported that they have had a problem with pain of any sort that persisted for more than 24 hours in
duration. This number does not account for acute pain.1
n About one-third of people who report pain indicate that their pain is “disabling,” defined as both severe
and having a high impact on functions of daily life.2
n More women (27.1%) than men (24.4%) report that they are in pain.1
n Non-Hispanic white adults reported pain more often than adults of other races and ethnicities
(27.8% vs. 22.1% Black only or 15.3% Mexican).1
n Adults living in families with income less than twice the poverty level reported pain more often than higher
income adult.1
n When asked about four common types of
pain, respondents of a National Institute of FOUR COMMON TYPES OF PAIN
Health Statistics survey indicated that low
back pain was the most common (27%), Low Back Pain 27%
followed by severe headache or migraine
pain (15%), neck pain (15%) and facial ache Migraine Pain 15%
or pain (4%).1
Neck Pain 15%

Facial Pain 4%

0 10 20 30 40 50

10 American Pain Foundation

DURATION OF PAIN DURATION OF PAIN
n Adults 20 years of age and over who report pain said that it lasted:
• Less than one month – 32%
• One to three months – 12% <1 month
42% 32%
• Three months to one year – 14%
> 1 year
• Longer than one year – 42%
12%
14% 1-3 months

3 months – 1 year
ECONOMIC AND WORKPLACE BURDEN OF PAIN

n The annual cost of chronic pain in the United States, including healthcare
expenses, lost income, and lost productivity, is estimated to be $100 MUCH WORK REMAINS
billion.3 However, more recent studies have indicated that costs associated • Currently, less than 2%
with low back pain alone are an estimated $85.9 billion.4 The total cost of the NIH research
of arthritis—the nation’s leading cause of disability—is estimated at $128 budget is dedicated to
billion.5
pain.
n Undertreated pain drives up the cost of healthcare because it extends
• More than half of all
lengths of stay in hospitals, increases emergency room visits and results in
unplanned clinic visits. hospitalized patients
experienced pain in the
n Pain is the second leading cause of medically related work absenteeism, last days of their lives
resulting in more than 50 million lost workdays each year.6 and although therapies
n Lost productive time due to headache, arthritis, back pain and other are present to alleviate
musculoskeletal conditions is estimated to cost $61.2 billion per year.7 most pain for those
• Headache was the most common (5.4%) pain condition resulting in dying of cancer, research
lost productive time. It was followed by back pain (3.2%), arthritis shows that 50-75% of
pain (2.0%), and other musculoskeletal pain (2.0%). patients die in moderate
• Most (76%) of the pain-related lost productive time was in the form of to severe pain.8
reduced performance occurring while the employees were at work,
rather than absenteeism.
• Workers who experienced lost productive time from a pain condition
lost an average of 4.6 hours per week.

For more statistics and research findings, see our Topic Briefs on: Be sure to visit the
n Special Considerations: Pain in Specific Populations American Pain Foundation at
n Disparities and Pain Management www.painfoundation.org for
n Integrative Medicine: Non-Drug Treatment Options for posted updates and additional
Pain Management Topic Briefs.
n Chronic Pain and Opioid Treatment

A Reporter’s Guide: Covering Pain and Its Management 11

REFERENCES
1. National Center for Health Statistics. Health, United States, 2006, Special Feature on Pain With Chartbook on Trends in the
Health of Americans. Hyattsville, MD. Available at http://www.cdc.gov/nchs/data/hus/hus06.pdf.
2. Portenoy, R, Ugarte C, Fuller I, Haas G. ”Population-based Survey of Pain in the United States: Differences Among White,
African American, and Hispanic Subjects” Journal of Pain, Vol 5, Issue 6, 2004; pp 317-318.
3. National Institutes of Health. NIH Guide: New Directions in Pain Research I. September 4, 1998. Available from
http://grants.nih.gov/grants/guide/pa-files/PA-98-102.html.
4. Brook I. Martin, MPH; Richard A. Deyo, MD, MPH; Sohail K. Mirza, MD, MPH; Judith A. Turner, PhD; Bryan A. Comstock, MS;
William Hollingworth, PhD; Sean D. Sullivan, PhD. “Expenditures and Health Status Among Adults With Back and Neck
Problems.” JAMA. 2008;299(6):656-664.
5. Centers for Disease Control and Prevention. “Targeting Arthritis: Improving Quality of Life for More than 46 Million Americans.”
At a Glance 2008. Retrieved March 6, 2008 from http://www.cdc.gov/nccdphp/publications/aag/arthritis.htm.
6. American Pain Society. “Pain Assessment and Treatment in the Managed Care Environment.” January 11, 2000. Available at
http://www.ampainsoc.org/advocacy/assess_treat_mce.htm.
7. Stewart WF, Ricci JA, Chee E, Morganstein D, Lipton R. Lost Productive Time and Cost Due to Common Pain Conditions in the
US Workforce. JAMA. 2003;290:2443-2454.
8. Weiss SC, Emanuel LL, Fairclough DL, Emanuel EJ. Understanding the experience of pain in terminally ill patients. Lancet. 2001;
357:1311-1315.

“The moral test of a society is how that society treats those

who are in the dawn of life...the children; those who are in
the twilight of life...the elderly; and those who are in the
shadows of life...the sick, the needy and the handicapped.”
—Hubert Humphrey

12 American Pain Foundation

 Topic Brief
SPECIAL CONSIDERATIONS: PAIN IN SPECIFIC POPULATIONS
Although pain is a significant problem among all Americans, certain populations are more susceptible to and at greater risk for
undertreatment, including children, minorities and those with advanced, life-limiting medical illness. Studies conducted in
emergency departments suggest that women receive less attention in response to reports of severe pain than men. As well,
active duty military and veterans tend to experience pain differently and present greater challenges to achieving optimal pain
relief.
In order to provide the most effective pain care possible and minimize pain-related morbidity, characteristics of vulnerable
populations must be taken into consideration when performing pain assessment and implementing treatment plans.
Healthcare professionals must also become aware of their own biases and understand that, regardless of demographic or
social position, every individual with pain requires evaluation and treatment tailored to his or her specific clinical
circumstances.

Children and Pain

Every child will experience pain at • Recent evidence reveals reduced Many things affect the way
one time or another, whether it’s pain sensitivity is a common a child experiences, communicates
from everyday bumps and bruises, feature of children with autism and responds to pain, including:
or more chronic conditions such and Asperger’s syndrome.2 • Their age
as headaches, gastrointestinal • Musculoskeletal pain can result • Their beliefs and understanding
problems or diabetes. In fact, from “growing pains,” a normal of what is causing the pain
research shows that as many as
occurrence in about 25 to 40% • Their ability to cope
40% of children and adolescents
of children.5 • Their activity and anxiety levels
complain of pain that occurs at
least once weekly, and chronic COMMON CAUSES OF PAIN • Previous experiences with pain
pain affects at least 15 to 20% of IN CHILDREN and how they learned to
children.1 And pediatric pain stems respond
from a wide range of chronic • Scrapes and bruises
• Needlestick pain from immunizations • Support from parents and
conditions:
(most children receive up to 24 siblings
• Each year, 1.5 million children
immunizations by their 2nd birthday) • Preliminary data suggest that
have surgery, and many receive
• Sports injuries (e.g., sprains, a mother’s anxiety may be
inadequate pain relief. In 20%
transmitted more strongly to
of cases, the pain becomes concussion, fractures)
her daughters than her sons,
chronic.2 • Chronic illnesses (e.g., sickle cell resulting in increased anxiety
• Of children aged 5 to 17 years, disease, Type I diabetes) and pain in girls, but not
20% suffer headaches.2 • Headaches boys.6
• More than one-third of children • Abdominal pain (e.g., ulcerative If pain is not addressed and
complain of abdominal pain colitis) treated early on, it can greatly
lasting two weeks or longer.3 impact a child’s quality of life by
According to the American interfering with mood, sleep,
• Juvenille arthritis, which causes Medical Association, children and
joint inflammation and aches, appetite, school attendance,
infants are at increased risk of academic performance, and
affects nearly 250,000 people inadequate pain management, participation in sports and other
under the age of 16 years.4 with age-related factors playing a extracurricular activities. Further, if
• By 2010, 1 in 1,000 U.S. children major role. Physical and unrelieved, childhood pain can
will be a survivor of childhood psychological changes that occur enhance a child’s7 vulnerability to
cancer and may have to deal during childhood development pain later in life. It is essential that
with late and long-term effects can make understanding and healthcare providers begin to
of treatment (e.g., chronic managing pain in children approach pediatric pain so that
fatigue and pain syndromes, significantly more complicated appropriate strategies can be
nerve damage).2 than treating pain in adults. devised to target and reduce

A Reporter’s Guide: Covering Pain and Its Management 13

 children’s distress and pain-related MYTHS AND TRUTHS ABOUT PAIN IN CHILDREN
disability. MYTH: Children who are playing or sleeping must not be in pain.
Unaddressed pain can also result TRUTH: Children cope with pain by distracting themselves, often
in significant financial stress for through play. Sleep may also be a coping mechanism,
families who not only have to and/or because they are exhausted.
cover healthcare expenses, but
who may also have to 8miss work MYTH: Young infants do not feel pain because their nervous systems
to care for a sick child. are immature and unable to perceive and experience pain
the way adults do.
Inadequate prevention and relief
TRUTH: Decades ago it was believed that a newborn couldn’t feel
of pediatric pain are still
pain, and surgery was routinely performed on infants
widespread. Many obstacles exist
without anesthetic. Today, we know that the central nervous
to providing appropriate pain care
10 system of a 26-week-old fetus has the capability of
to children and adolescents:
experiencing pain. There is strong evidence that children
• Beliefs and attitudes about the experience increasing anxiety and perception of pain with
8
experience of pediatric pain. multiple procedures or painful stimuli.
• General lack of understanding
MYTH: Children can easily become addicted to pain medications.
about the best course of action
for treating children in pain. TRUTH: Less than9 1% of children treated with opioids become
addicted.
• Belief that pain should be
treated less aggressively in MYTH: Children cannot effectively communicate their pain; it is
children than adults. difficult to know when they have pain.
• Pediatric pain management TRUTH: Children don’t communicate, respond to, or feel pain the
research has not been effectively same way adults do, so it’s difficult for health professionals
translated into routine clinical and parents to understand what they are experiencing. But,
practice. it is very real and not something they easily forget about.
• Pain in children with disabilities There are many tools available to assess pain in children.
or other special health care Adults need to recognize how children of different ages
needs may be more difficult to express pain in both behaviors and words.
assess. MYTH: Children will tell adults when they are having pain.
TRUTH:: Children may not have the words to express pain (e.g.,
hurt, “ouch”) or know to point to where it hurts. They may
also be afraid of the consequences (e.g., extra visits to the
pediatrician, shots, medicine).

Potential barriers to the effective treatment

of pain in children10

• The myth that children, especially infants, do not feel pain the WEB RESOURCES
way adults do; American Pain Society
www.ampainsoc.org
• Lack of routine assessment for the presence of pain in children;
National Children’s Pain Center
• The idea that treating pediatric pain takes too much time and www.pediatricpain.org/ncpc.php
effort;
Pediatric Pain Sourcebook
• Fears of adverse effects of analgesic medications, including http://painsourcebook.ca/
respiratory depression and addiction; UCLA Pediatric Pain Program
• Differing personal values and beliefs of healthcare professionals www.mattel.ucla.edu/pedspain/home.php
about the meaning and value of pain in the development of the American Academy of Pediatrics
child (e.g., the belief that pain builds character). http://www.aap.org

14 American Pain Foundation

 SPECIAL CONSIDERATIONS: PAIN IN SPECIFIC POPULATIONS Topic Brief

Gender and Pain

Although it has long been thought Female hormones are also likely Potential Sources of Gender
that women and men have similar to play a role in pain perception. Differences in Pain
pain experiences, recent research Some pain conditions like Biological factors including:
reveals significant differences in migraine tend to vary with a
• sex hormones
the way male and female brains woman’s menstrual cycle, and
process pain,1 as well as in many of the observed gender • genetics
women’s expression of pain and differences in pain appear to • anatomical differences
their responsiveness to analgesics diminish following the Psychosocial influences including:
and pain stimulus.2,3 reproductive years.8 • emotion (e.g., anxiety,
Historically, women have been Hormones May Influence depression)
categorized as being emotional Pain Experience • coping strategies
and overly sensitive; often
• Estrogen administration in • gender roles
influencing the way physicians
assessed and managed their pain.4 women and in men can increase • cultural conditioning
Even though research now shows the incidence of chronic pain • health behaviors
that chronic pain conditions are conditions.9,10
• use of healthcare services
generally more prevalent among • Variations in women’s estrogen
women, they continue to be levels, like those that occur As advances in brain imaging
treated less aggressively for their during the menstrual cycle or technology provide further insights
pain than men.5,6 And while during pregnancy, may regulate into gender variations in the
women are more likely than men the brain’s natural ability to experience of pain, it is becoming
to seek treatment for their pain, evident that different pain
suppress pain.11
they are less likely to receive it.7 experiences among men and
• Some pain conditions such as women will call for different
Women report pain more often migraine and fibromyalgia tend approaches to pain management.
than men do and in more body to fluctuate with a woman’s
regions, and they also tend to menstrual cycle. Ongoing research is essential to
have more severe, recurrent and achieve:
• Observed gender differences in
persistent pain, as well as a • A better understanding of the
pain appear to diminish
reduced pain threshold when biological and psychosocial
following menopause.
compared with men.3 However, factors that influence gender
despite their increased pain Additionally, cultural conditioning differences in pain
burden, women reportedly cope may impact the expression of pain • A greater appreciation of the
with pain better than men, among women and men. As different health needs of men
possibly due to the fact that they children, girls are more likely to
experience pain more often and women
be permitted to express pain and
throughout the course of their • More effective and targeted pain
show emotion than boys, and
lives (e.g., menstruation, treatments for women
attitudes about the social
pregnancy and child birth, and acceptability of gender and pain
other health issues specific to often carry into adulthood.3
women).3
WEB RESOURCES
PAIN DISORDERS WITH HIGHER PREVALENCE IN WOMEN International Association for the Study of
Pain: Real Women, Real Pain
• Migraine • Breast pain (mastalgia) www.iasp-pain.org

• Irritable bowel syndrome • Autoimmune disorders (e.g. Lupus National Institutes of Health: Gender & Pain
http://painconsortium.nih.gov/genderandpain/
• Fibromyalgia and Chronic Fatigue Syndrome) summary.htm
• Chronic pelvic pain • Rheumatoid arthritis National Women’s Health Resource Center
• Interstitial cystitis • Osteoarthritis www.healthywomen.org/
Society for Neuroscience: Gender & Pain
• Temporomandibular joint disorder
www.sfn.org/index.cfm?pagename=brainBriefing
(TMJ) s_gender_and_pain

A Reporter’s Guide: Covering Pain and Its Management 15

 Older Adults and Pain
As we age, pain becomes a more for inadequate pain management.
3
communicating their pain. Use
4

common problem due to the high of certain medications in older

prevalence of chronic and Diagnosing and treating pain in
older adults can be challenging. patients becomes problematic
progressive pain-producing because of physiological changes.
5

conditions associated with aging. Those 65 and older often present

It is estimated that up to 50% of with multiple medical and The most common cause of
older persons living in the nutritional problems, take multiple persistent pain in older adults is
community have pain that medications and have many musculoskeletal in nature, typically
interferes with normal function, potential sources of pain. from osteoarthritis or other bone,
and 59 to 80% of nursing home Older persons with dementia or joint and spine disorders.
residents experience persistent communication problems are at According to the Arthritis
1,2
pain. Alarmingly, being older even greater risk of undertreatment Foundation, arthritis affects up to
than 70 is the leading risk factor of pain due to difficulties 80% of older adults, who report
being fearful of recurring pain and
disability. But the predilection for
COMMON PAIN CONDITIONS IN OLDER ADULTS painful conditions does not mean
that older adults need to live with
• Arthritis uncontrolled pain. Quite the
• Lower back and neck pain; vertebral compression fractures from osteoporosis opposite; older patients can be
• Abdominal pain (e.g., gallstones, bowel obstruction, peptic ulcer disease, effectively treated, and in so doing,
abdominal aortic aneurysm) pain-related morbidity—and even
premature mortality—can and
• Cancer-related pain (symptom of disease or effect of nerve damage from should be obviated.
treatments)
• Neuropathic pain due to diabetes, herpes zoster (“shingles”), kidney disease or
other medical problems
• Muscle cramps, restless leg pain, itchy skin and sores due to circulatory
problems or vitamin D deficiency
• Fibromyalgia
• Complex Regional Pain Syndrome (CRPS), which develops after an illness or
injury and often affects the leg, arm, foot or hand
• Injuries, especially from falls

WEB RESOURCES
Handbook of Pain Relief in Older Adults —
An Evidence-Based Approach
By Gloth III, F. Michael
http://www.humanapress.com/Product.pasp?txt
Catalog=HumanaBooks&txtProductID=1-58829-
217-7
American Medical Association
Assessing and Treating Pain in Older Adults
http://www.ama-cmeonline.com/
pain_mgmt/module05/index.htm

American Geriatrics Society Foundation

The Management of Persistent Pain:
Resources for Older Adults and Caregivers
http://www.healthinaging.org/public_education/
pain

16 American Pain Foundation

 SPECIAL CONSIDERATIONS: PAIN IN SPECIFIC POPULATIONS Topic Brief

End-of-Life and Pain

Pain control is one of the most designed and aggressive
challenging aspects of end-of-life medication plans, as well as “S uicidal wishes in patients with
care.1 Terminal illness is often counseling for patients and their advanced disease are closely linked
accompanied by severe pain, and families can have a significant to unrelieved pain and to mood
a significant number of patients impact on pain relief and side4,5 alterations such as depression and
suffer needlessly at the end-of-life. effects among dying patients. anxiety, which like pain, frequently
While the goal of end-of-life care
should be making patients more
respond to clinician treatment
IN DYING PATIENTS, PAIN MAY BE
comfortable, the health care EXACERBATED BY MANY OTHER if the clinician identifies and
system has been designed to take
a curative approach to disease,
SYMPTOMS INCLUDING: addresses them. 2,6”
• Dry mouth
rather than focusing on symptom
relief.2 Hospital research reveals • Nausea
Essential Components of
that healthcare providers continue • Water retention and swelling End-of-Life Care
8

to inadequately treat pain, and • Lack of appetite • Continual assessment and

tend to under-medicate terminal
• Shortness of breath management of pain and other
pain.
• Mental distress and anxiety caused physical symptoms
Patients at end-of-life may have by fear or denial of impending death • Assessment and management
their pain undertreated for variety
of psychological and spiritual
of reasons, including a lack of
knowledgeable and experienced Effective pain management at the needs
physicians and myths about end-of-life requires addressing the • Helping patients identify
addiction to pain medication, total pain experience, including personal goals for pain
leading unnecessarily to patient physical causes, as well as 3,4 treatment and end-of-life care
and family suffering.3 interpersonal and spiritual pain.
• Assessment of the patient’s
Despite advances in research on Pain associated with terminal support system
end-of-life pain treatment, illness often requires special
physicians remain influenced by treatment that can be best
social and legal concerns, as well provided by hospice and palliative
as misconceptions about care programs available in many
medications including addiction, medical facilities. Hospice focuses
overdose, lasting side effects and on relieving symptoms and
diminished physical capacity.5 supporting patients who are
Patients and their families may nearing the end of their life, while
also hesitate to begin using pain palliative care is designed to
medications as they often associate provide comfort and pain relief at
any time during a person’s illness.7 WEB RESOURCES
such treatment with imminent
death, thereby allowing patient The goal of both programs is to American Academy of Family Physicians:
suffering to worsen and continue.4 alleviate suffering and ultimately Challenges in Pain Management at the End
assist patients in achieving a pain- of Life
However, thorough and ongoing free and dignified death. www.aafp.org/afp/20011001/1227.html
pain assessment, paired with well- American Pain Society: Treatment of Pain at
the End of Life
www.ampainsoc.org/advocacy/treatment.htm

“W hen someone is dying, time is a luxury and wait-and-see is not an option.

What matters most in the final days is that patients are free of crippling pain
Discovery Health Center: End of Life Q&A
with Dr. Scott Fishman
http://health.discovery.com/centers/pain/
and unbearable suffering so that they can finish their lives in ways that bring endoflife/endoflife.html
comfort, peace, and completion. Concerns about lasting side effects or National Hospice and Palliative Care
diminished physical capacity from months of using a drug become Organization
secondary to making a patient comfortable. No one has to die in pain. ” www.nhpco.org/i4a/pages/
index.cfm?pageid=3254
— Dr. Scott Fishman

A Reporter’s Guide: Covering Pain and Its Management 17

 Military/Veterans and Pain1
Pain is a major issue among military personnel and veterans, who are at heightened risk for injury and
combat wounds. Although today’s body armor and rapid evacuation to medical care is saving lives, there are
more maimed and shattered limbs than ever before, with instances of amputation double previous rates.
Hundreds of thousands of returning veterans will seek medical care and claim disability compensation for a
wide variety of injuries and health problems they endured during their tours of duty. It is estimated that the
U.S. will be paying the cost of related medical care and disability claims for the next 40 years.
Veterans are more likely to experience psychological distress and other medical conditions, including post
traumatic stress disorder, depression, amputations, traumatic brain injuries, substance abuse and other injuries,
which further complicate effective pain management.

COMMON PAIN CONDITIONS AMONG MILITARY MEMBERS

Post traumatic stress disorder (PTSD) Amputations have long been a tragic, A traumatic brain injury (TBI) is a blow
commonly affects soldiers returning from unavoidable consequence of combat or jolt to the head or a penetrating head
war, and is triggered by exposure to a injury—“one of the most visible and injury that disrupts the function of the
situation or event that is or could be enduring reminders of the cost of war,” brain and is a major cause of life long
perceived as highly threatening to a according to the Amputee Coalition of disability and death. Managing pain in
person’s life or those around him/her. America. While there have been major veterans with TBIs may be complicated
PTSD may not emerge for years after the advances in medicine, prosthetics and by memory lapses affecting medication
initial trauma. Chronic pain symptoms technologies that allow amputees to management, difficulty organizing and
and PTSD frequently co-occur and may lead more independent lives, most of following complicated and sometimes
intensify an individual’s experience of these patients continue to need even simple pain management regimens,
both conditions. Together, they result in specialized long-term or lifelong support. and difficulty learning new coping skills.
fear, avoidance behaviors, anxiety and Managing wound, post-operative, Rehabilitation should incorporate efforts
feelings of isolation. phantom and stump pain is important to to relieve associated pain.
reduce suffering and improve quality
of life.

Veterans have significantly worse pain than the general public, and while military medical care is among the best in the
world, there are still long-term problems and challenges with managing disability and chronic pain.

Military culture may also present a significant barrier to appropriate patient care. The persisting stigma around pain
and pain treatment is particularly pronounced in the military, and pain is often perceived as a sign of weakness
leading many individuals to choose to suffer in silence. Seeking mental health care for PTSD and depression, which
so often accompany pain is important; pain is best managed when depression and PTSD are treated simultaneously.
A recent analysis found that the Veterans Health Administration (VHA) is already overwhelmed by the sheer number
of returning veterans and the seriousness of their health care needs. Without increased staffing and funding for
veterans medical care, it will not be able to provide quality care in a timely fashion.

18 American Pain Foundation

 SPECIAL CONSIDERATIONS: PAIN IN SPECIFIC POPULATIONS Topic Brief

Military/Veterans and Pain1

Barriers to optimal pain management among veterans and military personnel may include
fears about:
• No longer being physically capable of fulfilling their duties
• Being discharged and no longer having a sense of purpose
• Letting down or losing the respect of their peers
• Becoming addicted to pain medications
• Experiencing personality changes or problems with sexual relations due to pain medications
• Losing their benefits/pension if they acknowledge a pain condition

THE UNITED STATES CONGRESS HAS STATED THE FOLLOWING:

(1) Acute and chronic pain are prevalent conditions among active duty and retired military personnel.
(2) Characteristics of modern warfare, including the use of improvised explosive devices, produce substantial numbers of
battlefield casualties with significant damage to both the central and peripheral nervous systems.
(3) The successes of military health care both on and off the battlefield result in high survival rates of severely injured
military personnel who will be afflicted with significant pain disorders on either an acute or chronic basis.
(4) Failure to treat acute pain promptly and appropriately at the time of injury, during initial medical and surgical care, and
at the time of transition to community-based care, contributes to the development of long-term chronic pain
syndromes, in some cases accompanied by long-term mental health and substance abuse disorders.
(5) Pain is a leading cause of short- and long-term disability among military personnel.
(6) The military health care systems have implemented important pain care programs at some facilities and in some areas,
but comprehensive pain care is not consistently provided on a uniform basis throughout the systems to all patients in
need of such care.
(7) Inconsistent and ineffective pain care leads to pain-related impairments, occupational disability, and medical and
mental complications with long-term costs for the military health and disability systems, and for society at large.
(8) Research, diagnosis, treatment, and management of acute and chronic pain in the active duty and retired military
populations constitute health care priorities of the United States.
From the Military Pain Care Act of 2008

WEB RESOURCES
American Pain Foundation:
Military/Veterans and Pain
T he U.S. Veterans Health Administration is instructing www.painfoundation.org/
page.asp?file=Veterans/Intro.htm
physicians and nurses who treat veterans to regard pain as
Amputee Coalition of America
a “fifth vital sign,” to be routinely assessed along with www.amputee-coalition.org
blood pressure, pulse, temperature and respiration. Defense and Veterans Brain Injury Center
www.dvbic.org
Disabled American Veterans (DAV)
www.dav.org
Military Pain Care Act of 2008
http://www.govtrack.us/congress/
bill.xpd?bill=h110-5465
U.S. Department of Veterans Affairs
www.va.gov

A Reporter’s Guide: Covering Pain and Its Management 19

 HOT TOPICS

Children & Pain: HOT TOPICS

• Maternal anxiety influencing daughters’ experience of pain
• Some neonatologists still do not treat pain in pre-term low birth weight
babies because they “won’t remember it”
• Investigations into “chronic daily headaches” in children
• Unraveling pediatric pain conditions and their impact into adulthood
(e.g., whether Complex Regional Pain Syndrome in children leads to
adult CRPS, whether irritable bowel syndrome in adolescents is this the
same as IBS in adults)
• Complementary and alternative medicine: how and what is safe to use
in children with chronic pain?
• Factors leading to pain-related disability in children (e.g., missing
school, not sleeping, avoiding physical and social activities, not eating)

Gender & Pain: HOT TOPICS

• Prevalent pain conditions in women (e.g., fibromyalgia, chronic pelvic
pain)
• Interface of hormones and the pain experience
• Brain imaging, uncovering routes of pain transmission and tolerance
• Differential effects of medicines across genders
• Impact of chronic pain on sexuality and self-image

20 American Pain Foundation

 SPECIAL CONSIDERATIONS: PAIN IN SPECIFIC POPULATIONS Topic Brief

HOT TOPICS

Older Adults and End-of-Life Care & Pain: HOT TOPICS

• False belief that pain is an inevitable part of aging
• Vitamin deficiencies and musculoskeletal pain
• Limited consumer awareness of the options that exist other than
traditional “acute care” approaches (e.g., doctor’s office visits, ER visits,
hospitalizations)
• Insufficient numbers of adequately trained and skilled healthcare
professionals to manage the myriad issues confronting patients/families
with advanced medical illness; limited number of providers with
specialty in geriatrics
• Variability in delivery of hospice and palliative care services across the
country
• Lack of clinical research data on pain care among elders

Military/Veterans & Pain: HOT TOPICS

• President Bush recently signing the Military and Veterans Pain Care Acts
into law
• Emerging Options: Interdisciplinary approaches to pain care
• Acupuncture now being incorporated into treatment plans at Walter
Reed Army Medical Center
• Competitive athletics as a form of therapy
• New Veteran centers open for drop-in counseling

A Reporter’s Guide: Covering Pain and Its Management 21

 References
Children and Pain 10. Aloisi AM, Bachiocco V, Costantino A, Stefani R, Ceccarelli I, et al.
1. Goodman, JE, McGrath, PJ. (1991). The epidemiology of pain in (2007) Crosssex hormone administration changes pain in
children and adolescents: A review. Pain, 46:247–264. transsexual women and men. Pain. [Epub ahead of print]
2. Zeltzer LK, Schlank CB. (2005) Conquering Your Child’s Chronic 11. Zubieta JK. “Systems Integration and Neuroimaging in the
Pain: A Pediatrician’s Guide for Reclaiming a Normal Childhood. Neurobiology of Pain” Presented February 18, 2003 at the
New York, NY: HarperCollins. American Association for the Advancement of Science annual
meeting.
3. Chronic Abdominal Pain in Childhood: Diagnosis and
Management. Retrieved October 12, 2008 from American Older Adults and Pain
Academy of Family Physicians. Web site: 1. Ferrell BA. (1995). Pain evaluation and management in the
http://www.aafp.org/afp/990401ap/1823.html nursing home. Ann Intern Med, 123:681-687.
4. Juvenile Arthritis. Retrieved October 13, 2008 from American 2. Helme RD, Gibson SJ. Pain in Older People. In: Crombie IK, ed.
Academy of Orthopaedic Surgeons. Web Epidemiology of Pain. Seattle: IASP Press; 1999:103-112.
site:http://orthoinfo.aaos.org/topic.cfm?topic=A00075
3. Cleeland, CS, Gonin R, Hatfield AK, Edmonson JH, et al. (1994)
5. Nemours Foundation. Growing Pains Fact Sheet. Retrieved Pain and Its Treatment in Outpatients with Metastatic Cancer. N
October 13, 2008 from http://kidshealth.org/parent/general/ Engl J Med, 330(9):592-596.
aches/growing_pains.html.
4. Parmalee PA, Smith B, Katz IR. (1993). Pain complaints and
6. Tsao JCI, Lu Q, Kim SC, Zeltzer LK. (2006). Relationships among cognitive status among elderly institution residents. J Am Geriatr
anxious sympto-matology, anxiety sensitivity and laboratory pain Soc, 41:517-22.
responsivity in children. Cognitive Behaviour Therapy, 35:207-215.
5. Schmucker DL. (2001) Liver Function and Phase I Drug
7. Zeltzer LK, Anderson CTM, Schechter NL. (1990) Pediatric Pain: Metabolism in the Elderly: A Paradox. Drugs Aging, 18:837-851.
Current status and new directions. Current Problems in Pediatrics,
20(8):415-486. End-of-Life and Pain
8. Anand KJS. (2006). Fetal pain. Pain-Clinical Updates, 14:1-4. 1. Challenges in Pain Management at the End of Life. Retrieved
9. Foley KM. (1996) Controlling the pain of cancer. Sci Am, 275(3): October 13, 2008 from American Academy of Family Physicians.
164-165. Web site: http://www.aafp.org/afp/20011001/1227.html
10. The Assessment and Management of Acute Pain in Infants, 2. Treatment of Pain at the End of Life: A Position Statement from
Children, and Adolescents: A Position Statement from the the American Pain Society. Retrieved October 12, 2008 from
American Academy of Pediatrics Committee on Psychosocial American Pain Society. Web site: http://www.ampainsoc.org/
Aspects of Child and Family Health and American Pain Society advocacy/treatment.htm
Task Force on Pain in Infants, Children, and Adolescents. 3. Pain Management at the End of Life: A Physician’s Self-Study
Retrieved October 12, 2008 from American Pain Society. Web site: Packet. Retrieved October 12, 2008 from Maine Hospice Council.
http://www.ampainsoc.org/advocacy/pediatric2.htm Web Site: http://www.mainehospicecouncil.org/
Pain%20Management%20web%20version.pdf
Gender and Pain
4. Leleszi JP, Lewandowski JG. (2005) Pain Management in End-of-
1. Paulson PM, Minoshima S, Morrow TJ, Casey KL. (1998) Gender Life Care. J Am Osteopath Assoc, 105(3_suppl), 6S-11.
differences in pain perception and patterns of cerebral activation
during noxious heat stimulation in humans. Pain, 76:2239. 5. Pain Mangement: Q&A with Dr. Scott Fishman. Retrieved
October 12, 2008 from Discovery Health. Web site:
2. Fillingim RB, Maixner W. (1995) Gender differences in the http://health.discovery.com/centers/pain/endoflife/endoflife.html
response to noxious stimuli. Pain Forum,4:209-21.
6. Foley KM. (1995) A review of ethical and legal aspects of
3. Berkley KJ. (1997) Sex differences in pain. Behav Brain Sci, terminating medical care. Amer J Med, 84:291-301.
20:371-80.
7. End-of-Life Care. Retrieved October 12, 2008 from National
4. Fishbain DA, Goldberg M, Meagher BR, et al. (1986) Male and Hospice and Palliative Care Organization. Web site:
female chronic pain patients categorized by DSM-III psychiatric http://www.nhpco.org/i4a/pages/index.cfm?pageid=3254
diagnostic criteria. Pain, 26(2):181-97.
8. End-of-Life Care Eases Pain and Prepares Patient for Death.
5. LeResche L. (1999) Gender considerations in the epidemiology of Retrieved October 12, 2008 from Medical College of Wisconsin.
chronic pain. Chapter in I. Crombie (ed.), Epidemiology of Pain. Web site: http://healthlink.mcw.edu/article/1001710698.html
IASP Press, Seattle.
6. Green CR. “Pain, Disparities, and Practice: Opportunities to Military/Veterans and Pain
Improve Health Policy and Healthcare Quality,” Presented 1. Military/Veterans and Pain Fact Sheet. Retrieved October 13,
September 9, 2008 at the American Academy of Pain 3008 from the American Pain Foundation.
Management annual meeting. Web site: www.painfoundation.com.
7. Hoffmann DE, Tarzian AJ. (2001) The Girl Who Cried Pain: A
Bias Against Women in the Treatment of Pain. J Law Med Ethics,
29:13-27.
8. Gagliese L, Fillingim RB. (2003) Age and sex interactions in the
experience of pain. XX vs. XY: The International Journal of Sex
Differences in the Study of Health, Disease and Aging 1,124131.
9. Dao TT, LeResche L. (2000) Gender differences in pain. J Orofac
Pain, 14: 169184.

22 American Pain Foundation

 Topic Brief
PAIN MANAGEMENT & DISPARITIES
The undertreatment of pain in America is a growing public health crisis,
especially among underserved populations, including ethnic minorities, women,
the elderly and those who are socioeconomically disadvantaged. Despite an
overall improvement in health for most Americans, certain segments of the “Of all the forms of
population continue to experience poor health status.1 There is compelling inequality, injustice in
evidence that minorities are less likely to have access to routine, coordinated
medical care or health insurance than whites. They are also more likely to health is the most shocking
receive inappropriate or insufficient care, resulting in poorer health outcomes. and the most inhumane.”
As the U.S. population becomes increasingly diverse, there is an urgent need to
eliminate health disparities. Patients have a right to appropriate assessment and –Martin Luther King, Jr.
treatment of their pain without regard to race, ethnicity or other factors.

Health Disparities Defined

Snapshot of U.S. Population,
According to the National Institutes of Health, health disparities are An Older and More Diverse
defined as “differences in the incidence, prevalence, mortality, and Nation
burden of diseases and other adverse health conditions that exist
among specific population groups in the United States.” According to projections by the U.S.
Census Bureau:
Disparities in health care are complex and multifaceted resulting • Minorities now comprise roughly
from: one-third of the U.S. population.
• Patient/personal factors (e.g., low socioeconomic status, • By 2023, more than half of all
communication barriers) children will be from minority
• Healthcare provider factors (e.g., bias, cultural insensitivity) groups.
• Systematic/health system factors (e.g., health insurance status, • Minorities are expected to become
access to care) the majority in 2042.
• In 2050, the nation is projected to
be 54% minority.
• The Latino population, already the
nation’s largest minority group,
will triple in size between 2005
and 2050.
• The nation’s elderly population
will more than double in size
from 2005 through 2050 as the
baby boom generation enters
traditional retirement years.

Source: U.S. Census Bureau, 2008,

http://www.census.gov/PressRelease/www/
releases/archives/population/012496.html;
Pew Hispanic Center.

A Reporter’s Guide: Covering Pain and Its Management 23

 Disparities in Pain Care RESEARCH ON DISPARITIES IN PAIN CARE HAVE SHOWN:
Pain is widely recognized as an • Blacks were less likely than whites to receive pain medication and had a 66%
undertreated health problem in the greater risk of receiving no pain medication at all.5,6,7,9
general population.2 However, a
• Hispanics were twice as likely as non-Hispanic whites to receive no pain
growing body of research reveals
medication in the emergency department (55% of Hispanics received no pain
even more extensive gaps in pain
medication vs. 26% of non-Hispanic whites).7,10
assessment and treatment among
racial and ethnic populations, with • Minority patients were less likely to have pain recorded relative to whites, which
minorities receiving less care for is critical to providing quality patient care.11
pain than non-Hispanic whites.3,4,5,6, • Only 25% of pharmacies in predominantly nonwhite neighborhoods had opioid
Differences in pain care occur supplies that were sufficient to treat patients in severe pain, as compared with
across all types of pain (e.g., acute, 72% of pharmacies in white neighborhoods.12
chronic, cancer-related) and • In a study of minority outpatients with recurrent or metastatic cancer, 65% did
medical settings (e.g., emergency not receive guideline-recommended analgesic prescriptions compared with 50%
departments and primary care).3,4,5,6,7 of nonminority patients (P < 0.001). Hispanic patients in particular reported less
Even when income, insurance pain relief and had less adequate analgesia.13
status and access to health care are
accounted for, minorities are still
less likely than whites to receive treatment of pain. Most chronic Organization has declared that
necessary pain treatments.3,4,8 pain conditions are more prevalent pain relief is a human right.
among women; however, women’s
Minorities are less likely to: Patient and provider factors
pain complaints tend to be poorly
drive pain disparities
• Have access to pain assessed and undertreated.3
management services and Multiple factors contribute to racial
Additionally, gender differences
treatments and ethnic disparities in pain care,
have been identified in patient
including beliefs about pain,
• Have their pain documented by responsiveness to analgesics and
preconceived bias and cultural
healthcare providers pain stimuli. While estrogen and
insensitivity and poor patient-
• Receive pain medications progesterone play a role in how
provider communication.
pain signals are received in men
And more likely to: Positive physician-patient
and women, psychology and
• Use the emergency department culture may also account for some interaction and communication is
for pain care, but less likely to of the difference. For example, critical in accurate pain
receive adequate care children may learn how to assessment.2 Some research has
• Experience greater severity of respond to pain later in life shown that patients take a more
pain depending on how their pain active role in their own pain
• Experience and report physical complaints were treated in their treatment when their healthcare
formative years (e.g., receiving providers are of similar ethnic
disability
comfort and validation versus backgrounds.3,4
• Experience poorer health and being encouraged to tough it out
quality of life related to pain or dismiss the pain).14 For more
information, see the Special
There are clear variations in the
way pain is assessed and managed
Considerations: Pain in Specific “Pain is a complex, subjective
Populations Topic Brief. response with several quantifiable
among all minority populations.
Significant gaps exist in the In response to the overwhelming features, including intensity,
discrepancies in pain treatment time course, quality, impact,
provision of effective quality pain
among minority groups, the Joint
care due to the lack of research
Commission issued a statement
and personal meaning. The
and medical training focused on reporting of pain is a social
recognizing the rights of all
pain care disparities.3,4,9 patients to receive appropriate transaction between caregiver
Research also shows gender
differences in the experience and
assessment and management of
pain, and the World Health
”
and patient. 15

24 American Pain Foundation

 PAIN MANAGEMENT & DISPARITIES Topic Brief

Patient sources of racial and ethnic Minorities lack access to Americans, including 9 million
disparities:3 effective pain care children, are living without health
• Low socioeconomic status Limited access to pain care services care coverage. More than eight out
• Patients’ attitudes or beliefs is a key contributor to poorer pain of 10 are from working families.
regarding pain and patient-level treatment among minorities. The consequences of being
decision making and preferences uninsured are widely recognized
• Overall, minorities tend to be and include: lack of access to
– Stoicism and the belief that financially poorer than non-
pain is an inevitable part of health care, poor quality care, lost
Hispanic whites. economic productivity, as well as
disease
• Socioeconomic factors can financial burdens on individuals
• Minority patients more likely to:
impede access to health and society overall. As the minority
– Refuse recommended pain insurance and primary health population in the U.S. continues to
therapies care services, and minorities are grow, it becomes increasingly
– Poorly adhere to treatment less likely to have access to pain important to address the numbers
regimens treatment services than the of uninsured and underinsured
– Delay seeking medical care general population.3,4,7,16,17 among racial and ethnic groups.
• Mistrust of physicians or • Racial and ethnic minorities are Barriers also exist in patient access
previous negative experiences at increased risk of having their to pain medications. Research
with health care system pain complaints ignored by shows that physicians may be less
• Limited health literacy healthcare providers, thereby likely to prescribe pain
• Language barriers that hinder limiting their options for medications for minority
communication with providers accessing appropriate pain populations 6,7,16,18 and pharmacies
treatment.3,4,6,7 in neighborhoods with large
Physician sources of racial and
According to the Robert Wood minority populations often do not
ethnic disparities:3
Johnson Foundation, 46 million carry opioid medications.3,4,12
• Perceptions of race and ethnicity
• Racism or bias
PERCENTAGE UNINSURED AMONG THE NONELDERLY POPULATION
• Poor cross cultural BY RACE AND ETHNIC ORIGIN, 2006
communication skills/cultural
insensitivity
• Underrepresentation of 35.7%

physicians from
racially/ethnically diverse
backgrounds/lack of cultural
sensitivity 21.8%
17.8%

HOT TOPICS 12.6%

Disparities & Pain: HOT TOPICS

• Aging and increasingly diverse U.S.
population could lead to greater White Black Hispanic Other

disease burden if pain remains Sources: Employee Benefit Research Institute estimates from the March Current
Population Survey, 2007 Supplement. Cover the Uninsured, www.covertheuninsured.org.
untreated
• Undertreatment of minorities in
emergency departments
“Inequities in access can contribute to and exacerbate
• Minority pain complaints receive less
attention than others existing disparities in health and quality of life, creating
• Impact of pain on productivity and barriers to a strong and productive life.”
quality of life among minority patients
—The Commonwealth Fund
• Pain relief as a human right

A Reporter’s Guide: Covering Pain and Its Management 25

 More extensive research needed Additional studies and a
to close disparities gap comprehensive pain research
While national attention has agenda are needed to:
become increasingly focused on • Understand the role of
WEB RESOURCES
health disparities, less attention has stereotypes and bias in doctor-
CDC Office of Minority Health and Health
been given specifically to patient interactions Disparities
inequities in pain care.19,20 • Improve training for healthcare http://www.cdc.gov/omhd/
However, the growing interest in providers Cover the Uninsured: a Project of the Robert
health disparities in general • Plan educational interventions
Wood Johnson Foundation
http://covertheuninsured.org/
provides pain treatment providers, for patients
researchers and advocates with an American Pain Society: Racial and Ethnic
• Understand the differences in Identifiers in Pain Management: The
opportunity to raise awareness Importance to Research, Clinical Practice,
patient behaviors that may
about disparities in pain and Public Health Policy
contribute to pain care disparities http://www.ampainsoc.org/advocacy/
management and the need for
additional pain disparities research. • Develop culturally sensitive pain ethnoracial.htm

Currently, the social impact of pain assessment tools Agency for Healthcare Research and Quality:
Addressing Racial and Ethnic Disparities in
on patients, their families and • Raise consciousness about Health Care
communities is largely absent in disparities in pain management http://www.ahrq.gov/research/disparit.htm
most federal research plans.3,4 and barriers to effective http://www.ahrq.gov/qual/nhdr03/
nhdrsum03.htm
healthcare overall

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2. Bonham VL. (2001). Race, Ethnicity, and Pain Treatment: Striving to Understand the Causes and Solutions to the Disparities in Pain
Treatment. Journal of Law, Medicine & Ethics, 129:52.
3. Green CR. (2003). The Unequal Burden of Pain: Confronting Racial and Ethnic Disparities in Pain. Pain Medicine, 4(3):277-294.
4. Green C. (2006). Disparities in Pain: Ethical Issues. Pain Medicine, 7(6):530-533.
5. Todd KH, Ducharme J, Choiniere M, Crandall CS, Fosnocht D, Homel P, et al. (2007). Pain in the Emergency Department: Results of the Pain
and Emergency Medicine Initiative (PEMI) Multicenter Study. The Journal of Pain, 8(6):460-466.
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271(12):925-28.
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8. Paulson MR, Dekker AH, Aguilar-Gaxiola S. (2007). Eliminating Disparities in Pain Management. J Am Osteopath Assoc, 107(suppl_5), ES17-20.
9. Freeman HP, Payne R. (2000) Racial injustices in health care. New Engl J Med, 342(14):1045-1047.
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11. Karpman, et al. (1997) Analgesia for emergency centers’ orthopaedic patients: does an ethnic bias exist?, Clinical Orthopaedics and Related
Research, 334:270-5.
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N Engl J Med, 342:1023-1026.
13. Cleeland CS, Gonin, R, Baez, L, Loehrer, P, & Pandya, KJ. (1997). Pain and Treatment of Pain in Minority Patients with Cancer: The Eastern
Cooperative Oncology Group Minority Outpatient Pain Study. Ann Intern Med, 127(9):813-816.
14. Pain: Hope through Research. Retrieved October 12, 2008 from National Institute of Neurological Disorders and Stroke (NINDS). Web site:
http://www.ninds.nih.gov/disorders/chronic_pain/detail_chronic_pain.htm
15. Dalton J. (1998). A call for standardizing the clinical rating of pain intensity using a 0 to 10 rating scale. Cancer Nursing, 21(11):46–49.
16. Lebovits A. (2005) The ethical implications of racial disparities in pain: Are some of us more equal? Pain Med; 6:3-4.
17. Payne R, et al. (2002) Quality of Life Concerns in Patients with Breast Cancer. Cancer, 97:311-317.
18. Ng, Dimsdale, Shragg, et al. (1996) Ethnic differences in analgesic consumption for postoperative pain. Psychosomatic Medicine, 58:125-9.
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Statement from the American Pain Society. Approved by the APS Board of Directors, October 22, 2004. Retrieved October 12, 2008 from
American Pain Society. Web site: http://www.ampainsoc.org/advocacy/ethnoracial.htm
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Web site: http://www.iom.edu/?id=16740

26 American Pain Foundation

 Topic Brief
CHRONIC PAIN AND OPIOID TREATMENT
Effective management of chronic pain often requires a step-wise trial of different treatment options, a team of healthcare
providers and social support from family and friends. Healthcare providers may start with behavioral and non-pharmacological
interventions (e.g., hot/cold therapy, physical therapy, relaxation techniques) when devising pain treatment plans. However, pain
relievers, including prescription pain medicines (opioid analgesics), are often prescribed to help alleviate pain and improve
function.

Key Issues
• More than 76.5 million Americans suffer with pain.1 The consequences of unmanaged chronic pain are devastating for
patients. It is not uncommon for patients with intractable, debilitating pain—many of whom are often made to feel that the
pain is “just in their heads”—to want to give up rather than living one more day in excruciating pain.
• For many patients, opioids are an integral part of a comprehensive pain management plan to help relieve pain, restore
functioning and improve quality of life.2,3
• Unfortunately, patient access to these medications may be hindered by unbalanced state policies, persisting social stigma
surrounding their use, as well as therapeutic switching and/or step therapies imposed by insurance companies.
• Unless a patient has a past or current personal or family history of substance abuse, the likelihood of addiction is low when
opioids are taken as prescribed and under the guidance of a physician; however, they have the potential for misuse, abuse
and diversion.
• Rising rates of prescription drug abuse and emergency room admissions related to prescription drug abuse, as well as an
increase in the theft and illegal resale of prescription drugs, indicate that drug diversion is a growing problem nationwide.4
The main source of drug diversion is unlikely the prescriber as was once assumed, but rather from theft by family, friends and
workers in the home or from the sharing and selling of medications though often with good intentions.5
• Diverse players (e.g., lawmakers, educators, healthcare providers, the pharmaceutical industry, caregivers) must come
together to address the dual public health crises of the undertreatment of pain and rising prescription drug abuse.6
• Alleviating pain remains a medical imperative—one that must be balanced with measures to address rising non-medical
use of prescription drugs and to protect the public health.6

Opioids 101
Opioids include morphine, oxycodone, oxymorphone, hydrocodone, hydromorphone, methadone, codeine
and fentanyl. Opioids are classified in several ways, most commonly based on their origin and duration of
effects.7

Common classifications for opioids7,8

SOURCE Natural or semisynthetic: Synthetic: Synthesized in the laboratory

Contained in or slightly modified
(semisynthetic) from chemicals found
in poppy resin

DURATION OF RESPONSE Short-acting: Provide quick-acting Long-acting: Provide longer duration

pain relief and are used primarily as of pain relief and are most often
“rescue medication,”as in acute pain used for stable, chronic pain

A Reporter’s Guide: Covering Pain and Its Management 27

 One of the advantages of opioids use, the clinical profile of opioids nausea and vomiting, and other
is that they can be given in so has been very well characterized. gastrointestinal effects. Tolerance to
many different ways. For example, Multiple clinical studies have nausea and vomiting usually
they can be administered by shown that long-acting opioids, in develops within the first few days
mouth, rectal suppository, particular, are effective in or weeks of therapy, but some
intravenous injection (IV), improving: patients are intolerant to opioids
subcutaneously (under the skin), • Daily function and experience severe adverse
transdermally (in the form of a side effects.8 Other side effects
patch) or into a region around the • Psychological health include drowsiness, mental
spinal cord. Patches, IV injections • Overall health-related quality of clouding and, in some people,
and infusions are very important life for patients with chronic euphoria.7 Recent research shows
for patients who cannot swallow, pain 10 that genetic variations may
or whose GI tracts are not working influence opioid metabolism.
However, some types of pain, such
normally.9 Depending on the amount taken,
as pain caused by nerve
Opioids are believed to work by compression or destruction, do not opioids can depress breathing. The
binding to specific proteins (opioid appear to be relieved by opioids.8 risk of sedation and respiratory
receptors), which are found in depression is heightened when
specialized pain-controlling regions opioids are taken with other
of the brain and spinal cord. When Adverse Effects sedating medications (e.g.,
these compounds attach to certain Side effects of opioids result antihistamines, benzodiazepines),
opioid receptors, the electrical and primarily from activation of opioid reinforcing the need to carefully
chemical signals in these regions receptors outside and within the monitor patients. However, this
are altered, ultimately reducing nervous system. Activation of effect is usually is not present after
pain.7 opioid receptors in the gut, for a patient has taken opioids
Because of their long history of example, may cause constipation, regularly.

Careful Monitoring of and Open Communication with Patients

Patients taking opioids must be carefully selected and monitored, and should speak openly with their
healthcare provider about noticeable improvements in functioning, as well as side effects and other concerns
(e.g., constipation, fears of addiction).

Analgesia – Is the pain relief clinically significant? Is there a reduction in the pain
score (0-10)?
Activity levels – What is the patient’s level of physical and psychosocial functioning?
The Has treatment made an improvement?
Adverse effects – Is the patient experiencing side effects from pain relievers? If so,
Four are they tolerable?
“A’s” Aberrant behaviors – Are there any behaviors of concern such as early refills or lost
medication? Does the patient show signs of misuse, abuse or addiction? What is the plan
of action?
Source: Passik & Weinreb, 1998; Passik & Portenoy, 1998

The American Pain Foundation’s Target Chronic Pain materials help facilitate open dialogue between patients
and their healthcare team, and give prescribers tools for selecting, monitoring and following patients. To access
these resources, visit www.painfoundation.org and click on the Publications tab.

28 American Pain Foundation

 CHRONIC PAIN AND OPIOID TREATMENT Topic Brief

Dual Public Health Crises: Picture of Prescription Drug Abuse in America

Balancing Medical Imperative to
Relieve Suffering and Protect • An estimated 2.2 million Americans abused pain medications for the first time in
Public Safety 2006.12 The rate of new abuse of opioids has risen most dramatically among
teenagers.
Pain affects more Americans than
diabetes, heart disease and cancer • Between 1992 and 2002, reported abuse by teenagers increased by 542%.13
combined, and it is one of the • From 1999 to 2004, unintentional poisoning deaths associated with opioids and
leading causes of disability in the hallucinogens rose by 55%, and the increase has been attributable primarily to
United States. Recognition of pain prescription pain relievers.14
as a growing public health crisis
has led to the establishment of • According to 2005 and 2006 National Surveys on Drug Use and Health, an annual
specialized pain clinics, treatment national average of 6.2% of persons aged 12 or older had used a prescription
guidelines for certain types of pain, psychotherapeutic drug non-medically in the 12 months leading up to the survey;
as well as greater use of treatment an average of 9.1% of youths aged 12 to 17 were past year non-medical users of
strategies to effectively alleviate any prescription psychotherapeutic drug.12
pain and improve functioning, • Nearly 600,000 emergency department visits involved non-medical use of
including prescription pain prescription or over-the-counter (OTC) pharmaceuticals or dietary supplements.
medicines. Opiates/opioid analgesics accounted for 33% of the non-medical visits. Anti-
As the therapeutic use of opioids anxiety agents (sedatives and hypnotics) accounted for 34% of the non-medical
has increased to appropriately visits.4
address pain, there has been a
simultaneous and dramatic rise in
The growing prevalence of sometimes false—picture of chronic
non-medical use of prescription
prescription drug abuse not only pain management.6 Over time,
drugs.11 When abused—that is,
threatens the lives of abusers; these reports overshadow untold
taken by someone other than the
concerns about misuse, abuse and stories of people with pain—those
patient for whom the medication
diversion may also jeopardize whose lives have been shattered by
was prescribed, or taken in a
effective pain management by unrelenting pain—who get needed
manner or dosage other than what
impeding patient access to opioids. pain relief from these medications.
was prescribed—prescription
Fear of scrutiny by regulators or Understanding the difference
medications can produce serious
law enforcement, and specific between tolerance, physical
adverse health effects and can
action by some agencies, has had a dependence, abuse and addiction
lead to addiction, overdose and
“chilling effect” on the willingness is also critical to telling the story
even death.
of some doctors, nurse practitioners (See page 31-32 for definitions).
People who abuse opioids typically and physician assistants to According to medical experts, use
do so for the euphoric effects (e.g., prescribe opioids.6,15 of the term “narcotic” in news
the “high”); however, most abusers reports may further reinforce the
Moreover, high profile reports of
are not patients who take opioids myths and misconceptions of this
drug abuse, diversion and
to manage pain.12 Rather, they are class of drugs, given the negative
addiction, or of legal actions taken
often people within the social connotation.6
against prescribers have helped
network of the patient. In fact, 71%
perpetuate a negative—and
of people abusing prescription pain
relievers received them from a
friend or family member without a
prescription.5 Prescription pain
relievers are usually stolen from
“…[T]he attitude toward opioids has ranged from complete avoidance
to widespread therapeutic use with minimal caution. These extremes
medicine cabinets, purchased or
have been driven by insufficient appreciation of risks by those at one
shared in schools, or simply given
away. end of the spectrum, and excessive fear of punitive regulatory scrutiny
or exaggerated perceptions of addictive risk by those at the other.
When opioids are prescribed for pain control in adequately evaluated,
selected, and monitored patients, addiction is rare. ”
— Perry Fine, Topics in Pain Management

A Reporter’s Guide: Covering Pain and Its Management 29

 Strategies to Address Twin Public Health Crises
Systematic and targeted approaches are essential to address the growing prevalence and complexity of
prescription drug abuse, while simultaneously ensuring that people with legitimate medical needs receive
effective treatment.

These approaches can generally be plan (e.g., treatment agreements, For additional recommendations,
categorized as follows: urine testing and monitoring, see the American Pain
• Legislative strategies to create transition planning, collaborative Foundation’s report outlining
balanced and consistent practice with addiction medicine critical barriers to appropriate
regulation and improve state- and behavioral health opioid prescribing for pain
based prescription drug specialists). management, Provider Prescribing
monitoring programs. • Pharmaceutical industry Patterns and Perceptions:
• Educational efforts to raise strategies to help prevent misuse, Identifying Solutions to Build
awareness about prescription abuse and diversion by Consensus on Opioid Use in Pain
drug abuse and its dangers developing new tamper resistant Management. This 16-page report
among schools, families, packaging and/or formulations calls for a more balanced
healthcare providers, patients (e.g., tamper-resistant bottles, perspective of the risks and
and potential abusers. electromagnetic chips to track benefits of these medications in
medication, new formulations practice and policy and
• Medical strategies to help
that could resist or deter summarizes key challenges and
identify and monitor patients
common methods of opioid actionable solutions discussed by
who require opioid
abuse). leading pain experts at a
management, to include the
roundtable meeting hosted by APF.
incorporation of risk
management into the treatment

State Grades for 2008

Making the Grade: Evaluation State 2008 Grade State 2008 Grade
of State Policies Alabama B+ Montana C+
The Pain & Policy Studies Group Alaska C+ Nebraska B+
Arizona B+ Nevada C
(PPSG) report “Achieving Balance Arkansas B New Hampshire B
in State Pain Policy: A Progress California B New Jersey C+
Report” graded states on quality of Colorado B New Mexico B+
its policies affecting pain treatment Connecticut B New York C
and centered on the balance Delaware C+ North Carolina B
District of Columbia C+ North Dakota B
between preventing abuse, Florida B Ohio B
trafficking and diversion of Georgia B Oklahoma C+
controlled substances and Hawaii B Oregon A
simultaneously ensuring the Idaho B Pennsylvania C+
availability of these medications for Illinois C Rhode Island B+
Indiana C+ South Carolina C+
legitimate medical purposes. PPSG Iowa B South Dakota B
researchers evaluated whether Kansas A Tennessee C
state pain policies and regulations Kentucky B Texas C
enhance or impede pain Louisiana C Utah B+
management and assigned each Maine B+ Vermont B+
Maryland B Virginia A
state a grade from ‘A’ to ‘F.’ Massachusetts B+ Washington B+
Michigan A West Virginia B
Minnesota B+ Wisconsin A
Mississippi C+ Wyoming C+
Missouri C+
Source: The Pain & Policy Studies Group,
http://www.painpolicy.wisc.edu/Achieving_Balance/PRC2008.pdf.

30 American Pain Foundation

 CHRONIC PAIN AND OPIOID TREATMENT Topic Brief

At a Glance: Differentiating physical dependence, tolerance, abuse and addiction

Unfortunately, confusion between normal physiological responses to opioids (physical

dependence and tolerance) and pathological phenomena such as addiction or abuse persist. Such
misunderstandings not only reinforce the stigma surrounding legitimate medical use of these
medicines, they also fuel fears of addiction and, in turn, may impinge on patient access to these
medications. Although the use of opioids carries some risk of addiction, clinical studies have
shown that the potential for addiction is low for the vast majority of patients using opioids for
the long-term management of chronic pain.17 As with any medication, there are risks, but these
risks can be managed.

Physical dependence is Addiction is a disease

characterized by biological changes characterized by preoccupation
that lead to withdrawal symptoms with and compulsive use of a
(e.g., sweating, rapid heart rate, substance, despite physical or
nausea, diarrhea, goosebumps, psychological harm to the person
anxiety) when a medication is or others.3 Behaviors suggestive of
discontinued, and is not related to addiction may include: taking
addiction. Physical dependence multiple doses together, frequent
differs from psychological reports of lost or stolen
dependence, or the cravings prescriptions, and/or altering oral
for the euphoria caused by formulations of opioids.
opioid abuse. Symptoms of Abuse is the intentional self-
physical dependence can often administration of a medication for
be ameliorated by gradually a non-medical purpose, such as to
decreasing the dose of obtain a high.3 Both the intended
medication during patient and others have the
“Universal agreement discontinuation.7 potential to abuse prescription
on definitions of Tolerance is a biological process drugs; in fact, the majority of
in which a patient requires people who abuse opioids do not
addiction, physical suffer from chronic pain.12
increasing amounts of a
dependence and medication to achieve the same Pseudo-addiction describes
tolerance is critical to amount of pain relief. Dose patient behaviors that may occur
escalations of opioid therapies are when pain is undertreated. Patients
the optimization of sometimes necessary and reflect a with unrelieved pain may become
pain treatment and the biological adaptation to the focused on obtaining medications
management of medication. Although the exact and may otherwise seem
mechanisms are unclear, current inappropriately “drug seeking,”
addictive disorders.” research indicates that tolerance to which may be misidentified as
— Consensus document from opioid therapy develops from addiction by the patient’s
the American Academy of Pain changes in opioid receptors on the physician. Pseudo-addiction can be
Medicine, the American Pain surface of cells.7 Thus, the need for distinguished from true adduction
Society and the American Society higher doses of medication is not in that this behavior ceases when
of Addiction Medicine necessarily indicative of addiction.3 pain is effectively treated.3

A Reporter’s Guide: Covering Pain and Its Management 31

 MISUSE VS. ABUSE?
• Medical Misuse: Legitimate use of a valid personal prescription but using differently from provider’s instruction, such as
taking more frequently or higher than the recommended doses. Use may be unintentional and considered an educational
issue.
• Medical Abuse: Valid personal prescription by using for reasons other than its intent, such as to alleviate emotional
stress, sleep restoration/prevention, performance improvement, etc. Use may be unintentional and considered an
educational issue.
• Prescription Drug Misuse: Intentional use of someone else’s prescription medication for the purpose of alleviating
symptoms that may be related to a health problem. The use may be appropriate to treat the problem but access to obtain
this drug may be difficult/untimely or may have been provided from a well-intentioned family member or friend.
• Prescription Drug Abuse: Intentional use of a scheduled prescription medication to experiment, to get high or to create
an altered state. Access to the source may be diversion from family, friends or obtained on the street. Inappropriate or
alteration of drug delivery system, used in combination of other drugs or used to prevent withdrawal from other
substances that are being abused are included in this definition.
Source: Carol J. Boyd PhD, MSN, RN; Director: Institute for Research on Women and Gender, Substance Abuse Research Center,
University of Michigan

Risk factors for opioid misuse include, but are not limited to:2,3,19
• Personal or family history of prescription drug or alcohol abuse
• Cigarette smoking
• History of motor vehicle accidents
• Substance use disorder
• Major psychiatric disorder (e.g., bipolar disorder, major depression,
personality disorder)
• Poor family support
• History of preadolescent sexual abuse

NOTE: Unless a patient has a past or current history of substance

abuse, the potential for addiction is low when opioid medications
are prescribed by a doctor and taken as directed. Those patients
who suffer with chronic pain and addictive disease deserve the
same quality of pain treatment as others, but may require greater
resources in their care. WEB RESOURCES
Opioid RX
http://pain-topics.org/
opioid_rx/#RiskManage
Tufts Health Care Institute Program on
Opioid Risk Management
http://www.thci.org/opioid/
Opioid Risk Management PainEDU
http://www.painedu.org/soap.asp
Emerging Solutions
http://www.emergingsolutionsinpain.com/i
ndex.php?option=com_frontpage&Itemid=1

32 American Pain Foundation

 CHRONIC PAIN AND OPIOID TREATMENT Topic Brief

REFERENCES
1. National Center for Health Statistics. Health, United States, 2006 With Chartbook on Trends in the Health of Americans. Hyattsville, MD.
Available at http://www.cdc.gov/nchs/data/hus/hus06.pdf.
2. Fine, PG. Opioid Therapy as a Component of Chronic Pain Management: Pain Experts Weigh In on Key Principles to Optimize Treatment.
Topics in Pain Management. May 2008;23(10):1-8.
3. Katz NP, Adams EF, Chilcoat H, Colucci RD, et al. Challenges in the development of prescription opioid abuse-deterrent formulations. Clin J
Pain. 2007;23:648-660.
4. Substance Abuse and Mental Health Services Administration, Office of Applied Studies. Drug Abuse Warning Network, 2005: National
Estimates of Drug-Related Emergency Department Visits. DAWN Series D-29, DHHS Publication No. (SMA) 07-4256, Rockville, MD, 2007.
Available at http://dawninfo.samhsa.gov/files/DAWN-ED-2005-Web.pdf.
5. Substance Abuse and Mental Health Services Administration. (2008). Results from the 2007 National Survey on Drug Use and Health: National
Findings (Office of Applied Studies, NSDUH Series H-34, DHHS Publication No. SMA 08-4343). Rockville, MD. See
http://oas.samhsa.gov/nsduh/2k7nsduh/2k7Results.pdf.
6. American Pain Foundation. Provider Prescribing Patterns and Perceptions: Identifying Solutions to Build Consensus on Opioid Use in Pain
Management—A Roundtable Discussion. April 2008. Available at www.painfoundation.org.
7. Schumacher MA, Basbaum AI, Way WL. Opioid analgesics & antagonists. In: Katzung, ed. Basic and clinical pharmacology. 10th ed. New
York, NY: McGraw Hill, 2007;489-502.
8. McQuay H. Opioids in pain management. The Lancet. 1999;353:2229-2232.
9. American Pain Foundation. Treatment Options: A Guide for People Living with Pain. 2007. Available at www.painfoundation.org.
10. Furlan AD, Sandoval JA, Mailis-Gagnon AM, Tunks E. Opioids for chronic noncancer pain: a meta-analysis of effectiveness and side effects.
CMAJ. 2006;11:1589-1594.
11. Kuehn BM. Opioid prescriptions soar: increase in legitimate use as well as abuse. JAMA. 2007;297:249-250.
12. Substance Abuse and Mental Health Services Administration. (2007). Results from the 2006 National Survey on Drug Use and Health: National
Findings (Office of Applied Studies, NSDUH Series H-32, DHHS Publication No. SMA 07-4293). Rockville, MD.
13. Bollinger LC, Bush C, Califano JA, et al. Under the counter: the diversion and abuse of controlled prescription drugs in the U.S. The National
Center on Addiction and Substance Abuse at Columbia University (CASA), July 2005.
14. Centers for Disease Control. Unintentional poisoning deaths – United States, 1999-2004. MMWR. February 9, 2007;56(05):93-96.
15. Lin JJ, Afandre D, Moore C. Physician attitudes toward opioid prescribing for patients with persistent noncancer pain. Clin J Pain.
2007;23:799-803.
16. Fine PG, Portenoy RK: Clinical Guide to Opioid Analgesia, 2nd Edition. New York: Vendome, 2007
17. Sinatra R. Opioid analgesics in primary care: challenges and new advances in the management 0f noncancer pain. J Am Board Fam Med.
2006;19:165-77.
18. Boyd C. Presentation at the NIDA/AMA Joint Meeting, Pain, Opioids, and Addiction: An Urgent Problem for Doctors and Patients, NIH,
Bethesda, Maryland, March 5, 2007.

A Reporter’s Guide: Covering Pain and Its Management 33

 “The purpose of life…is to be useful, to be
honorable, to be compassionate, to make some
difference…”
—Ralph Waldo Emerson

34 American Pain Foundation

 Topic Brief
INTEGRATIVE MEDICINE: NON-DRUG TREATMENT OPTIONS
FOR PAIN MANAGEMENT
Pain management continues to challenge when the origin of the pain signals fails to
healthcare providers and places added strain shut off due to damage of the pain alarm
on an already fragmented health care system. system, leaving the person with persisting
The U.S. health system was built around pain.
acute illness; however, because of advances Whatever the cause, chronic pain transcends
in modern medicine and increased longevity, the physical hurting. Persistent pain interferes
many Americans are living longer and with with daily life and relationships, and takes a
one or more chronic conditions (for example, tremendous toll on a person’s mind, body
cancer, diabetes, heart disease and arthritis), and spirit. It’s no surprise that pain and
which require careful coordination of care associated problems (e.g., medication side
and symptom management. effects, depression and anxiety, limited
While pain is a symptom of many chronic mobility) are best managed using a
diseases and is expected after many surgical combination of treatments tailored to each
procedures, persistent pain should not be patient. This is referred to as a “multi-modal”
viewed simply as a symptom. According to or integrative approach.
experts, the pain itself becomes a disease

Multi-modal Therapeutic Strategies for Managing Pain and Related Disability

Pharmacotherapy
(NSAIDs, opioids,
adjuvant analgesics)
Interventional Physical Medicine and
Approaches Rehabilitation
(injections, (assistive devices,
neurostimulation) conditioning)
EFFECTIVE
MANAGEMENT FOR
PERSISTENT PAIN
Complementary and Lifestyle Changes
Alternative Medicine (weight loss, exercise,
(massage, acupuncture) nutrition)
Psychosocial Support
(counseling,
support groups)

Integrative medicine combines conventional medicine with complementary healing

techniques, such as massage, yoga and acupuncture, to address the specific needs. Because an
interdisciplinary approach to pain management is patient-centered, patients learn how to
manage and cope with pain by playing an active role in their treatment plan.

Integrative medicine combines treatments from conventional medicine and complementary and alternative
therapies for which there is some high-quality evidence of safety and effectiveness.1 Being able to deliver
integrated medicine, which incorporates proven CAM therapies into “mainstream” care, is increasingly
important to consumers and healthcare providers.4

A Reporter’s Guide: Covering Pain and Its Management 35

 Benefits of Combined Treatment Patients Seek Complementary
COMMON NON-DRUG OPTIONS
Modalities Treatments
FOR PAIN RELIEF
While medications remain an In their quest for better pain relief,
integral part of pain management patients are increasingly turning to • Stress management techniques
plans, non-drug therapies may be non-drug approaches to help ease (e.g., meditation, deep breathing
used to supplement and enhance their discomfort and give them a and relaxation exercises)
the effectiveness of current pain sense of empowerment and • Massage
medications. These strategies also control. There are a wide variety of • Application of heat or cold,
offer additional options for those non-drug therapies available to including heating pads or
patients at greater risk for, or who treat pain and related disability ice packs
are intolerant of, medication side including: • Acupuncture
effects. • Psychosocial interventions – • Visualization
Moreover, a growing body of cognitive behavioral therapy, • Physical therapy, including
research reinforces the benefits of stress management stretching or exercise
interventions that address the • Rehabilitation techniques – • Hypnotherapy
psychosocial aspects of pain, exercise, heat or cold therapy,
especially given recent evidence • Psychological and spiritual
physical therapy counseling
of a biological link between the • Complementary and alternative
regions of the brain involved with • Biofeedback
medicine – meditation,
depression and pain regulation. acupuncture, hypnotherapy, • Transcutaneous electrical nerve
People with pain often suffer from yoga, aromatherapy, massage, stimulation, also known as TENS
depression, which can affect a touch therapy
patient’s thinking, concentration
Not surprisingly, pain conditions
and behavior, and increase pain
are among those most likely to
sensitivity and severity.
prompt patients to turn to
Effective pain management may complementary and alternative
also require lifestyle changes that medicine (CAM) therapies. These
are supportive of patient mobility practices also give patients a
and independence.2 For example, greater sense of control, so they no
to improve daily functioning, longer feel that they are solely
specific therapies may be dependent on a single pill or
suggested to increase muscle procedure.
strength and flexibility, enhance
sleep and reduce fatigue, and assist
patients in performing usual Diseases/Conditions for Which CAM is Used Most Often
activities and work-related tasks.
16.8%
As with the management of other
chronic illnesses, patients with
chronic pain need to play an active
role in their care and incorporate
non-drug options and other 9.5%
lifestyle changes (e.g., exercise,
proper nutrition) over the long- 6.6%
term. 4.9% 4.9% 4.5%
3.7%
3.1%
2.4% 2.2%

Back pain Head cold Neck pain Joint pain Arthritis Anxiety/ Stomach Headache Recurring Insomnia
depression upset pain

Source: NCCAM, The Uses of CAM in the United States.

36 American Pain Foundation

 INTEGRATIVE MEDICINE: NON-DRUG TREATMENT OPTIONS FOR PAIN MANAGEMENT Topic Brief

What is CAM?
CAM includes a diverse group of healing systems, practices and products that are not part of conventional
medicine. Examples of CAM therapies include acupuncture, massage, meditation, hypnosis, yoga and herbal
therapies. These approaches are increasingly used to help manage pain and related issues (e.g., depression,
anxiety, fatigue) and enhance patients’ quality of life. NCCAM, one of 27 institutes and centers designated by
the National Institutes of Health, is the lead agency for scientific research on CAM and groups these therapies
into four areas.

CAM DOMAINS DEFINED

Mind-body medicine Uses a variety of techniques designed to enhance the mind’s ability to affect the
body’s function and symptoms. Examples include meditation, hypnosis, guided
imagery, prayer, as well as art or music therapy.
Biologically based practices Use substances found in nature, such as herbs, special diets or vitamins. Some
examples include dietary supplements or herbal products (e.g., garlic, ginger, Kava Kava).
Manipulative and Based on manipulation or movement of one or more parts of the body.
body-based practices Examples include massage and chiropractic or osteopathic manipulation.
Energy medicine Involves the use of energy fields, such as magnetic fields or biofields (energy that some
believe surround and run through the body). Examples include qi gong, Reiki and
therapeutic touch.

Many CAM practices are gentle methods that tend to have fewer side effects, which is part of their appeal to
patients. Patients also use these therapies to help alleviate the associated stress, depression and insomnia that
can accompany and worsen pain sensations.
Some CAM practices, such as acupuncture, massage and chiropractic care require the practitioner to be
licensed. It’s important for patients to research and find a CAM practitioner who is certified, willing and
equipped to coordinate with other members of the patient’s health team, and has experience working with
patients with chronic pain.

When tailored to the individual patient, non-drug approaches to

pain management can help:
• Allow patients to take an active role in managing their pain,
thereby, improving patient satisfaction
• Address the physical, emotional and spiritual needs of patients
• Reduce pain and manage related symptoms (e.g., pain and
anxiety, depression, insomnia, fatigue)
• Enhance the effectiveness and minimize adverse effects of
medications
• Reduce health care costs by reducing doctor visits and reliance
on medications
• Improve functioning and the ability to perform activities of
daily living
• Enhance wellness and quality of life

A Reporter’s Guide: Covering Pain and Its Management 37

 More and more Americans are turning to CAM to help manage and treat various health problems,
including pain and distress.

• An estimated 36% of American adults use some form of CAM, and this percentage jumps to 62% if prayer
for health reasons and megavitamin therapy are included.3
• Americans spend at least $34-47 billion on CAM therapies, exceeding out of pocket expenses for all U.S.
hospitalizations. CAM is expected to grow by 15% each year.3
• People report using CAM because these methods mirror their personal beliefs, values and philosophical
orientations toward life.4
• Many people use CAM to help relieve back pain, joint pain, severe headache and pain associated with
migraines, dental and jaw pain and for a variety of other reasons.4

Barriers to Fully Integrating

CAM MOST COMMON CAM THERAPIES
50
Despite CAM’s growing popularity,
43.0
there are barriers to its widespread
use. According to CAM experts, 40
these include:
• Limited scientific evidence about
the safety and effectiveness of 30 24.4

certain therapies. Studies are

18.9
underway to research specific
20 11.6 9.6
CAM practices for pain 7.6
7.5
management. 5.1
5.0 3.5
• Lack of professional training in 10

CAM and integrative medicine Prayer/ Prayer/ Natural Deep Prayer Meditation Chiropractic Yoga Massage Diets
and limited resources to self others products breathing group

coordinate services. 0
Source: Barnes P, Powell-Griner E, McFann K, Nahin R, CDC Advance Data Report
• Restricted health insurance #343, Complemenary and Alternative Medicine Use Among Adults; United States,
2002. May 27, 2004.
coverage. Many CAM therapies
are not yet covered by health
insurance carriers and are,
therefore, only available to
patients on an outpatient fee-for- • Lack of education (on the part • Misperceptions about CAM
service basis. Insurers tend to of consumers and providers) therapies as “elusive,
restrict reimbursement to about the appropriate use of nonsensical options.”
“medically necessary” therapies CAM therapies and how best to Source: American Pain Foundation, Pain
and without the data to back up integrate them with standard Community News, Spring 2008.
their effectiveness, these pain treatments.
practices are not covered.

38 American Pain Foundation

 INTEGRATIVE MEDICINE: NON-DRUG TREATMENT OPTIONS FOR PAIN MANAGEMENT Topic Brief

Paying for non-drug therapies have access to low cost, at-home therapies that
The majority of CAM treatments are not currently provide effective pain relief. These may include heat
covered by traditional insurance plans, largely due to and cold therapies, relaxation techniques and
the absence of scientific evidence proving the exercise.
effectiveness of some CAM therapies. When coverage People living with chronic pain are increasingly
for CAM is offered, it is generally limited to more turning to CAM to help alleviate their suffering and
common therapies such as acupuncture and improve their quality of life. The addition of these
massage. Most people must pay for CAM services therapies often results in better pain relief and fewer
out-of-pocket; however, consumer interest has side effects. However, more research is needed to
prompted more insurance companies to consider prove the effectiveness of certain therapies and
CAM coverage. increase the likelihood that they will be covered by
A study in Washington State, where private health conventional insurance providers and offered as an
insurers are legally required to cover licensed CAM option to all patients living with pain.
providers, found that a significant number of people With nearly half of all consumers concerned about
were utilizing CAM insurance benefits with only a the safety of their health care, 6 the use of CAM and
modest effect on insurance expenditures.5 other non-drug treatments for pain management is
Given the high cost and low insurance coverage of expected to grow as non-drug therapies are proven
many CAM therapies, it is important that patients, safe and effective and adopted into routine health
especially those that are no longer able to work, care.7

For a snapshot of recent research on select CAM therapies,

see the Spring 2008 issue of Pain Community News at www.painfoundation.org.

REFERENCES
1. What is CAM? Retrieved October 10, 2008 from National Center for
Complementary and Alternative Medicine (NCCAM). Web site:
http://nccam.nih.gov/health/whatiscam/
2. Ahmad, M, Goucke, C.R. (2002) Management strategies for the treatment of
neuropathic pain in the elderly. Drugs Aging, 19(12):929-4.
3. Barnes, P., Powell-Griner, E., McFann, K., Nahin, R. CDC Advance Data Report
#343. Complementary and Alternative Medicine Use Among Adults: United States,
2002. May 27, 2004.
WEB RESOURCES
4. Treatment Options: A Guide for People Living with Pain. Retrieved October 10,
2008 from American Pain Foundation. American Academy of Pain Management
Web site: http://www.painfoundation.org/Publications/TreatmentOptions2006.pdf www.aapainmanage.org
5. Lafferty, W.E., Tyree, P.T., et al. (2006) Insurance Coverage and Subsequent American Pain Foundation Treatment Options
Utilization of Complementary and Alternative Medical (CAM) Providers. Am J www.painfoundation.org/Publications/
Manag Care, 12(7):397–404. TreatmentOptions2006.pdf
6. Henry J. Kaiser Family Foundation (November 17, 2004). “Five years after IOM
National Center for Complementary and
report on medical errors, nearly half of all consumers worry about the safety of
Alternative Medicine (NCCAM)
their health care” Press release. Retrieved October 12, 2008 from
www.nccam.nih.gov
http://www.kff.org/kaiserpolls/pomr111704nr.cfm
7. The Pain Community News: Spring 2008, 8(2). Retrieved October 10, 2008 from The Office of Cancer Complementary and
American Pain Foundation. Web site: Alternative Medicine
http://www.painfoundation.org/Publications/PCN08spring.pdf www.cancer.gov/cam

A Reporter’s Guide: Covering Pain and Its Management 39

Pain A to Z
Common Pain Terms and Syndromes
Hundreds of pain syndromes or disorders make up the spectrum of pain.There are the most
benign, fleeting sensations of pain, such as a pin prick.There is the pain of childbirth, the pain of
a heart attack, and the pain that sometimes follows amputation of a limb.There is also pain
accompanying cancer and the pain that follows severe trauma, such as that associated with head
and spinal cord injuries.A sampling of common pain terms and syndromes follows, listed
alphabetically.

Acute Pain occurs suddenly due to illness, injury or surgery. It Breakthrough Pain is intermittent worsening of pain that occurs
has a short duration that subsides when the injured tissue heals. spontaneously or in relation to a specific activity. The pain
increases above the level of pain being treated with ongoing
Arachnoiditis is a condition in which one of the three analgesics (pain medications).
membranes covering the brain and spinal cord, called the
arachnoid membrane, becomes inflamed. A number of causes, Burn pain can be profound and poses an extreme challenge to
including infection or trauma, can result in inflammation of this the medical community. First-degree burns are the least severe;
membrane. Arachnoiditis can produce disabling, progressive, and with third-degree burns, the skin is lost. Depending on the injury,
even permanent pain. pain accompanying burns can be excruciating, and even after the
wound has healed patients may have chronic pain at the burn
Arthritis is the most prevalent cause of chronic disability in the site.
United States. Millions of Americans suffer from arthritic
conditions such as osteoarthritis, rheumatoid arthritis, ankylosing Cancer pain can accompany the growth of a tumor, the
spondylitis, and gout. These disorders are characterized by joint treatment of cancer, or chronic problems related to cancer’s
pain in the extremities. Many other inflammatory diseases affect permanent effects on the body. Fortunately, most cancer pain can
the body’s soft tissues, including tendonitis and bursitis. be treated to help minimize discomfort and stress to the patient.

Back pain has become the high price paid by our modern Central pain syndrome — see Traumatic Pain below.
lifestyle and is a startlingly common cause of disability for many
Americans, including both active and inactive people. Common Chronic Pain is pain that persists for long periods of time
types of back pain include: (usually >3 months). Failure to treat acute pain promptly and
appropriately at the time of injury, during initial medical and
• Sciatica — back pain that spreads to the leg (see below). surgical care, and at the time of transition to community-based
care, contributes to the development of chronic pain syndromes.
• Degenerative or ruptured disc — type of back pain
In chronic pain, pain signals may remain active in the nervous
associated with the discs of the spine, the soft, spongy
system for weeks, months or even years. Chronic pain has no
padding between the vertebrae (bones) that form the spine.
value or benefit; it is a disease of the nervous system.
Discs protect the spine by absorbing shock, but they tend to
degenerate over time and may sometimes rupture. Types of Chronic Pain:
• Spondylolisthesis — back condition that occurs when one • Intermittent Pain - episodic and may occur in waves or
vertebra extends over another, causing pressure on nerves patterns.
and therefore pain.
• Persistent Pain - lasts 12 or more hours every day for more
• Radiculopathy — damage to nerve roots is a serious than three months.
condition that can be extremely painful.
Complex Regional Pain Syndrome, or CRPS, is a chronic pain
Treatment for a damaged disc includes drugs such as condition that typically affects one or more limbs. It is
painkillers, muscle relaxants, and steroids; exercise or rest, accompanied by burning pain and hypersensitivity to
depending on the patient’s condition; adequate support, such temperature. Often triggered by trauma or nerve damage, CRPS
as a brace or better mattress and physical therapy. In some causes the skin of the affected area to become characteristically
cases, surgery may be required to remove the damaged shiny.
portion of the disc and return it to its previous condition, There are two types of CRPS:
especially when it is pressing a nerve root. Surgical procedures
include discectomy, laminectomy, or spinal fusion. Minimally • CRPS I (formerly known as Reflex Sympathetic Dystrophy
invasive procedures (vertebroplasty), certain complementary Syndrome, or RSDS) is frequently triggered by tissue injury,
and alternative therapies and implantable devices may also but with no underlying or identifiable nerve injury.
help certain patients.

40 American Pain Foundation

 • CRPS II (formerly known as Causalgia) is characterized individual. It can result from diseases that affect nerves (such as
by the same symptoms, but these cases are clearly associated diabetes) or from trauma, or, because chemotherapy drugs can
with a specific nerve injury. affect nerves, it can be a consequence of cancer treatment.
Among the many neuropathic pain conditions are:
The cause of CRPS is not well understood, but experts believe
it is due to a malfunction of the autonomic nervous system • Diabetic neuropathy, which results from nerve damage
following blunt trauma to an arm or leg, after surgical secondary to vascular problems that occur with diabetes;
procedures or even from minor injuries such as a sprain or
• Reflex sympathetic dystrophy syndrome (see below),
fracture. Nerves begin to misfire, repeatedly sending pain
which can follow injury;
impulses to the brain. The resulting pain seems out of
proportion to the severity of the injury. • Phantom limb and post-amputation pain, which can
result from the surgical removal of a limb;
Deafferentation Pain: pain due to alteration or damage to the
• Postherpetic neuralgia, which can occur after an outbreak
central nervous system (central pain or neuropathic pain) or may
of shingles; and
be alteration of nervous system within larger nerves or nerve
roots before entry into central nervous system. • Central pain syndrome, which can result from trauma to
the brain or spinal cord.
Fibromyalgia is a chronic pain disorder characterized by
widespread musculoskeletal pain that has lasted for at least three Nociceptive pain - caused by an injury that stimulates pain
months. People with fibromyalgia report general tenderness and receptors. Pain receptors, located on the tips of nerve cells,
soreness, muscle stiffness, especially in the morning, as well as recognize and react to an unpleasant stimulus (pressure, extreme
fatigue. Stress or lack of sleep can make the symptoms of temperatures [hot or cold], substances released by other cells) and
fibromyalgia worse. An estimated 6 million Americans have send pain signals through the nervous system for recognition and
fibromyalgia, most of them women. response. This type of pain may be accompanied by
inflammation. Infections, burns, cuts, a severe lack of oxygen in
Headaches affect millions of Americans. The three most common the blood, and stretching of or pressure within an organ, can
types of chronic headache are migraines, cluster headaches, and injure tissues and cause nociceptive pain.
tension headaches. Each comes with its own telltale brand of
pain. Types of Nociceptive Pain:

• Migraines are characterized by throbbing pain and • Somatic Pain - caused by injury to skin, muscles, bone,
sometimes by other symptoms, such as nausea and visual joint, and connective tissues. Deep somatic pain is usually
disturbances. Migraines are more frequent in women than described as dull or aching, and localized in one area.
men. Stress can trigger a migraine headache, and migraines Somatic pain from injury to the skin or the tissues just below
can also put the sufferer at risk for stroke. it often is sharper and may have a burning or pricking
quality.
• Cluster headaches are characterized by excruciating,
piercing pain on one side of the head; they occur more • Visceral Pain - originates from ongoing injury to the internal
frequently in men than women. organs or the tissues that support them. When the injured
tissue is a hollow structure, like the intestine or the gall
• Tension headaches are often described as a tight band bladder, the pain often is poorly localized and feels like
around the head. cramping. When the injured structure is not a hollow organ,
the pain may be pressure-like, deep, and stabbing.
Head and facial pain can be agonizing, whether it results from
dental problems or from disorders such as cranial neuralgia, in Pain flares. Pain that suddenly erupts or emerges with or
which one of the nerves in the face, head, or neck is inflamed. without an aggravating event or activity.
Another condition, trigeminal neuralgia (also called tic
douloureux), affects the largest of the cranial nerves and is Peripheral Neuropathic Pain due to vascular disease or injury-
characterized by a stabbing, shooting pain. such as vasculitis or inflammation of blood vessels, coronary
artery disease, and circulatory problems-all have the potential to
Muscle pain can range from an aching muscle, spasm, or strain, cause pain. Vascular pain affects millions of Americans and occurs
to the severe spasticity that accompanies paralysis. Another when communication between blood vessels and nerves is
disabling syndrome is fibromyalgia, a disorder characterized by interrupted. Ruptures, spasms, constriction, or obstruction of
fatigue, stiffness, joint tenderness, and widespread muscle pain. blood vessels, as well as a condition called ischemia in which
Polymyositis, dermatomyositis, and inclusion body myositis blood supply to organs, tissues, or limbs is cut off, can also result
are painful disorders characterized by muscle inflammation. They in pain.
may be caused by infection or autoimmune dysfunction and are
sometimes associated with connective tissue disorders, such as Reflex sympathetic dystrophy syndrome — see Complex
lupus and rheumatoid arthritis. Regional Pain Syndrome.

Myofascial pain syndromes affect sensitive areas known as Repetitive stress injuries are muscular conditions that result
trigger points, located within the body’s muscles. Myofascial pain from repeated motions performed in the course of normal work
syndromes are sometimes misdiagnosed and can be debilitating. or other daily activities. They include:

Neuropathic Pain – is a type of pain that results from damage to • writer’s cramp, which affects musicians and writers and
or dysfunction of the nerves in either the peripheral or central others,
nervous system, rather than stimulation of pain receptors (as is • compression or entrapment neuropathies, including carpal
the case of somatic and visceral pain). Neuropathic pain can tunnel syndrome, caused by chronic overextension of the
occur in any part of the body and is frequently described as a wrist and
hot, burning sensation, which can be devastating to the affected
• tendonitis or tenosynovitis, affecting one or more tendons.

A Reporter’s Guide: Covering Pain and Its Management 41

Sciatica is a painful condition caused by pressure on the sciatic Surgical pain may require regional or general anesthesia during
nerve, the main nerve that branches off the spinal cord and the procedure and medications to control discomfort following
continues down into the thighs, legs, ankles, and feet. Sciatica is the operation. Control of pain associated with surgery includes
characterized by pain in the buttocks and can be caused by a presurgical preparation and careful monitoring of the patient
number of factors. Exertion, obesity, and poor posture can all cause during and after the procedure.
pressure on the sciatic nerve. One common cause of sciatica is a
herniated disc. Temporomandibular disorders are conditions in which the
temporomandibular joint (the jaw) is damaged and/or the muscles
Shingles and other painful disorders affect the skin. Pain is a used for chewing and talking become stressed, causing pain. The
common symptom of many skin disorders, even the most condition may be the result of a number of factors, such as an
common rashes. One of the most vexing neurological disorders is injury to the jaw or joint misalignment, and may give rise to a
shingles or herpes zoster, an infection that often causes agonizing variety of symptoms, most commonly pain in the jaw, face,
pain resistant to treatment. Prompt treatment with antiviral agents and/or neck muscles. Physicians reach a diagnosis by listening to
is important to arrest the infection, which if prolonged can result the patient’s description of the symptoms and by performing a
in an associated condition known as postherpetic neuralgia. simple examination of the facial muscles and the
Other painful disorders affecting the skin include: temporomandibular joint.

• Vasculitis, or inflammation of blood vessels; Traumatic pain can occur after injuries in the home, at the
workplace, during sports activities, or on the road. Any of these
• Other infections, including herpes simplex;
injuries can result in severe disability and pain. Some patients
• Skin tumors and cysts, and who have had an injury to the spinal cord experience intense
Tumors associated with neurofibromatosis, a neurogenetic pain ranging from tingling to burning and, commonly, both. Such
disorder. patients are sensitive to hot and cold temperatures and touch. For
these individuals, a touch can be perceived as intense burning,
Somatic pain—see Nociceptive Pain. indicating abnormal signals relayed to and from the brain. This
condition is called central pain syndrome or, if the damage is
Sports injuries are common. Sprains, strains, bruises, in the thalamus (the brain’s center for processing bodily
dislocations, and fractures are all well-known words in the sensations), thalamic pain syndrome. It affects as many as
language of sports. Pain is another. In extreme cases, sports 100,000 Americans with multiple sclerosis, Parkinson’s disease,
injuries can take the form of costly and painful spinal cord and amputated limbs, spinal cord injuries, and stroke. Their pain is
head injuries, which cause severe suffering and disability. severe and is extremely difficult to treat effectively. A variety
Spinal stenosis refers to a narrowing of the canal surrounding of medications, including analgesics, antidepressants,
the spinal cord. The condition occurs naturally with aging. Spinal anticonvulsants, and electrical stimulation, are options available
stenosis causes weakness in the legs and leg pain usually felt to central pain patients.
while the person is standing up and often relieved by sitting Visceral pain – see Nociceptive Pain.
down.

Sources:

American Pain Foundation. Treatment Options: A Guide for People

Living with Pain. Available at www.painfoundation.org.

“Pain: Hope Through Research,” National Institutes of Neurological

Disorders and Stroke. Publication date December 2001. NIH
Publication No. 01-2406 . Last updated July 31, 2008.

42 American Pain Foundation

 Pain Resources

American Pain Foundation

888-615-7246
www.painfoundation.org

Key Publications Special Projects/Initiatives

• Pain Community News, APF’s quarterly newsletter • APF’s grassroots Power Over Pain Action Network
• Pain Monitor, APF’s monthly e-news update (POPAN) has 72 POPAN leaders in 36 states tirelessly
• Treatment Options: A Guide for People Living with working to help improve pain care, legislation
Pain related to pain care, healthcare access and medical
practices.
• Pain Resource Guide: Getting the Help You Need
• Military and Veterans Pain Initiative
• Targeting Chronic Pain Notebook and companion
provider resources • Spotlight Series on cancer pain, fibromyalgia and
shingles
• APF Report, Provider Prescribing Patterns and
Perceptions: Identifying Solutions to Build Consensus • Pain & Creativity
on Opioid Use in Pain Management • Yoga for Chronic Pain
• Fact sheets on cancer pain, shingles/PHN, • Let’s Talk Pain Coalition, www.letstalkpain.org,
fibromyalgia, military/veterans and pain, among launched in partnership with the American Academy
others of Pain Management and the American Society for
• Top 10 Tips Series, including: Pain Management Nursing
• Finding Quality Health Information Online
• Exercising for Pain Relief
• Making the Most of Your Medical Visits
For more information about APF’s programs and services,
• Easing Pain Around the Holidays see the 2007 Annual Report at
• Pain-free Tips for Travelers http://www.painfoundation.org/About/2007AnnualReport.pdf
• Helpful Hints on the Road to Pain Relief
• Pain Care Bill of Rights

To subscribe to print or online publications, please visit www.painfoundation.org,

or call Tina Register, Communications Manager,
at (443) 690-4707 or [email protected]

A Reporter’s Guide: Covering Pain and Its Management 43

Other Consumer Pain Associations Other organizations
American Chronic Pain Association Pain Policy Studies
800-533-3231
www.theacpa.org Pain and Policy Studies Group (PPSG)
National Pain Foundation 608-263-7662
303-783-8899 www.painpolicy.wisc.edu
www.nationalpainfoundation.org
Pain Law Studies

Pain and the Law

Condition-Specific Pain Organizations 617-262-4990
The American Pain Foundation keeps an updated and www.painandthelaw.org
searchable listing of condition-specific patient advocacy and
professional organizations at www.painfoundation.org. These The Legal Side of Pain
include such groups as the Amputee Coalition of America, 865-560-1945
Arthritis Foundation, the National Vulvodynia Association, www.legalsideofpain.com
National Fibromyalgia Association and the American Diabetes
Association, among others. National Association of Attorneys General
www.naag.org

Professional Pain Associations Drug Abuse/Addiction Groups

Alliance of State Pain Initiatives National Institute on Drug Abuse
608-262-0978 301-443-1124
E-mail: [email protected] www.nida.nih.gov
American Academy Hospice and Palliative Medicine Drug Enforcement Administration
847-375-4712 Office of Diversion Control
www.aahpm.org 800-882-9539
www.deadiversion.usdoj.gov
American Academy of Pain Management
209-533-9744 Partnership for a Drug-Free America
www.aapainmanage.org 212-922-1560
http://drugfreeamerica.com
American Academy of Pain Medicine
847-375-4731 Substance Abuse and Mental Health Services
www.painmed.org Administration (SAMHSA)
877-726-4727
American Pain Society www.samhsa.gov
847-375-4715
www.ampainsoc.org White House Office of National
Drug Control Policy
American Society of Addiction Medicine 800-666-3332
301-656-3920 www.whitehousedrugpolicy.gov
www.asam.org
Others
American Society for Pain Management Nursing
913-895-4606 Center for Practical Bioethics
www.aspmn.org 800-344-3829
www.practicalbioethics.org
National Hospice & Palliative Care Organization
703-837-1500 Federation of State Medical Boards (FSMB)
www.nhpco.org 817-868-4000
www.fsmb.org

National Family Caregivers Association

301-942-6430
www.nfcacares.org

44 American Pain Foundation

“Pain is inevitable. Suffering is optional.”
— Anonymous
 201 N. Charles St., Suite 710 • Baltimore, MD 21201-4111 • 1-888-615-PAIN (7246)
[email protected] • www.painfoundation.org

The American Pain Foundation is solely responsible for the content and maintains editorial control of all materials and publications we produce.
We gratefully acknowledge those who support our work. This publication was underwritten by support from Alpharma Pharmaceuticals LLC.
Publication date: October 2008
  
 
EXHIBIT F 
 bs_bs_banner

Pain Medicine 2014; 15: 1911–1929

Wiley Periodicals, Inc.

Risk Factors for Serious Prescription

Opioid-Related Toxicity or Overdose among
Veterans Health Administration Patients

Barbara Zedler, MD,* Lin Xie, MS,† Li Wang, PhD,† Design. Retrospective, nested, case-control ana-
Andrew Joyce, PhD,* Catherine Vick, MS,* lysis of Veterans Health Administration (VHA)
Furaha Kariburyo, MPH,† Pradeep Rajan, ScD,* medical, pharmacy, and health care resource utiliza-
Onur Baser, PhD,† and Lenn Murrelle, PhD, MSPH* tion administrative data.

*Venebio Group, Richmond, Virginia; †STATinMED Subjects. Patients dispensed an opioid by VHA
Research, Dallas, Texas, USA between October 1, 2010 and September 30, 2012
(N = 8,987).
Reprint requests to: Barbara K. Zedler, MD, Venebio
Group, LLC, 7400 Beaufont Springs Drive, Methods. Cases (N = 817) experienced life-
Suite 300, Richmond, VA 23225, USA. threatening opioid-related respiratory/CNS depres-
Tel: 877-344-4347, ext. 507; Fax: 804-272-3497; sion or overdose. Ten controls were randomly
E-mail: [email protected]. assigned to each case (N = 8,170). Logistic regres-
sion was used to examine associations with the
Disclosure: This research was funded by kaléo, Inc. outcome.
The study was conceived, designed, executed, and
reported by the authors who had sole control over the Results. The strongest associations were maxi-
data and the decision to publish. Kaléo, Inc. reviewed mum prescribed daily morphine equivalent dose
and commented on the methods developed by the (MED) ≥ 100 mg (odds ratio [OR] = 4.1, 95% con-
authors and reviewed the final manuscript for fidence interval [CI], 2.6–6.5), history of opioid
proprietary information. Drs. Murrelle, Zedler, Joyce, dependence (OR = 3.9, 95% CI, 2.6–5.8), and hospi-
and Rajan are Principals of Venebio Group, LLC, talization during the 6 months before the serious
which has research and consulting agreements with toxicity or overdose event (OR = 2.9, 95% CI,
kaléo, Inc. and Reckitt-Benckiser Pharmaceuticals, 2.3–3.6). Liver disease, extended-release or long-
Inc. and reports no additional conflicts of interest. acting opioids, and daily MED of 20 mg or more were
The other coauthors report no conflicts of also significantly associated.
interest.
Conclusions. Substantial risk for serious opioid-
related toxicity and overdose exists at even relatively
low maximum prescribed daily MED, especially in
Abstract patients already vulnerable due to underlying demo-
graphic factors, comorbid conditions, and concomi-
Objective. Prescription opioid use and deaths tant use of CNS depressant medications or
related to serious toxicity, including overdose, have substances. Screening patients for risk, providing
increased dramatically in the United States since education, and coprescribing naloxone for those at
1999. However, factors associated with serious elevated risk may be effective at reducing serious
opioid-related respiratory or central nervous system opioid-related respiratory/CNS depression and over-
(CNS) depression or overdose in medical users are dose in medical users of prescription opioids.
not well characterized. The objective of this study
was to examine the factors associated with serious Key Words. Prescription; Opioid; Toxicity;
toxicity in medical users of prescription opioids. Overdose; Risk; Predictors

1911

Downloaded from https://academic.oup.com/painmedicine/article-abstract/15/11/1911/1835923

by guest
on 26 January 2018
 Zedler et al.

Introduction of substance abuse, previous overdose, mental illness,

and respiratory disease are significantly more likely to die
Serious toxicity, including overdose, related to prescription of an opioid-related overdose [7,16,20,21,25,26]. Pre-
opioid analgesics has increased dramatically in the United scription drug-related factors significantly associated with
States since 1999 [1,2]. Opioids are central nervous fatal opioid-related overdose or serious toxicity include
system (CNS) depressants. Life-threatening opioid toxicity use of oxycodone, methadone, and extended-release for-
includes profound sedation/coma and severe respiratory mulations [7,12,16,18,27–29]; maximum prescribed daily
depression that can result in death from respiratory arrest MED exceeding 50 mg [21,25]; and concurrent use of
[3–5]. Prescription drug “overdose” is a type of serious other psychoactive CNS depressants (e.g., sedative–
toxicity in which the drug is used in amounts that exceed hypnotics, anxiolytics, alcohol) [1,20,26,30].
the individual’s ability to tolerate the exposure, result-
ing in serious adverse effects. Serious opioid-related To date, most research on predictors of serious opioid-
respiratory/CNS depression can occur unintentionally in related toxicity or overdose has focused on fatal events,
patients using them for approved therapeutic indications illicit opioids, nonmedical users of prescription opioids, or
(“medical users”) and even at dosages in the recom- limited samples of medical users and used relatively small,
mended prescribing range. Medical users taking opioids geographically limited convenience samples. The objec-
as prescribed may experience circumstances that predis- tive of this study was to identify the factors independently
pose them to opioid accumulation, prolonged duration of most associated with overdose or life-threatening
action or enhanced CNS, and consequent respiratory respiratory/CNS depression, including nonfatal events,
depression. Examples include certain comorbid condi- among medical users of prescription opioids in a large,
tions (e.g., impaired renal, hepatic, or respiratory function) national, administrative health care database.
and concomitant medications or substances (e.g., seda-
tives, alcohol). Opioid pain relievers were involved in nearly Methods
17,000 deaths in 2010, representing a threefold increase
since 1999 and three-fourths of all prescription drug Study Design
poisoning deaths [1,2]. The alarming upward trajectory of
fatal unintentional overdoses parallels increases of A nested case-control design was used to examine
29–80% in the use of prescription opioids for long-term factors associated with a diagnosis of serious opioid-
management of chronic noncancer pain (2000–2005) in related respiratory/CNS depression or overdose among
an estimated 9 million US adults per year currently [6–11]. Veterans Health Administration (VHA) patients who were
Approximately 60% of overdoses occur in medical users dispensed an opioid by VHA. The study was exempt from
of maximum prescribed daily morphine equivalent doses Institutional Review Board review.
(MED) of 100 mg or more1 or those who misuse opioid
analgesics, typically prescribed by a single physician, to
manage chronic pain [7]. The remaining 40% of overdoses Study Setting and Data Source
occur in nonmedical users who abuse prescription opioids
for recreational purposes, tend to receive prescriptions A retrospective analysis of deidentified national adminis-
from multiple prescribers, and engage in diversion of pre- trative health care data was conducted using VHA Medical
scription opioids to and from others [7,12,13]. SAS datasets from October 1, 2010 through September
30, 2012. These datasets contain data for VHA-provided
The factors associated with fatal opioid-related overdose health care that is utilized primarily by US military veterans
have been well characterized [2,7,12,14–21]. Patient- and a small number of nonveterans (e.g., employees,
related factors include certain demographic charac- eligible family members, research participants) and include
teristics and clinical comorbidities. Men have a higher inpatient, outpatient, laboratory, radiology, pharmacy, vital
opioid-related overdose death rate [12], but the percent- signs, vital status, and enrollment information.
age rise in deaths since 1999 is greater in women [15]. For
prescription opioids, overdose death rates are highest in Study Sample
persons aged 45–54 years; non-Hispanic whites, Ameri-
can Indians and Alaskan Natives; rural and impoverished Study “cases” were defined as patients who satisfied the
areas; and in the West and Southwest United States and following criteria at any time between October 1, 2010
the Appalachian states of Kentucky and West Virginia and September 30, 2012 (the “study period”): 1) were
where the opioid analgesic prescribing rates are highest dispensed at least one opioid prescription by VHA (see
[2,8,12,18,19,22,23]. Geographic variations in overdose Appendix I), identified by national drug code; and 2) had a
deaths reflect, in part, variations in opioid analgesic pre- claim for a serious opioid-related toxicity or overdose
scribing patterns, the number of physicians available, and event based on International Classification of Disease, 9th
state-regulated pain management policies rather than Revision, Clinical Modification (ICD-9-CM) codes and
inherent patient differences [2,24]. Persons with a history Current Procedure Terminology (CPT) codes (Table 1)
[7,21,31]. A serious opioid-related toxicity or overdose
1 event was defined as follows: 1) a listed CNS or respira-
Maximum prescribed daily morphine equivalent doses tory adverse effect code in addition to a listed poisoning
exceeding 200 mg are considered ’high-dose.’ [55] event or external cause code occurring within ±1 day of

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Table 1 Diagnostic codes for serious opioid-related toxicity including overdose

ICD-9-CM Diagnosis
Codes Description

Poisoning codes
965.00 Poisoning by opium (alkaloids), unspecified
965.01 Poisoning by heroin
965.02 Poisoning by methadone
965.09 Poisoning by other opiates and related narcotic
Adverse effect codes
518.81 Acute respiratory failure
518.82 Other pulmonary insufficiency, not elsewhere classified
780.0 Alteration of consciousness
786.03 Apnea
799.0 Asphyxia and hypoxemia
CPT codes for mechanical ventilation or critical care
31500 Intubation, endotracheal, emergency procedure
94002 Ventilation assist and management, initiation of pressure, or volume preset ventilators for assisted
or controlled breathing; hospital inpatient/observation, each subsequent day
94660 CPAP ventilation; initiation and management
94662 CNAP ventilation; initiation and management
99291 Critical care, evaluation, and management of the critically ill or critically injured patient, first 30–74
minutes
External cause codes
E850.0 Accidental poisoning by heroin
E850.1 Accidental poisoning by methadone
E850.2 Accidental poisoning by other opiates and related narcotics
E935.0 Adverse effects of heroin
E935.1 Adverse effects of methadone
E935.2 Adverse effects of other opioids and related narcotics

CNAP = continuous negative airway pressure; CPAP = continuous positive airway pressure; ICD-9-CM, International Classification
of Disease, 9th Revision, Clinical Modification.

the adverse effect; or 2) use of mechanical ventilation or Baseline Variables

critical care in addition to a listed poisoning event or
external cause code occurring within ±1 day of the critical Baseline demographic variables included age group (18–
respiratory support. The first identified occurrence 34, 35–44, 45–54, 55–64, 65+ years), sex, race, marital
of opioid-related overdose or life-threatening respiratory/ status, body mass index, and the US Census region of the
CNS depression (“index event”) during the study period patient’s VHA treatment center (Northeast, North Central,
served as the “index date” for cases. All patients were South, West, other). Baseline comorbidity measures
required to have nonmissing age, sex, and race values in included the Charlson Comorbidity Index score, calcu-
addition to continuous medical and pharmacy benefits in lated as the sum of assigned comorbidity category
the 6 months before the index date (the “baseline period”). weights [32].
For cases, the follow-up period was calculated as the
number of days after the end of the event until death, Other selected baseline comorbidities were stratified as
disenrollment, or the end of the study period. pain-related and nonpain-related [33–36]. Pain-related
comorbid conditions included low back disorders, other
For each case, 10 control patients were randomly back/neck disorders, neuropathic disorders, fibromyalgia,
selected and assigned from those who 1) were dis- headache/migraine, burns, traumatic injury, and motor
pensed an opioid by VHA during the study period; 2) did vehicle accidents. Nonpain-related comorbidities included
not experience serious opioid-related toxicity or over- psychoactive substance use disorders including sub-
dose as defined in the study; and 3) had complete data stance abuse and nonopioid substance dependence,
for age, sex, and race. The case index date was tobacco use disorder, post-traumatic stress disorder,
assigned to each of the 10 control patients, and the bipolar disorder, attention deficit hyperactivity disorder,
follow-up period for these controls was the number of schizophrenia, anxiety disorder, obsessive-compulsive–
days thereafter until death, disenrollment, or the end of disorder, cardiovascular disease, endocarditis, viral and
the study period. alcoholic hepatitis), pancreatitis, sexually transmitted

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disease, herpes simplex infection, skin infections/ Table 2 Prescription opioids and morphine
abscesses, sleep apnea, and obesity. equivalent conversion factors
Additional baseline variables included the number of
Morphine
opioid prescriptions dispensed by VHA, opioid used
Equivalent
(categorized by active ingredient, formulation [extended-
Conversion
release/long-acting vs short-acting], and route [oral, par-
Factor†,‡ (per
enteral, transdermal, other]), and the maximum prescribed
Opioid* mg of Opioid)
daily MED. For each opioid prescription dispensed during
the baseline period, the product of the number of units Short acting
dispensed and the opioid strength per unit (milligrams) Meperidine hydrochloride 0.1
was divided by the number of days supplied. The resulting Codeine 0.15
opioid daily dose dispensed (milligrams per day) was then Tramadol 0.2
multiplied by a conversion factor derived from published Hydrocodone 1.0
sources to estimate the daily dose in morphine equivalents Morphine sulfate 1.0
(MED) (see Table 2) [37–42]. The maximum prescribed Oxycodone 1.5
daily MED during the baseline period was calculated for Oxymorphone 3.0
each patient by summing the daily MED for all opioid Hydromorphone 4.0
prescriptions dispensed to the patient during those 6 Fentanyl citrate (transmucosal) 0.13§
months. It reflects the maximum prescribed daily dose Extended release/long-acting
and not necessarily the actual amount consumed. Morphine sulfate extended-release 1.0
Nonopioid medications also dispensed by VHA which can Oxycodone hydrochloride 1.5
potentiate opioid-associated serious adverse effects, controlled-release
such as psychoactive drugs and nonopioid analgesics, Methadone 3.0
were included as baseline variables [1,28]. Baseline health Fentanyl (transdermal) 2.4¶, **
care utilization measures included the number of inpatient
admissions and outpatient emergency department (ED), * Some drug products contained an opioid in combination with
office, and pharmacy visits (Table 6). a nonopioid (e.g., acetaminophen, aspirin) (Appendix II). No
MED was calculated for the two controls who used sublingual
Outcome Variable buprenorphine.
†
Sources of morphine equivalent conversion factors: Von Korff
The occurrence of serious opioid-related toxicity or over- [37] and Leppert and Luczak [69].
‡
dose as defined by listed ICD-9-CM and CPT codes was For each opioid dispensed, the daily MED (mg per day) was
the primary outcome variable (Table 1). All analyses were calculated as follows (see text): (number of units dis-
conducted at the patient level. For patients who experi- pensed × strength of unit [mg] × MED conversion factor)/
enced more than one episode of serious opioid-related number of days supply.
§
Converting transmucosal fentanyl to morphine equivalents
respiratory/CNS depression or overdose during the study
assumes 50% bioavailability of transmucosal fentanyl and that
period, only the index event was evaluated.
100 μg of transmucosal fentanyl is equivalent to 12.5–15 mg of
morphine.
Statistical Analysis ¶
Converting transdermal fentanyl to morphine equivalents
assumes that each patch has a conversion factor of 2.4 and
Baseline covariates and the outcome measure were sum- remains in place for 3 days. The daily MED (mg per day) was
marized descriptively. Tests for normality were conducted, calculated as follows:
and medians and interquartile ranges (IQRs) were calcu- (number of patches dispensed × 3 days per patch × strength of
lated for continuous variables that were not normally dis- patch [μg/h] × MED conversion factor)/number of days supply.
tributed. Frequencies and percentages were calculated ** Prescription Drug Monitoring Program Training and Techni-
for categorical variables. Student’s t-tests or Wilcoxon cal Assistance Center (no specific author) [41].
Rank Sum tests were used, as appropriate, to examine MED = morphine equivalent dose.
differences in continuous variables of interest between
cases and controls. Chi-squared tests of proportion were care resource utilization. Odds ratios (ORs) and corre-
used to examine bivariate associations for categorical sponding 95% confidence intervals (CIs) and P values
variables. were calculated. P values less than 0.05 were considered
statistically significant. One full, main effects, logistic
Multivariable analysis was performed using conditional regression model was run. Model discrimination was
logistic regression to examine factors potentially associ- evaluated by the c-statistic which reflects the area under
ated with the index event of serious opioid-related toxicity the receiver operating characteristic curve and ranges
or overdose. The covariates included in the regression from 0.5 (no discrimination between cases and controls)
model were age, sex, race/ethnicity, marital status, US to 1.0 (perfect discrimination) [41]. [43] Only the first
Census region, comorbidities, prescription opioid charac- (index) event of serious opioid-related toxicity or overdose
teristics, the maximum prescribed daily MED, selected was modeled for case patients who experienced more
nonopioid prescription medications, and baseline health than one episode during the study period.

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 Risk Factors Prescription Opioid Toxicity Overdose

All analyses were conducted using SAS version 9.3 asthma, pneumoconiosis, asbestosis); depression; skin
[44]. ulcers; hypertension; malignancy; opioid dependence,
substance abuse, nonopioid substance dependence, and
Results tobacco use disorder; viral hepatitis; mental health disor-
ders including anxiety, post traumatic stress, and bipolar
Sixteen patients were excluded from the analysis due to disorders; cardiovascular disease; sleep apnea; back and
missing age, sex, or race data. We identified 921 patients neck disorders; neuropathic disorders; and traumatic injury
with a claim of life-threatening opioid-related respiratory/ (e.g., fracture, dislocation, contusion, laceration, wound).
CNS depression or overdose and at least 6 months of
continuous medical and pharmacy benefits before the VHA prescription drug dispensing data during the
event, 817 of whom were also dispensed an opioid by 6-month baseline period indicated that, overall, cases
VHA. Among these 817 cases, 16 experienced more than were prescribed opioids significantly more often than
one episode during the study period. Among those who controls, in larger variety, with a higher proportion of
received an opioid prescription from VHA during the study extended-release or long-acting (ER/LA) formulations
period, 8,170 control patients without overdose were and with a higher mean maximum prescribed daily MED
identified who met selection criteria (Figure 1). (Table 5). The mean number of opioid prescriptions dis-
pensed in the baseline period was 6.8 among cases,
Descriptive Analysis compared with 2.5 among controls (P < 0.0001). Pre-
scription opioid active ingredients varied significantly
The median age was 62 years for both cases and controls between cases and controls, with more hydroco-
(IQR, 10 and 16, respectively). As shown in Table 3, cases done, methadone, oxycodone, and morphine, but less
were more likely than controls to be non-Hispanic white, tramadol, dispensed to cases than controls. Both ER/LA
divorced, separated or widowed, and to reside in the and short-acting formulations as well as oral opioids
western US Census region. were prescribed to cases more often than to controls.
The mean maximum prescribed MED was 122 mg per
Compared with controls, patients with serious opioid- day in cases and 48 mg per day in controls, with sig-
related toxicity or overdose were more likely to be diag- nificantly more cases receiving prescriptions for MED
nosed with other diseases and health conditions. The ≥50 mg per day and ≥100 mg per day. All selected
mean CCI score, which reflects general health status, was nonopioid drugs were also prescribed to cases signifi-
higher for cases than for controls (3.9 vs 1.7, P < 0.0001), cantly more often than to controls (Table 5).
indicating poorer overall health in the cases. As shown in
Table 4, cases reported particularly significantly higher fre- As shown in Table 6, cases had significantly greater health
quency during the 6-month baseline period of chronic care resource utilization than controls during the baseline
pulmonary disease (e.g., emphysema, chronic bronchitis, period, including outpatient office and ED visits, hospital-

Total paents, October 1, 2010 to September 30, 2012

(N = 10,131,467)

Paents with at least one opioid VHA Pharmacy claim

October 1, 2010 to September 30, 2012 (N = 1,877,841)

No Opioid-Related Serious Toxicity or Overdose (Controls) Opioid-Related Serious Toxicity or Overdose (Cases)

Paents not diagnosed with opioid-related serious Paents diagnosed with opioid-related serious
toxicity or overdose toxicity or overdose
October 1, 2010 to September 30, 2012 October 1, 2010 to September 30, 2012
(N = 1,876,765) (N = 1,076)

1) Paents with connuous medical and pharmacy Paents with connuous medical and pharmacy
benefits for at least 6 months before the index date benefits for at least 6 months before the index date
(N = 16,062) from whom 2) 10 were randomly (N = 817)
assigned to each case (N = 8170)

Figure 1 Sample selection flowchart.

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Table 3 Baseline demographic characteristics

Cases (N = 817) Controls (N = 8,170)

Characteristics N SD, % N SD, % P

Age (years), median (IQR) 62.0 10.0 62.0 16.0 <0.001

Age group (years)
18–34 27 3.3 565 6.9 <0.001
35–44 31 3.8 619 7.6 <0.001
45–54 115 14.1 1,240 15.2 0.402
55–64 377 46.1 2,672 32.7 <0.001
65+ 267 32.7 3,074 37.6 0.005
Male 753 92.2 7,528 92.1 0.980
Race/ethnicity
Non-Hispanic white 555 67.9 4,546 55.6 <0.001
Non-Hispanic black 83 10.2 1,300 15.9 <0.001
Hispanic 32 3.9 431 5.3 0.094
Other 147 18.0 1,893 23.2 0.001
Marital status
Never married 102 12.5 1,227 15.0 0.052
Married 351 43.0 4,246 52.0 <0.001
Separated 20 2.5 41 0.5 <0.001
Divorced 285 34.9 2,268 27.8 <0.001
Widowed 59 7.2 388 4.8 0.002
BMI (kg/m2)
Underweight (<18.5) 29 3.6 72.0 0.9 <0.001
Normal (18.5–24.9) 193 23.6 1,197 14.7 <0.001
Overweight (25.0–29.9) 224 27.4 2,070 25.3 0.193
Obese (≥30.0) 306 37.5 2,667 32.6 0.005
Missing 65 8.0 2,164 26.5 <0.001
US Census region
Northeast 75 9.2 824 10.1 0.411
North Central 190 23.3 1,745 21.4 0.208
South 270 33.1 3,258 39.9 <0.001
West 257 31.5 1,842 22.6 <0.001
Other 25 3.1 501 6.1 <0.001

BMI = body mass index; IQR = interquartile range; SD = standard deviation.

izations, and pharmacy visits. An ED visit occurred during were combined into one category. Endocarditis was not
the baseline period in 65% of cases compared with 21% included in the final logistic regression as it was reported in
of controls. Nearly half of the cases were hospitalized only one case patient. The final model yielded a c-statistic
during the baseline period at least once compared with of 0.89. As displayed in Figure 2, significant independent
9% of controls. demographic predictors of serious opioid toxicity included
ages 55–64 years and 65 and above, non-Hispanic white
During the 2-year study period, 159/817 case patients race, never married, widowed, and those receiving care in
died (19.5%) compared with 282/8,170 controls (3.5%). the western region of the United States.
Twenty of the deaths in the case patients occurred during
a VHA-treated episode of serious toxicity or overdose for Concomitant health conditions that were most strongly
an index event fatality rate of 2.4% (20/817). associated with the occurrence of serious opioid-related
toxicity or overdose were opioid dependence, moderate
Multivariable Analysis or severe liver disease, skin ulcers, metastatic solid tumor,
and pancreatitis. Other comorbidities significantly associ-
The logistic regression model for the dichotomous ated with the outcome included renal disease, bipolar
outcome of serious opioid-related respiratory/CNS disorder, traumatic injury chronic pulmonary disease, war-
depression or overdose resulted in multiple, independent, farin use, substance abuse, and sleep apnea (Figure 3).
statistically significant associations. To improve the esti-
mate stability, the marital status categories “separated” Prescription opioids containing hydromorphone or
(N = 20/817 cases) and “divorced” (N = 285/817 cases) oxycodone and those with ER/LA formulations were

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Table 4 Baseline clinical characteristics

Cases (N = 817) Controls (N = 8,170)

Comorbidities N SD, % N SD, % P

CCI score, mean (SD) 3.9 3.3 1.7 2.0 <0.001

Individual CCI comorbidities
Myocardial infarction 28 3.4 105 1.3 <0.001
Congestive heart failure 93 11.4 308 3.8 <0.001
Peripheral vascular disease 71 8.7 353 4.3 <0.001
Cerebrovascular disease 57 7.0 343 4.2 <0.001
Dementia 5 0.6 32 0.4 0.348
Chronic pulmonary disease 291 35.6 1,047 12.8 <0.001
Rheumatologic disease 6 0.7 96 1.2 0.257
Peptic ulcer disease 9 1.1 63 0.8 0.312
Mild liver disease 43 5.3 64 0.8 <0.001
Diabetes 263 32.2 1,850 22.6 <0.001
Hypertension 495 60.6 3,670 44.9 <0.001
Depression 357 43.7 1,562 19.1 <0.001
Use of warfarin 78 9.6 387 4.7 <0.001
Hemiplegia or paraplegia 13 1.6 34 0.4 <0.001
Renal disease 112 13.7 428 5.2 <0.001
Any malignancy, including leukemia and lymphoma 147 18.0 646 8.0 <0.001
Diabetes with chronic complications 92 11.3 432 5.3 <0.001
Skin ulcers 122 14.9 302 3.7 <0.001
Moderate or severe liver disease 28 3.4 19 0.2 <0.001
Metastatic solid tumor 46 5.6 59 0.7 <0.001
HIV/AIDS 11 1.4 42 0.5 0.003
Other selected comorbidities
Nonpain related
Substance abuse and nonopioid substance dependence 215 26.3 764 9.4 <0.001
Opioid dependence 105 12.9 97 1.2 <0.001
Endocarditis 1 0.1 9 0.1 0.920
Viral hepatitis 106 13.0 249 3.0 <0.001
Alcoholic hepatitis 3 0.4 5 0.1 0.005
Pancreatitis 24 2.9 49 0.6 <0.001
Sexually transmitted disease 12 1.5 69 0.8 0.072
Herpes simplex infection 7 0.9 45 0.6 0.272
Skin infections/abscesses 85 10.4 286 3.5 <0.001
Sleep apnea 147 18.0 652 8.0 <0.001
Tobacco use disorder 301 36.8 1,266 15.5 <0.001
PTSD 221 27.1 1,119 13.7 <0.001
Bipolar disorder 86 10.5 239 2.9 <0.001
ADHD 7 0.9 58 0.7 0.637
Schizophrenia 36 4.4 114 1.4 <0.001
Anxiety disorder 180 22.0 681 8.3 <0.001
OCD 5 0.6 19 0.2 0.045
Cardiovascular disease 172 21.1 764 9.4 <0.001
Obesity 150 18.4 1,072 13.1 <0.001
Pain related
Low back disorders 380 46.5 2,099 25.7 <0.001
Other back/neck disorders 214 26.2 1,048 12.8 <0.001
Neuropathic disorders 170 20.8 717 8.8 <0.001
Fibromyalgia 34 4.2 157 1.9 <0.001
Headache/migraine 88 10.8 427 5.2 <0.001
Burns 4 0.5 16 0.2 0.089
Traumatic injury 212 26.0 869 10.6 <0.001
Motor vehicle accidents 7 0.9 14 0.2 <0.001

ADHD = attention deficit hyperactivity disorder; AIDS = acquired immunodeficiency syndrome; CCI = Charlson Comorbidity Index, 2008
updated (score); OCD = obsessive–compulsive disorder; PTSD = post-traumatic stress disorder; SD = standard deviation.

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Table 5 Baseline prescription drugs dispensed by VHA

Cases (N = 817) Controls (N = 8,170)

Prescription Drug Use N SD, % N SD, % P

Opioid use 693 84.8 4,936 60.4 <0.001

By active ingredient
Hydrocodone 314 38.4 2,633 32.2 <0.001
Oxycodone 305 37.3 876 10.7 <0.001
Buprenorphine 0 0.0 2 0.0 0.655
Tramadol 114 14 1,428 17.5 0.011
Codeine 63 7.7 561 6.9 0.365
Fentanyl 49 6.0 44 0.5 <0.001
Morphine 251 30.7 334 4.1 <0.001
Hydromorphone 38 4.7 28 0.3 <0.001
Methadone 107 13.1 139 1.7 <0.001
Oxymorphone 1 0.1 1 0.0 0.044
Other* 2 0.2 4 0.1 0.039
By formulation
ER/LA‡ 369 45.2 499 6.1 <0.001
Short acting‡ 633 77.5 4,807 58.9 <0.001
Proportion of opioids = ER/LA† 0.25 0.3 <0.1 0.2 <0.001
By route
Oral 692 84.7 4,923 60.3 <0.001
Parenteral 6 0.7 6 0.1 <0.001
Transdermal 48 5.9 44 0.5 <0.001
Number of opioid prescriptions dispensed, mean (SD) 6.8 5.9 2.5 3.4 <0.001
Number of unique opioid NDCs, mean (SD) 2.4 1.9 0.9 1.1 <0.001
Maximum prescribed daily MED (mg), mean (SD) 98.7 122.1 24.2 48.4 <0.001
1–<20 35 4.3 1,331 16.3 <0.001
20–<50 227 27.8 2,614 32.0 0.014
50–<100 163 20.0 718 8.8 <0.001
≥100 268 32.8 273 3.3 <0.001
Selected nonopioid drugs 747 91.4 5,905 72.3 <0.001
Benzodiazepines 336 41.1 1,242 15.2 <0.001
Antidepressants 565 69.2 2,886 35.3 <0.001
Nonopioid analgesics 556 68.1 4,598 56.3 <0.001
Muscle relaxants 226 27.7 1,288 15.8 <0.001
Other sedatives 125 15.3 609 7.5 <0.001
Antipsychotics 239 29.3 772 9.5 <0.001
Stimulants 14 1.7 51 0.6 <0.001

* Other opioids include meperidine and pentazocine/naloxone.

†
Proportion of opioid prescriptions dispensed to a patient during baseline that contained an ER/LA formulation. Methadone is a
long-acting opioid.
‡
Percentages exceed 100% due to prescription of both ER/LA and short-acting formulations in some patients.
ER/LA = extended release/long acting; MED = morphine equivalent dose; NDC = National drug code; SD = standard deviation;
VHA = Veterans Health Administration.

significantly associated with increased risk of serious MED were 1.5 times as likely to experience life-threatening
opioid-related toxicity or overdose. The likelihood of expe- opioid-related respiratory/CNS depression or overdose
riencing the outcome was related monotonically to increas- (Figure 4). Coprescription of benzodiazepines, antidepres-
ing maximum prescribed daily MED of 20 mg or higher. sants, and antipsychotics in opioid users was significantly
Patients prescribed a maximum daily MED ≥100 mg during associated with experiencing serious toxicity or overdose.
the baseline period were more than four times as likely to
experience serious opioid-related toxicity or overdose Patients hospitalized for one or more days for any reason
compared with those prescribed MED of 1–<20 mg/day, during the baseline period were nearly three times as likely
whereas patients prescribed 50–<100 mg/day MED were to experience serious opioid-related toxicity compared
2.2 times as likely, and those prescribed 20–49 mg/day with those who were not hospitalized.

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Table 6 Baseline health care utilization

Cases (N = 817) Controls (N = 8,170)

All-Cause Health Care
Utilization N SD, % N SD, % P

Days of hospitalization, mean (SD) 9.6 22.9 1.1 8.0 <0.001

Patients with ≥1 outpatient ED visit 534 65.4 1,740 21.3 <0.001
Patients with ≥1 outpatient office visit 792 96.9 7,333 89.8 <0.001
Patients with ≥1 inpatient hospitalization 396 48.5 739 9.1 <0.001
Patients with ≥1 prescription fill 800 97.9 7,561 92.6 <0.001
Outpatient ED visits per patient, mean (SD) 2 2.6 0.4 1 <0.001
Outpatient office visits per patient, mean (SD) 23 18.6 9.8 11.3 <0.001
Inpatient hospitalizations per patient, mean (SD) 1 1.5 0.1 0.5 <0.001
Pharmacy visits per patient, mean (SD) 24.6 15.0 12.9 10.4 <0.001

ED = emergency department; SD = standard deviation.

Full regression results, including factors that were not dominantly US veterans. Consistent with published find-
statistically significantly related to the outcome in the logis- ings on prescription opioid overdose deaths, we found
tic model are provided in Appendix II. that certain demographic characteristics, comorbid con-
ditions, and medication-related factors were associated
Discussion with non-fatal prescription opioid-related serious toxicity
or overdose as well [16,21,45]. Demographic variables
Our study produced a robust multivariable model that previously identified as risk factors, and confirmed in the
characterized the risk of life-threatening opioid-related present study, included non-Hispanic white race, never
respiratory/CNS depression or overdose in medical users married and widowed marital status, and residence in the
of prescription opioids. Higher maximum prescribed daily Western United States [2,12,16,21,24,45,46]. These
MED, a history of opioid dependence, and hospitalization factors are likely to be proxies for underlying patient-
during the 6 months before the overdose or serious tox- related constructs, including genetic influences on drug
icity event were the factors most strongly associated with metabolism; the social environment, such as isolation; the
this outcome among an opioid-exposed cohort of pre- prescriber, including opioid-prescribing patterns; and the

Figure 2 Logistic regression results: significant demographic factors.

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Individual CCI Comorbidities

Chronic Pulmonary Disease***
Rheumatologic Disease*
Use of Warfarin*
Renal Disease***
Skin Ulcers***
Moderate or Severe Liver Disease*
Metastatic Solid Tumor**
Other Non-pain-related Comorbidities
Substance Abuse*
Opioid Dependence***
Pancreatitis*
Skin Infections/Abscesses*
Sleep Apnea*
Bipolar disorder**
ADHD*
Other Pain-related Comorbidities
Traumatic Injury***
Baseline All-cause Health Care Utilization
Hospitalizations ≥ 1 day***
* 0.01 ≤ p < 0.05
0 1 2 3 4 5 6
** 0.001 ≤ p < 0.01
Odds Ratio (95% Confidence Interval)
*** p < 0.001

Figure 3 Logistic regression results: significant comorbid conditions and health care utilization factors.

health care system, such as access to emergency care population or chronic pain patients not treated with
and other medical services [24,47–52]. opioids [11,33,56]. We observed that polypharmacy with
psychoactive drugs commonly prescribed for mental
Some of our findings differed from those of studies of fatal health disorders, such as benzodiazepines, antidepres-
opioid overdose. In contrast to the typical occurrence of sants, and antipsychotics, as well as mental illness itself,
opioid overdose death in middle age (peaking at 45–54 was involved in approximately one-half of overdose events
years), most case patients in our study were aged 55 [1,13,56,57]. The association between serious toxicity
years or older [8,12]. This discrepancy likely reflects the events among opioid users in this study and pharmaco-
older VHA population. The older age predominance also therapy for mental health disorders such as depression
affected the pattern of comorbidity in our study popula- and anxiety may be partially mediated by the substantially
tion, with chronic diseases and cancer being prevalent. higher prevalence of substance use disorders [56].
Physiologically older individuals have age-related impair-
ment in the hepatic and renal ability to metabolize and We found certain opioid characteristics to be highly asso-
excrete certain drugs and other substances and have a ciated with the likelihood of experiencing opioid-related
greater burden of disease and associated potentially inter- toxicity or overdose. Use of extended-release formulations
acting concomitant medications. Such individuals are bio- and long-acting opioids was strongly associated with an
logically vulnerable to opioid accumulation and to increased likelihood of overdose events, as reported pre-
experiencing toxicity even when using an opioid well within viously [27,30,58]. Methadone, a long-acting opioid, was
its recommended dosing range. The safe use of opioids also examined as an independent determinant due to its
long-term to manage chronic pain in elderly patients is long half-life, variable pharmacokinetics, and dispropor-
particularly challenging [39,53–55]. tionate involvement in 30–40% of all opioid-related deaths
despite accounting for only 5–19% of US opioids pre-
Another reported treatment challenge observed in our scribed [7,12,18,27,59]. In contrast to other studies
study population was the strong association of serious that focused exclusively on fatal overdose, methadone
respiratory/CNS depression or overdose with substance alone was not independently associated with serious
use disorders (dependence and abuse) and mental health respiratory/CNS depression or overdose events treated at
disorders (bipolar disorder). Abuse of alcohol, illicit VHA facilities, falling just short of the statistical significance
opioids, and other substances is more frequent among threshold (P = 0.08). It is unclear whether this difference is
medical users of prescription opioids than in the general due to the study sample’s relatively low prevalence of

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 Risk Factors Prescription Opioid Toxicity Overdose

Figure 4 Logistic regression results: significant prescription drug-related factors.

methadone dispensed and fatal outcomes or to organ impairment (liver, kidney, adrenal), potential interac-
other characteristic(s) of the study sample or model tions with concomitant nonopioid medications and sub-
specification. stances (e.g., benzodiazepines, alcohol), the direction of
the opioid switch, and incomplete cross tolerance
Our study confirmed the known dose-related toxicity of between opioids, as well as differences in the likelihood of
opioids. Importantly, maximum prescribed daily MED of as opioid-induced hyperalgesia and physical dependence.
little as 20 mg was associated with serious fatal and non- Some differences may be due to significant genetic vari-
fatal overdose and toxicity in opioid consumers overall. ants in opioid receptors, metabolism, and transport in the
Previous research identified a significant risk of overdose nervous system [65,66]. The current guidelines are based
death for daily MED of ≥20 or 50 mg in patients with on expert opinion and have not been validated for safety
chronic noncancer pain [21,25,60]. An increasing body of or efficacy [55,61,64,67].
scientific evidence suggests that prescriber overreliance
on, and inadequate proficiency using, opioid dose con- Of note, medical use of tramadol in our study appeared to
version factors or ratios in published equianalgesic dose be protective against serious opioid-related overdose (OR
tables to calculate MED is an important contributor in fatal 0.7, 95% CI, 0.5–1.0). Tramadol, a novel synthetic opioid
or near-fatal opioid-related CNS/respiratory depression analgesic with monamine reuptake inhibition contributing
[27,38,61–64]. The numerous published equianalgesic to its analgesic effect, has low mu opioid receptor binding
tables that are widely available contain inconsistent and affinity and is not currently regulated as a controlled sub-
variable conversion ratios. To reduce the risk of uninten- stance at the federal level in the United States [68–71].
tional serious toxicity when rotating or switching opioids, However, its US prescribing information contains warnings
updated guidelines for the safe use of equianalgesic dose similar to all prescription opioids regarding the risk of CNS
tables emphasize the need to consider the opioid conver- and respiratory depression, overdose, and death. This
sion ratio or calculated equianalgesic dose in morphine interesting study finding warrants further investigation.
equivalents as only an approximate starting point. The
calculated MED must then be adjusted for each individual Pain is a complex, multidimensional condition with a mul-
patient and clinical scenario by accounting for tiplicity of interacting and contributing influences [72].
interindividual sources of variation that can alter opioid Factors involved in the likelihood of serious opioid-related
potency. Such sources of individual variation include toxicity or overdose in individuals treated for painful con-
demographic differences (age, sex, race, ethnicity), major ditions relate to the patient and their social environment,

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 Zedler et al.

prescriber or other source of opioids, health care system, stances from unreported non-VHA sources, particularly in
and the specific opioid and other exposures. Although the case cohort which had a significantly higher preva-
pain is the most common reason a patient seeks medical lence of substance use disorders. In addition, the serious
care, current US data on the incidence, prevalence, and respiratory/CNS depression and overdose rate in this
treatment of pain are not complete or consistent, partly sample is likely an underestimate as we evaluated only
because it is considered a symptom. Recent evidence cases that fulfilled a stringent case definition and came to
indicates that approximately 80% of episodes of pain medical attention within VHA.
treated with opioids are short term [37]. However, an
estimated 100–116 million US adults suffer chronic pain Implications for Future Research
[53,72], and 3–4% of the adult population (9 million)
are prescribed opioids each year to manage chronic Future studies should assess the generalizability of these
noncancer pain [6–9,11]. Thus, the total population at risk findings to populations more representative of US medical
of life-threatening opioid-related respiratory/CNS depres- users of prescription opioids, including wider age ranges
sion or overdose is substantial. and more women. With a larger dataset, selected interac-
tions among risk factors should be evaluated, as well as
Our study confirms and extends findings from prior the predictive utility of behavioral and other factors not
research that focused on fatal overdoses but did not dif- routinely captured in administrative health care data (e.g.,
ferentiate between medical and nonmedical opioid users use of alcohol and other substances, other sources of
[13,16–18,21,60]. The relatively low frequency of fatal out- opioids, therapeutic indication, social conditions, setting
comes of serious opioid-related events in our VHA-treated of the overdose or serious toxicity event, family history).
cohort (2.4% over 2 years) suggests that the majority of Potential differences in risk factor profiles for overdose or
such events in medical users is not fatal. However, non- life-threatening respiratory/CNS depression among those
fatal events do place a substantial burden on the health treated with opioids for acute vs chronic conditions,
care system and patients [73,74]. chronic noncancer pain vs chronic cancer pain, and short
term vs long term should also be explored.
Strengths and Limitations
Conclusions
Major strengths of this study include the large, national
patient population as well as the rich detail of VHA admin- The risk of life-threatening toxicity, including overdose, in
istrative data. The robust statistical model included vari- medical users of prescription opioids is an alarming, esca-
ables that are readily available from medical and pharmacy lating public health problem. Substantial risk exists when
claims data. In contrast to most previous research, we even relatively low daily MED of opioids is used in patients
examined in a comprehensive and systematic fashion the who are vulnerable due to sociodemographic factors,
determinants associated with nonfatal as well as fatal concomitant medical and psychiatric conditions, and
serious toxicity and overdose related to the medical use of simultaneous use of other medications or substances.
prescription opioids. However, the study sample included Expert guidelines recommend screening all patients
all opioid-exposed patients and was stratified by neither before initiating opioids for pain management to identify
therapeutic indication or acuity (e.g., acute vs chronic pain those at elevated risk for serious adverse outcomes
conditions; chronic pain related to cancer vs noncancer) [26,55,75]. An extensive literature review revealed several
nor by the duration of opioid treatment (short term vs long available instruments to screen for aberrant drug-related
term), partly to avoid potential statistical challenges with behaviors (abuse, addiction, diversion) [55,76], but no
the limited number of cases available. Our study was instruments that provide useful, real-time, evidence-based
subject to many of the limitations commonly associated information to the prescriber regarding the risk of over-
with observational studies using administrative data dose or serious respiratory/CNS depression currently exist
(e.g., limited ability to infer causality and limited access to [55]. A public health imperative is the identification of
information regarding actual medication consumption/ medical users of prescription opioids who are at highest
adherence, other behavioral/social elements, and thera- risk of life-threatening toxicity for whom additional precau-
peutic indication, with the potential for residual tions should be considered. These precautions include
confounding). In addition, while VHA provides a large, education of the patient and caregivers, increased caution
national population from which to sample, generalizability in opioid selection and dose escalation, consultation with
is limited as the population comprises primarily older, pain management specialists, and close monitoring for the
white men who receive most of their health care within a emergence of opioid-related toxicity or known risk factors
single, closed system. for this outcome [28,55,75]. Additional measures to
reduce opioid-related morbidity and mortality may include
Limitations in accuracy and completeness are inherent in enhanced training and compliance of health care provid-
administrative data and include missing data, coding ers with evidence-based best practices for prescribing
errors, misclassification, and undiagnosed or undocu- opioids, such as considering coprescribing naloxone, par-
mented comorbidities such as substance use disorders. ticularly if delivery systems can be developed that are safe
While prescriptions dispensed within the VHA system are and more user friendly for nonmedical first responders
well documented, it is possible that patients in the study than the current syringe or nasal atomizer-based systems.
also consumed opioids and other medications or sub- Naloxone is a rescue medication with more than three

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 Risk Factors Prescription Opioid Toxicity Overdose

decades of proven effectiveness and safety in reversing 8 Manchikanti L, Fellows B, Ailinani H, Pampati V.
life-threatening opioid-related respiratory/CNS depression Therapeutic use, abuse, and nonmedical use of
or overdose [3,7,74,77–80]. opioids: A ten-year perspective. Pain Physician
2010;13(5):401–35.
The results of our study indicate that a statistically robust
model based on administrative medical, pharmacy, and 9 Parsells Kelly J, Cook SF, Kaufman DW, et al. Preva-
health care resource utilization data may help identify the lence and characteristics of opioid use in the US adult
demographic characteristics, comorbid conditions, con- population. Pain 2008;138(3):507–13.
comitant medications, and opioid-related factors associ-
ated with increased risk of life-threatening toxicity and 10 Sullivan MD, Edlund MJ, Fan MY, et al. Trends in use
overdose. These factors help to identify the individuals of opioids for non-cancer pain conditions 2000–2005
most likely to benefit from preventive interventions. The in commercial and Medicaid insurance plans: The
development and widespread use of a risk profiling TROUP study. Pain 2008;138(2):440–9.
questionnaire based on these factors to guide patient
treatment decisions would have the potential to signifi- 11 Sullivan MD, Edlund MJ, Steffick D, Unutzer J. Regular
cantly improve the balance between the analgesic use of prescribed opioids: Association with com-
benefit of opioid therapy and the risks of serious toxicity mon psychiatric disorders. Pain 2005;119(1–3):95–
or overdose and other adverse outcomes, including 103.
abuse, diversion for nonmedical use, and iatrogenic
addiction. 12 Warner M, Chen LH, Makuc DM, Anderson RN,
Minino AM. Drug poisoning deaths in the United
Acknowledgments States, 1980–2008. NCHS Data Brief 2011;(81):
1–8.
The authors of the study would like to acknowledge Juan
Du, MS, of STATinMED, Inc. for statistical programming 13 Paulozzi LJ, Kilbourne EM, Shah NG, et al. A history of
support and Elizabeth Moran of STATinMED, Inc. for being prescribed controlled substances and risk of
medical writing support on this project. drug overdose death. Pain Med 2012;13(1):87–95.

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Appendices

Appendix I

Prescription opioid drug products

Active Ingredient(s) by Generic Name

Alfentanil hydrochloride
Buprenorphine
Butorphanol tartrate
Codeine, acetaminophen
Codeine base
Codeine phosphate
Codeine phosphate, triprolidine, pseudoephedrine hydrochloride
Codeine phosphate, chlorpheniramine maleate
Codeine phosphate, guaifenesin, pseudophedrine
Codeine phosphate, pyrilamine maleate
Codeine phosphate, acetaminophen, gamma-aminobutyric acid
Codeine phosphate, brompheniramine maleate, pseudoephedrine hydrochloride
Codeine phosphate, brompheniramine maleate, phenylephrine hydrochloride
Codeine phosphate, butalbital, acetaminophen, caffeine
Codeine phosphate, butalbital, aspirin, caffeine
Codeine phosphate, carisoprodol, aspirin

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 Risk Factors Prescription Opioid Toxicity Overdose

Appendix I Continued

Active Ingredient(s) by Generic Name

Codeine phosphate, chlorcyclizine hydrochloride

Codeine phosphate, dexbrompheniramine maleate, pseudoephedrine hydrochloride
Codeine phosphate, guaifenesin, pseudoephedrine hydrochloride
Codeine phosphate, phenylephrine hydrochloride
Codeine phosphate, phenylephrine hydrochloride, diphenhydramine hydrochloride
Codeine phosphate, phenylephrine hydrochloride, chlorcyclizine hydrochloride
Codeine phosphate, phenylephrine hydrochloride, chlorpheniramine maleate
Codeine phosphate, phenylephrine hydrochloride, pyrilamine maleate
Codeine phosphate, promethazine hydrochloride
Codeine phosphate, promethazine hydrochloride, phenylephrine hydrochloride
Codeine phosphate, pseudoephedrine hydrochloride, chlorcyclizine HCl
Codeine phosphate, pseudoephedrine hydrochloride, chlorpheniramine maleate
Codeine phosphate, pseudoephedrine hydrochloride
Codeine phosphate, pseudoephedrine hydrochloride, pyrilamine maleate
Codeine sulfate
Dihydrocodeine bitartrate, acetaminophen, caffeine
Dihydrocodeine bitartrate, brompheniramine maleate, phenylephrine hydrochloride
Dihydrocodeine bitartrate, brompheniramine maleate, pseudoephedrine hydrochloride
Dihydrocodeine bitartrate, guaifenesin
Dihydrocodeine bitartrate, phenylephrine hydrochloride, guaifenesin
Dihydrocodeine bitartrate, phenylephrine hydrochloride, pyrilamine maleate
Fentanyl
Fentanyl citrate, bupivacaine HCl
Hydrocodone bitartrate, acetaminophen
Hydrocodone bitartrate, homatropine methylbromide
Hydrocodone bitartrate, ibuprofen
Hydrocodone bitartrate, chlorpheniramine maleate, pseudoephedrine hydrochloride
Hydrocodone bitartrate, pseudoephedrine hydrochloride
Hydrocodone polistirex, chlorpheniramine polistirex
Hydrocodone, acetaminophen, gamma-aminobutyric acid
Hydromorphone hydrochloride
Levorphanol tartrate
Meperidine hydrochloride
Methadone hydrochloride
Morphine
Nalbuphine hydrochloride
Naloxone, buprenorphine
Oxycodone, acetaminophen
Oxycodone, aspirin
Oxycodone hydrochloride
Oxycodone hydrochloride, ibuprofen
Oxymorphone hydrochloride
Pentazocine hydrochloride, acetaminophen
Pentazocine hydrochloride, naloxone hydrochloride
Pentazocine lactate
Propoxyphene hydrochloride
Propoxyphene hydrochloride, acetaminophen
Propoxyphene napsylate
Propoxyphene napsylate, acetaminophen
Sufentanil citrate
Tapentadol
Tramadol hydrochloride
Tramadol hydrochloride, acetaminophen
Tramadol hydrochloride, gamma-aminobutyric acid
Tramadol hydrochloride, acetaminophen

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 Zedler et al.

Appendix II

Logistic regression results: serious opioid-related toxicity or overdose

Covariate† Odds Ratio 95% CI P

Age group (years)

18–34 Reference
35–44 0.9 0.5 1.8 0.826
−45–54 1.4 0.8 2.4 0.224
55–64 1.9 1.1 3.3 0.014
65+ 1.8 1.1 3.2 0.028
Male 0.9 0.6 1.3 0.553
Race
Non-Hispanic black Reference
Non-Hispanic white 1.8 1.3 2.4 <0.001
Hispanic 1.4 0.8 2.4 0.248
Other 1.6 1.1 2.2 0.013
Marital status
Married (reference) Reference
Separated/divorced 1.1 0.9 1.4 0.404
Never married 1.4 1.0 1.8 0.044
Widowed 2.0 1.4 3.0 <0.001
Geographic region
Northeast (reference) Reference
North central 1.3 0.9 1.8 0.184
South 1.2 0.9 1.7 0.316
West 1.8 1.3 2.5 0.001
Other 0.7 0.4 1.2 0.154
Comorbidity
Individual CCI comorbidities
Myocardial infarction 0.8 0.4 1.4 0.345
Congestive heart failure 1.1 0.7 1.8 0.674
Peripheral vascular disease 1.1 0.8 1.7 0.502
Cerebrovascular disease 0.7 0.4 1.1 0.132
Dementia 1.0 0.3 3.1 0.977
Chronic pulmonary disease 1.5 1.2 1.9 <0.001
Rheumatologic disease 0.3 0.1 0.9 0.027
Peptic ulcer disease 0.5 0.2 1.2 0.123
Mild liver disease 1.6 0.9 3.2 0.137
Diabetes 1.1 0.9 1.4 0.418
Hypertension 1.0 0.8 1.3 0.791
Depression 1.2 1.0 1.5 0.105
Use of warfarin 1.4 1.0 2.0 0.040
Hemiplegia or paraplegia 0.9 0.4 2.3 0.867
Renal disease 1.7 1.3 2.4 0.001
Any malignancy, including leukemia and lymphoma 1.3 1.0 1.7 0.086
Diabetes with chronic complications 1.0 0.7 1.4 0.769
Skin ulcers 2.4 1.5 3.8 <0.001
Moderate or severe liver disease 2.7 1.1 6.7 0.036
Metastatic solid tumor 2.3 1.3 4.0 0.007
HIV/AIDS 2.0 0.8 4.8 0.120
Other Selected comorbidities
Nonpain related
Substance abuse and nonopioid substance dependence 1.4 1.0 1.8 0.031
Opioid dependence 3.9 2.6 5.8 <0.001
Viral hepatitis 1.4 0.9 2.0 0.098
Alcoholic hepatitis 0.7 0.1 10.9 0.823
Pancreatitis 2.2 1.1 4.5 0.032
Sexually transmitted disease 1.4 0.6 3.1 0.458
Herpes simplex infection 0.8 0.3 2.2 0.639
Skin infections/abscesses 0.5 0.3 0.9 0.010
Sleep apnea 1.3 1.0 1.8 0.040
Tobacco use disorder 1.2 1.0 1.5 0.066
PTSD 1.0 0.8 1.3 0.985
Bipolar disorder 1.7 1.2 2.4 0.005

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 Risk Factors Prescription Opioid Toxicity Overdose

Appendix II Continued
Covariate† Odds Ratio 95% CI P

ADHD 0.3 0.1 1.0 0.048

Schizophrenia 1.6 0.9 2.8 0.105
Anxiety disorder 1.1 0.9 1.5 0.384
OCD 0.6 0.1 2.8 0.552
Cardiovascular disease 1.3 0.8 2.0 0.243
Obesity 1.1 0.8 1.4 0.498
Pain related
Low back disorders 1.1 0.9 1.4 0.241
Other back/neck disorders 1.1 0.9 1.4 0.309
Neuropathic disorders 1.0 0.8 1.3 0.815
Fibromyalgia 1.2 0.7 2.0 0.574
Headache/migraine 1.2 0.8 1.7 0.322
Burns 0.8 0.2 3.8 0.758
Traumatic injury 1.6 1.3 2.0 <0.001
Motor vehicle accidents 2.4 0.7 7.6 0.145
Prescription drug use
Opioids
By active ingredient
Hydrocodone 1.0 0.8 1.4 0.779
Oxycodone 1.4 1.1 1.9 0.017
Tramadol 0.7 0.5 1.0 0.043
Codeine 1.3 0.9 1.9 0.146
Fentanyl 0.8 0.1 6.9 0.813
Morphine 1.6 1.0 2.5 0.079
Hydromorphone 2.4 1.2 4.7 0.012
Methadone 1.6 1.0 2.7 0.079
Oxymorphone 0.3 0.0 5.4 0.377
Other* 1.7 0.1 52.5 0.775
By formulation
Short acting Reference
ER/LA 1.9 1.1 3.2 0.018
By route
Oral Reference
Parenteral or transdermal 2.3 0.3 18.7 0.433
Number of opioid prescriptions dispensed, mean (SD) 1.0 1.0 1.0 0.852
Number of unique opioid NDCs, mean (SD) 1.0 0.9 1.1 0.488
Maximum prescribed daily morphine equivalent dose (MED, mg/day)
1–<20 (reference) Reference
20–<50 1.5 1.1 1.9 0.011
50–<100 2.2 1.5 3.2 <0.001
≥100 4.1 2.6 6.5 <0.001
Nonopioid drugs of interest
Benzodiazepines 1.4 1.1 1.7 0.004
Antidepressants 1.6 1.3 2.0 <0.001
Nonopioid analgesics 0.9 0.7 1.2 0.557
Muscle relaxants 1.1 0.9 1.4 0.293
Other sedatives 1.1 0.8 1.5 0.521
Antipsychotics 1.3 1.0 1.7 0.045
Stimulants 1.9 0.8 4.6 0.179
All-cause health care utilization during the preceding 6 months
Days of hospitalization
0 Reference
≥1 2.9 2.3 3.6 <0.001

* Other opioids included meperidine and pentazocine/naloxone. Methadone is a long-acting opioid.

ADHD = attention deficit hyperactivity disorder; CCI = Charlson Comorbidity Index; CI = confidence interval; ER/LA = extended
release or long acting; MED = morphine equivalent dose; NDC = National drug code; OCD = obsessive–compulsive disorder;
PTSD = post-traumatic stress disorder; SD = standard deviation.
†
Covariates with frequencies less than 10 or which prevented model convergence were not included in the full model.

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EXHIBIT G
EXHIBIT H