Opioid detoxification I Case series

Loperamide and P-glycoprotein

modulator in opioid detoxification
Mohamed Al Garhy MD, Sona Mohan MRCPsych, Aisha Al Dhufairi MRCPsych
Opioids contribute to 70% of Table 1. Patient diagnoses, COWS scores and additional treatment for withdrawal
the negative health impact
associated with drug use Patient Diagnoses according COWS score COWS score COWS Additional
disorders. A new opioid to DSM-5 on admission 2–3 days score on treatment besides
withdrawal protocol using before after starting discharge loperamide and
over-the-counter medications treatment treatment omeprazole

loperamide and P-glycoprotein 1 Opioids withdrawal 0 7 0 Quetiapine 50mg

inhibitor (omeprazole) was Cannabis use disorder Zopiclone 7.5mg
described by Dr Al Garhy
2 Opioids withdrawal 2 1 1 Quetiapine 200mg
previously. In this article the Stimulant use disorder
successful use of this protocol, Sedative use disorder
evidenced by the Clinical Opiate
3 Opioids withdrawal 1 12 1 Quetiapine 100mg
Withdrawal Scale, is discussed Lorazepam 1mg 3
in a case series. times daily

4 Opioids withdrawal 3 1 0 Quetiapine 200mg

In 2015, 29.5 million people Stimulant use disorder Escitalopram 30mg

around the world suffered from Sedatives use disorder
Cannabis use disorder
drug use disorders; opioids con-
tributed to 70% of the negative 5 Opioids withdrawal 6 5 0 Chlordiazepoxide
health impact associated with drug Stimulant use disorder 20mg 3 times daily
use disorders, and were considered Sedatives withdrawal
to be the most harmful substances Cannabis use disorder
of abuse. 1 According to DSM-5 Abbreviations: COWS: Clinical Opiate Withdrawal Scale
diagnostic criteria, opioid with-
drawal syndrome is defined as: alternatives (eg α2-adrenergic ago- medications loperamide and P-gly-
‘Three or more symptoms, devel- nists such as clonidine) or some- coprotein inhibitor (omeprazole)
oping within minutes to several times symptomatic medications (eg was suggested by the primary
days of ceasing or reducing opioid loperamide for diarrhoea).3,4 author in 2014, after proved effec-
use that has been heavy and pro- One of the most widely used tiveness in 44 patients undergoing
longed or administration of an scales to objectively measure the opioid withdrawal. 6 The study
antagonist after a period of opioid severity of opioid withdrawal symp- examined some of the safety and
use’. Withdrawal symptoms might toms and the response to with- effectiveness measures such as
include nausea, diarrhoea, fever, drawal treatment is the Clinical length of stay, side-effects and
muscle aches or insomnia.2 Opiate Withdrawal Scale (COWS). patients’ demands to increase
The focus for any opioid detox- It assesses both signs and symp- treatment dosage, but no scales
ification protocol is to complete toms of withdrawal. Items include were used to assess severity of
the process in a prudent, prag- anxiety or irritability, gastrointesti- withdrawal manifestations.
matic and productive manner. In nal upset, restlessness, bone or In this context we will present
health care settings, opioid detox- joint aches, sweating, rhinorrhoea, data from a series of five cases
ification classic approaches tremor, gooseflesh, yawning, pupil admitted for opioid withdrawal
include the use of opioid agonists size and pulse rate.5 management in the same unit (see
(eg methadone), partial agonists A new opioid withdrawal proto- Table 1). Loperamide and P-glyco-
(eg buprenorphine), non-opioid col using over-the-counter protein inhibitor (omeprazole)

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Case series I Opioid detoxification

were used for opioid withdrawal with no increase in the doses of which were all revealed to be
management and COWS was used the previously added medications. unremarkable. The initial treat-
to assess withdrawal symptoms Withdrawal symptoms were ment regimen comprised of quet-
severity on a daily basis, during improving gradually. Eight days iapine 200mg, omeprazole 20mg
the course of admission. after admission, COWS total score twice daily, and loperamide 2mg
was 0 (no withdrawal). He was dis- three times daily. On day 3 of his
Case 1 charged home after completion of inpatient stay, the COWS total
This case refers to a 35-year-old detoxification with a plan to eval- score was 1 (no withdrawal). On
married man, of Arab ethnicity, uate him every week in the outpa- day 5, the COWS total score was 1
working in a regular office job, tient department. He was seen (no withdrawal). The patient did
who was admitted to the substance twice after discharge and reported not have any complaints nor any
misuse inpatient unit through the to be still abstinent. signs of withdrawal throughout
outpatient clinic within the same his hospital stay. He was dis-
facility. The patient initially had Case 2 charged home after completing
no complaints; he was keen to be A married, unemployed, 27-year- the detoxification course, on que-
admitted to the inpatient detoxifi- old man, was admitted to the sub- tiapine 200mg with a plan to visit
cation service. He had a history of stance misuse inpatient unit the outpatient department weekly,
increasing use of cannabis and through the outpatient clinic but he did not show up.
opioids – mainly morphine intra- within the same facility for a short-
venously, up to 5mg daily – contin- term detoxification program. The Case 3
uously for the past three months. patient, who was self-referred, This case refers to a 35-year-old
There was no significant history of reported a three year history of single man, who had admitted
other mental health disorders or polysubstance misuse. He was himself voluntarily to the sub-
alcohol misuse. He was prescribed administering heroin intrave- stance misuse inpatient unit
quetiapine 50mg at bedtime for nously, up to 1g daily, along with through the outpatient clinic
insomnia in another psychiatric methamphetamine intravenously. within the same facility. He had a
facility before admission to man- In addition to that, he was abusing two-year history of increasing use
age his sleep problems. Mental benzodiazepines (mainly alpra- of opioids. He was using mor-
state examination and neurologi- zolam, clonazepam and diaze- phine intravenously, up to 1.5mg
cal examination, on admission, pam), orally, continuously for the daily for the past two years. At the
were unremarkable. Blood work same time period. He used to time of evaluation he was com-
up results and electrocardiogram smoke two joints of cannabis daily plaining of interrupted sleep and
were insignificant. for three years as well. His last mild anxiety. His last dose of mor-
On the day of admission, dose of all mentioned substances phine was on the same morning of
COWS total score was 0 (no with- was three days prior to admission. admission. He did not have signif-
drawal), as he had had the last The patient reported using quet- icant history of medical or other
dose of morphine the same morn- iapine 200mg for his sleep distur- psychiatric disorders. Mental state
ing. The initial treatment regimen bances, which was prescribed to examination and neurological
administered included omepra- him from a another clinic. There examination were unremarkable.
zole 20mg twice daily, loperamide is no significant history of medical On the day of admission,
2mg three times daily, and his or other psychiatric disorders. He COWS total score was 1 (no with-
50mg quetiapine at bedtime, as was admitted for rehabilitation in drawal). The initial treatment reg-
prophylactic treatment for antici- three different facilities, one of imen included quetiapine 100mg
pated withdrawal symptoms. them being mandated by a court at bedtime, lorazepam 1mg three
Two days after admission, the order aimed at compulsory reha- times daily, omeprazole 20mg
patient reported having general- bilitation for a period of four twice daily, and loperamide 2mg
ised body aches, chills and sweat- months. Mental state examination three times daily. On day 2 COWS
ing, diarrhoea and difficulty on admission was unremarkable. total score was 12 (mild with-
sleeping. COWS total score was 7 On the day of admission, COWS drawal). He was complaining of
(mild withdrawal). Zopiclone total score was 2 (no withdrawal). generalised body ache, vomiting
7.5mg as needed was added to Routine blood workup was ordered and diarrhoea. Medications were
help with the occasional insomnia along with electrocardiogram, continued at the same doses and

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Opioid detoxification I Case series

the patient was examined fre- COWS total score was still 1 (no did not show for his clinic
quently. On day 7 COWS total withdrawal). The discharge plan appointments.
score was 1 (no withdrawal) and was to visit the outpatient clinic
he was discharged home on quet- weekly. He never showed up for Discussion
iapine 100mg at bedtime. The his appointments. This case series is to further high-
discharge plan was to assess him light the effectiveness of opioid
every week in the clinic. He was Case 5 detoxification using loperamide
seen three times after discharge A single 24-year-old unemployed and P-glycoprotein modulator.
and reported to be still abstinent. man, who was transferred to sub- Whereas the withdrawal process
stance misuse unit from acute for opioids is seldom life threat-
Case 4 internal medicine unit after ening in comparison with that for
This case refers to a 29-year-old being admitted for opioid and alcohol owing to the likelihood
married man who had lost his job benzodiazepines intoxication. He for seizures and delirium, the
in the police due to his substance used morphine intravenously, up to physical uneasiness renders it dif-
misuse problem. The patient pre- 0.5mg daily, for the previous four ficult to tolerate.7
sented to outpatient clinic volun- years, along with amphetamine Loperamide is a P-glycopro-
tarily asking for admission to the injections, cannabis, benzodiaze- tein substrate, which is a cheap,
substance misuse unit for sub- pines and pregabalin in high doses widely available, over-the-counter
stance detoxification. He had a for almost the same duration. drug that acts primarily in the
history of polysubstance misuse. On admission he complained gastrointestinal tissues to treat
He was injecting heroin, intrave- of interrupted sleep, anxiety, low diarrhoea. It was reported that if
nously, up to 1g daily for the past mood and fatigue, but had stable used in larger than recom-
three years, along with abusing vital signs. He did not have any mended doses it can penetrate
methamphetamine, cannabis and significant history of medical or the blood brain barrier and have
benzodiazepines for the same other psychiatric disorders. methadone-like effect. Further-
period. At the time of evaluation, Forensic history was significant more, it has been reported that
he did not have any complaints of with two periods of imprisonment loperamide has been used among
withdrawal-like symptoms or for illegal use of substances. Men- users of opioids to manage opi-
intoxication. His last doses of all tal state examination and neuro- oids discontinuation symptoms. 8
mentioned drugs were three days logical examination were Loperamide is a phenylpiperi-
before admission. He did not unremarkable. dine derivative and µ-opioid
have a significant history of med- On the day of admission receptor agonist, does not readily
ical or other psychiatric disor- COWS total score was 6 (mild cross the blood-brain barrier and
ders. Mental state examination withdrawal – he had insomnia thus has minimal impact on the
and neurological examination and anxiety). The initial treat- central nervous system. As it is a
were unremarkable. ment regimen included omepra- P-glycoprotein substrate, co-ad-
On the day of admission, zole 20mg twice daily, loperamide ministering it with a P-glycopro-
COWS total score was 3 (no with- 2mg three times daily and chlor- tein inhibitor such as omeprazole
drawal). The initial treatment reg- diazepoxide 20mg three times (a proton pump inhibitor) would
imen included quetiapine 200mg daily. On day 3 COWS total score support breaching this barrier,
at bedtime, escitalopram 30mg was 5 (mild withdrawal). The converting it from a peripheral-
once daily (his regular treatments patient did not report worsening ly-acting µ-opioid receptor ago-
before admission), omeprazole of withdrawal symptoms. On day n i s t t o t r e a t d i a r rh o e a t o a
20mg twice daily, and loperamide 5 omeprazole and loperamide central-acting opioid agonist that
2mg three times daily. On day 2 were discontinued as the patient reduces the full spectrum of opi-
COWS total score was 1 (mild reported no withdrawal symp- oid withdrawal manifestations. 9
withdrawal). The patient did not toms. Chlordiazepoxide was The effectiveness of loperamide
develop any withdrawal symptoms reduced gradually to 10mg twice and omeprazole as part of an opi-
during admission, but he did not daily. On day 7 COWS total score oid detoxification protocol was
seem to be motivated to continue was 1 (no withdrawal) and he was examined in a retrospective
the detoxification program. He discharged with a plan to follow study, published in 2014, by the
was discharged on day 3 when his up weekly in the clinic. He primary author. 6 The study had

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Case series I Opioid detoxification

examined patients’ characteris- 7, respectively). On the other Declaration of interests:

tics and treatment outcomes of hand, patient number two had No conflicts of interest were
44 patients admitted for opioid not complained of any withdrawal declared.
detoxification in a substance mis- symptoms (COWS score of 1 on
use inpatient unit in a tertiary day 1 and day 5 – discharge day). Dr Al Garhy, Dr Mohan and Dr Al
hospital, in Abu Dhabi, UAE, over Although patient number four Dhufairi are psychiatrists at Sheikh
a two year period. Length of stay, had also not exhibited any with- Khalifa Medical City, Abu Dhabi,
serious adverse events, side-ef- drawal symptoms (COWS score of United Arab Emirates.
fects and ‘requested increased 3 and 1 on day 1 and day 2 respec-
doses of protocol medication’ tively), they did not complete the References
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28 I Progress in Neurology and Psychiatry I Vol. 25 Iss. 3 2021 wchh.onlinelibrary.wiley.com