104 年台灣成癮學會 北區持續教育(一)

日 期：104 年 5 月 23 日 (星期六) PM 14:00~18:30

地 點：莉蓮會館 (台北市內湖區堤頂大道一段 327 號)
主 辦 單 位：台灣成癮科學學會

Time Topic Speaker Moderator

13:30-14:00 Registration 報到

14:00-14:10 Opening 黃三原 理事長

Methamphetamine and Ketamine 陳志根 主任 李新民 院長

14:10-15:00
related disorder 基隆長庚醫院 部立桃園療養院

Neurobiology of opioid and its 黃三原 理事長

antagonist 台灣成癮科學學會
周孫元 主任
15:00-15:50 Clinical experience of Methadone 武維馨 主任 部立桃園療養院
and Buprenorphine in patient with
部立基隆醫院
heroin addiction.
15:50-16:10 Breaking

How to monitor of drug abuse in 蔡維禎 主任 諶立中 副局長

16:10-1700
Taiwan 台北榮總 毒物科 新北市衛生局

How to treatment in Ketamine 蒙 恩 主任 萬芳榮 教授

17:00-17:50
Cystitis: surgical approach 三軍總醫院 泌尿科 國防部軍醫局
蔡維禎 主任 諶立中 副局長
蒙 恩 主任 萬芳榮 教 授
18:00-18:20 Discussion
武維馨 主任 李新民 院 長
黃三原 理事長 周孫元 主任
＊台灣成癮科學學會 4 學分、精神醫學會繼續教育 3 學分及衛福部藥癮治療繼續教育時數 3 小時。
＊上課資料以 Textbook of substance abuse treatment, AJP 2014 年出版為主; 臨床及研究經驗當
輔助教材。此次上課內容為成癮次專科醫師考題內容
1
Chih-Ken Chen, M..D. Ph.D.

Dr. Chen is a professor of psychiatry at the Chang Gung University School of Medicine. He received
an M.D degree at Yang Ming University in 1991, and received his doctorate in psychiatry from
King’s College, University of London in 2001. His main research interests are within the theme
of etiology of mental disorders. Long-term use of methamphetamine can result in physical
and mental complications including methamphetamine psychosis. He has studied
various predisposing factors to methamphetamine-induced psychosis. He is also interested
in molecular genetic studies in psychotic disorders, substance abuse and attention deficit hyperactivity
disorder. He found that the domamine transporter gene is associated with attention deficit hyperactivity
disorder in a Taiwanese sample. He also conducted association studies on methamphetamine
abuse or methamphetamine psychosis with some candidate genes. His study suggests
that a continuum of vulnerability to psychosis accounts in part for individual differences
in liability to methamphetamine psychosis, and provides preliminary evidence that
COMT play certain roles in the abuse of methamphetamine. He reported recently that
persistence of psychotic symptoms as an indicator of cognitive impairment in
methamphetamine users. Dr. Chen is currently leading a project of translational studies
of ketamine related disorders.

Related publications
1. Chen CK, Lin SK, Chen YC, Huang MC, Chen TT, Ree SC, Wang LJ. Persistence of psychotic
symptoms as an indicator of cognitive impairment in methamphetamine users. Drug Alcohol
Depend. 2015 Mar 1;148:158-64.
2. Chen CK, Lin SK, Chiang SC, Su LW, Wang LJ. Polymorphisms of COMT Val158Met and
DAT1 3'-UTR VNTR in Illicit Drug Use and Drug-Related Psychiatric Disorders. Subst Use
Misuse. 2014 Sep;49(11):1385-91.
3. Wang LJ, Chiang SC, Su LW, Lin SK, Chen CK*. Factors Associated with Drug-related
Psychiatric Disorders and Suicide Attempts among Illicit Drug Users in Taiwan. Substance Use
& Misuse. 2012 Aug;47(10):1185-8.
4. Jugurnauth SK, Chen CK ( Joint first author), Barnes MR, Li T, Lin SK, Liu HC, Collier DA,
Breen G. A COMT gene haplotype associated with methamphetamine abuse. Pharmacogenet
Genomics. 2011 Nov;21(11):731-40.
1
Methamphetamine and Ketamine
Related Disorders

安非他命與愷他命相關疾患

陳志根
Chih-Ken Chen MD PhD
Chung Gung University School of Medicine
Chang Gung Memorial Hospital

Seizures of amphetamine-type
stimulants

Global (in tons)

South-East Asia (in kg)

World Drug Report 2014 by United Nations Office on Drugs and Crime

1
 Physical consequences of MA use
• Cardiovascular: cardiomyopathy, myocarditis,
hypertension, arrhythmia, myocardial infarction, rapid
heart beat.
• Pulmonary: pulmonary edema, dyspnea, bronchitis,
pulmonary hypertension, hemoptysis, chest pain, asthma
exacerbation, pulmonary granuloma.
• Neurological: strokes, seizure, chronic headache,
cerebral swelling and hemorrhage, involuntary
movement and tics.
• Hepatic: liver disease in 40% of MA users
• Others: dental problems, skin lesions,….
• Obstetric complications: low birth weight
-- Rawson, Ling & Mooney 2015. Clinical Management: Methamphetamine. In:
Textbook of Substance Abuse Treatment 5th ed.

METH Mouth

-- Chiang et al. Taiwan J Psychiatry (2013)

2
 Psychiatric consequences of MA use

• Psychosis
• Depression
• Anxiety
• Suicidality
• Aggression and violence

-- Rawson, Ling & Mooney 2015. Clinical Management: Methamphetamine. In:

Textbook of Substance Abuse Treatment 5th ed.

Prevalence of psychosis among

regular MA users
• 13 % psychosis
• 23% clinically significant suspiciousness,
unusual thought content or hallucinations
• 11 times higher than general population
• Dependent: non-dependent = 3:1

Mcketin et al 2006 Addiction

3
 Symptoms of MA-induced psychosis

• Persecutory delusions
• Ideas of reference
• Hallucinations (visual, auditory, olfactory, tactile)
• Stereotypic and compulsive acts
• Blunt affect, poverty of speech
• Prone to excited delirium and violence

-- Rawson, Ling & Mooney 2015. Clinical Management: Methamphetamine. In:

Textbook of Substance Abuse Treatment 5th ed.

Symptoms of MA psychosis

90.0% 84.5%
80.0% 71.7%
70.0% 62.8%
60.0% N = 174
46.5%
50.0% 40.5%
40.0% 28.1% 27.3%
30.0%
20.0%
10.0%
0.0%
ns

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us

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-- Chen CK et al. Psychol Med (2003)

4
 Premorbid schizoid & schizotypal traits

8
PSST

• MNP-R: regular MA users

7 N = 204
with no MA psychosis
6 5.6 • MNP-O: occasional MA
5 4.7 users with no MA psychosis
4.3
3.8 • MIP-B: MA users with brief
4 MA psychosis
3 • MIP-P: MA users with
prolonged MA psychosis
2
1
0
MNP-R MNP-O MIP-B MIP-P
-- Chen CK et al. Psychol Med (2003)

Morbid risk for schizophrenia

among relatives of MA users
7.0% 6.5%
Morbid risk

• MNP-R: regular MA users

6.0%
N = 445 with no MA psychosis
5.0% • MNP-O: occasional MA
users with no MA psychosis
4.0%
• MIP-B: MA users with brief
3.0% 2.4%
MA psychosis
• MIP-P: MA users with
2.0% prolonged MA psychosis
0.9%
1.0% 0.5%

0.0%
MNP-R MNP-O MIP-B MIP-P

--Chen CK et al. (2005) Am J Med Genet

5
Neurotransmitter imaging on MA psychosis

• Striatal DAT binding was decreased in MA abusers. After two-week abstinence, the DAT binding
was partially recovered (Chou et al 2007)
• A substantial increase in DAT after a longer abstinence (Volkow et al 2001)

Neurocognition in MA psychosis
and schizophrenia

--Jacob et al 2008 Cogn Behav Neurol

6
 Cognition in MA abuse/psychosis

--Chen et al Drug and Alcohol Dependence (In Press)

General course of MA psychosis

other substances
repeated use re-administration of abuse liability
fatigue, insomnia,
psychological stressor
onset of psychotic relapse relapse spontaneous relapse
episode

susceptibility
to persistent
psychotic state psychosis

treatment
clinical course
-- Courtesy of Kazufumi Akiyama

7
 Managing MA intoxication with
agitation
• Talking down
• Haloperidol 5 mg oral or IM + lorazepam 1-2 mg
• Atypical antipsychotic oral or IM + lorazepam 1-2 mg

-- Rawson, Ling & Mooney 2015. Clinical Management: Methamphetamine. In:

Textbook of Substance Abuse Treatment 5th ed.

Managing MA withdrawal

• Rest, exercise and a healthy diet

• Short-acting BZD for agitation and sleep disturbance
• Withdrawal-associated depression and cognitive
deficits generally resolve without intervention
• Drug craving managed through behavioral treatment,
no specific medications proven effective.

-- Rawson, Ling & Mooney 2015. Clinical Management: Methamphetamine. In:

Textbook of Substance Abuse Treatment 5th ed.

8
 Treatment guidelines for
acute MA psychosis
• For treatment of patients in emergency setting
• Aims: safe containment and management of
disturbed individual and to restore sleep
Oral BZD

fail

I.M. BZD
fail

Sedative antipsychotic
Success fail

Review use of antipsychotic

within 3 days

-- McIver et al 2006

Treatment for MA psychosis

• Lack of evidence based guidelines
• Mainly drawn from the literature addressing
schizophrenia
• If antipsychotics are indicated, atypical
antipsychotics are preferred.
• Case studies* show good response to
quetiapine, risperidone and olanzapine.
• Olanzapine is identified as suitable for patient in
emergency setting because of availability of oral
an I.M preparation. (McIver et al 2006)

* Misra & Kofoed 1997; Misra et al 2000; Dore & Sweeting 2006

9
 Pharmacotherapy for MA use
disorders (clinical trials)
• Bupropion:
– Effective for increasing the number of weeks of abstinence in
low-to-moderate MA dependence (Elkashef et al, 2008)
– No significant treatment effects on stimulant-use outcomes
(Winhusen et al, 2014)
• Naltrexone reduces craving level and amphetamine use (Jayaram-
Lindstrom et al, 2008)
• Mirtazapine decreased MA use and sexual risk in men who have
sex with men (Colfax et al, 2011)
• Topiramate does not promote abstinence in MA users but can
reduce the amount taken and reduce relapse rates in those who are
already abstinent. (Elkashef et al, 2012)
• Aripiprazole not effective (Coffin et al, 2013)
• Modafinil not effective (Anderson et al, 2012)

Behavioral treatments for MA

use disorders
• CBT
• Contingency management
• Matrix Model (Rawson et al. 2004):
– CBT
– Family education
– Motivation interviewing
– 12-step program

10
 Drugs seized in Taiwan
kg

-- Adapted from Ministry of Justice, Taiwan

Ketamine
• First introduced as an anesthetic in 1964
• Antagonist at one of the three glutamate
receptors: NMDA receptor
• Minor effects:
– Activation of dopamine release
– Weak agonist at mu opioid receptors
– Blocks muscarinic acetylcholine receptors

--Morgan & Curran 2011 Addiction

11
 --Nutt et al 2007 Lancet

Ketamine bladder
• Ketamine-induced ulcerative cystitis
• Frequency and urgency of urination, dysuria, urge incontinence,
occasionally painful hematuria
• Cystoscopy findings similar to chronic interstitial cystitis
• Etiology unclear

--Chu et al 2007 Lancet

12
 Ketamine for treatment-resistant depression
• 0.5 mg/kg infusion over 40 mins

-- Zarate et al 2006 Arch Gen Psychiatry

Repeated-dose ketamine for

treatment-resistant depression
• 0.5 mg/kg infusion over 40 mins (days1, 3, 5, 8, 10, and 12)
• 8 of 9 relapse after repeated dose ketamine infusion (mean 19 days
after 6th infusion)

-- ann het Rot et al 2010 Biological Psychiatry

13
 Depression
• Depression increased in daily users and ex-ketamine users

-- Morgan et al 2010 Addiction

Psychosis
• One dose of ketamine induces transient positive and
negative symptoms of schizophrenia in healthy
volunteers
• Ketamine causes resurgence of psychosis in stable
schizophrenics
• Daily ketamine users shows symptoms of schizophrenia
prodrome

--John Krystal et al 1994 Arch Gen Psychiatry

--Lahti et al 1995 Neuropsychopharmacology
--Malhotra et al 1997 Neuropsychopharmacology
-- Morgan et al 2009 Addiction

14
 Subanesthetic effects of ketamine
• Similar to the positive and negative symptoms of schizophrenia
• Alterations in perception
• Symptoms similar to dissociative states
• Impaired neurocognitive performance

--John Krystal et al 1994 Arch Gen Psychiatry

Dependence and withdrawal

• Majority of frequent users report using ketamine without

stopping until supplies run out
• Compulsive patterns of behavior
• Key problem: craving
• Withdrawal: craving, anxiety, shaking, sweating...

-- Morgan et al 2008 Psychol Med

15
Neurocognition in ketamine-induced
thought disorder and schizophrenia

--Adler et al 1999 Am J Psychiatry

Translational studies on
ketamine-related disorders
計 畫 項 目主 持 人服 務 單 位 系 所職 稱計 畫 名 稱

總計畫 愷他命相關疾患之轉譯研究
陳志根 長庚大學醫學系 教授

子計畫一
王亮人 高雄長庚醫院兒童心智科 主治醫師 建立中文版藥物及酒精依賴半結構式評估工具

子計畫二
愷他命使用疾患神經調節物質與細胞激素在戒
陳志根 長庚大學醫學系 教授 斷後的變化

子計畫三
利用動物成癮模式探討愷他命依賴性型成的分
陳景宗 長庚大學生物醫學研究所 教授 子機制

子計畫四
嘌呤受體與蕈毒鹼受體在愷他命膀胱炎病患組
吳俊德 基隆長庚醫院泌尿科 主治醫師 織中之表現

子計畫五
余兆松 長庚大學分子生物學科 教授 愷他命膀胱炎之細胞機轉及新潁尿液生物標誌

32

16
 Psychological Craving in Ketamine
Abusers

Effects of ketamine or MA abuse/psychosis

on cognition

Verbal Working Motor Verbal Attention and Executive Composite

memory memory speed fluency processing function score
speed
P-value P-value P-value P-value P-value P-value P-value
Age N.S. N.S. N.S. N.S. N.S. N.S. N.S.
Sex (male vs. female) N.S. N.S. N.S. N.S. N.S. N.S. N.S.
Length of education N.S. 0.006 N.S. N.S. N.S. N.S. 0.025
Drug abuse
Ketamine <0.001 N.S. N.S. 0.038 <0.001 N.S. 0.001
MA 0.005 N.S. N.S. 0.004 0.001 N.S. 0.030
Healthy control Ref Ref Ref Ref Ref Ref Ref
Drug psychosis
K-P N.S. N.S. N.S. 0.031 N.S. N.S. N.S.
K+BP 0.002 N.S. N.S. N.S <0.001 N.S. 0.002
K+PP 0.001 N.S. N.S. 0.034 <0.001 N.S. 0.001
MA-P N.S. N.S. N.S. N.S N.S. N.S. N.S.
MA+BP N.S. N.S. N.S. 0.012 0.012 N.S. N.S.
MA+PP <0.001 0.026 0.002 <0.001 <0.001 0.001 <0.001
Healthy control Ref Ref Ref Ref Ref Ref Ref

N=156 (Ketamine: 51, MA: 50, Control: 55)

BACS: Brief Assessment of Cognition in Schizophrenia; N.S. non-significant

17
 BACS among subgroups of ketamine
users and MA users

K–P: ketamine users without psychotic experience, K+BP: ketamine users with brief psychosis, K+PP: ketamine
users with prolonged psychosis, MA–P: MA users without psychotic experience, MA+BP: MA users with brief
psychosis, MA+PP: MA users with prolonged psychosis

Ketamine Addiction: animal model
• Ketamine addiction model:
1) Conditioned Place Preference (CPP): drug rewarding
2) Behavioral Sensitization: simulate drug relapse

• Neural substrates underlying ketamine addiction:

1) D1 pathway: AC/PKA/pDARPP‐32/pCdk5/pCREB/ΔFosB
2) D2 pathway: pAkt/pGSK3/β‐catenin/mTOR/Ser2448
3) DA signal:  pTH/Ser40
4) Glu signals: NMDAR, AMPAR subunits, pERK1/2
→ Crosstalk between DA and Glu pathways

18
 2014-10-14 BUC-005-1 (40X)

Day 6 (2014/10/20) Day 9 (2014/10/23) Day 16 (2014/10/30)

2014-10-14 BUC-005-2 (40X)

Day 6 (2014/10/20) Day 9 (2014/10/23) Day 16 (2014/10/30)

Purinergic receptors and muscarinic receptors in ketamine cystitis

Morphological changes after Ketamine treatment

NB‐Apex :              Control K 0 mM                                                    Test   K 
4mM

NB‐ NB‐ BC‐5637 BC‐

Test ( K  Apex Dome  T24
4mM;24H)
(phase;5x10)

3
8

19
Lamotrigine reduces ketamine experiences

• Ketamine induces secondary increases in

glutamate release
• Lamotrigine: glutamate release inhibitor

--Deakin et al 2008 Arch Gen Psychiatry

20
 Collaborators: MA
Japan
Taiwan
Kazuhiko Nakamura
Chih-Ken Chen
Hiroshi Ujike
Liang-Jen Wang
& The Japanese Genetics
Ming-Chyi Huang
Initiative for Drug Abuse
Shih-Ku Lin
Hsing-Cheng Liu
El-Wui Loh

USA UK
George Uhl Gerome Breen
Tao Li
David Collier

41

Collaborators: Ketamine
USA
Taiwan
John Krystal
Chih-Ken Chen
Joel Gelernter
Liang-Jen Wang
Ke Xu
Jin-Chung Chen
Bao-Zhu Yang
Chun-Te Wu
Jau-Song Yu
Yi-Ting Chen
Hsu-Yu-Chao
Ming-Chyi Huang
Shih-Ku Lin

42

21
1
 Prof. San-Yuan Huang

Prof. San-Yuan Huang graduated in medicine at the National Defense Medical Center,
Taipei, Taiwan, ROC. He completed his psychiatry residency at Tri-Service General
Hospital, Taipei, Taiwan. After psychiatry resident training, Dr. Huang received his Ph.D.
degree also from the National Defense Medical Center. His academic research focuses on
gene-gene, and gene-behavior-environment interaction in substance use disorders such as
alcohol dependence, depressive alcoholism and other illegal drug abuse. After Ph.D.
degree, he main academic interests/ research are in gene, brain image with SPECT and
PET, psycho-immunology in addiction and mental related disorder.

Currently Dr. Huang is the president of Taiwanese society of addiction science (TSAS).
He is also a professor in Psychiatry at National Defense Medical Center, and the Director
of the Department of Psychiatry at the Tri-Service General Hospital. He is active in
addiction services, particularly in the rehabilitation of addictive patients and promotion of
mental health in the addiction.

Prof. Huang has published more than one hundred and ten original paper, and he serves
on various journal/ and grant review committees including NSC/ MOD, NHRI and
NRPB….. research study sections.

黃三原 近三年著作目錄(2015-5-20 更新)

SCI (Original article, only corresponding author)
2015
1. Yeh YW, Ho PS, Chen CY,…..Lu RB, *Huang SY (correspondence) Suicidal ideation
modulates the reduction in serotonin transporter availability in male military
conscripts with major depression: a 4-[18F]-ADAM PET study. World J Biol
 Psychiatry. Accepted on 7 May 2015. (2013 Impact factor: 4.225; 26/134 on
psychiatry)
2. Yeh YW, Kuo SC, Chen CY,…..Lu RB, *Huang SY (correspondence) Harm
avoidance involved in mediating the association between nerve growth factor
(NGF) gene polymorphisms and antidepressant efficacy in patients with major
depressive disorder J Affect Disord. Accepted on 1 May. 2015
3. Chang HA, Chang CC, Kuo TB, *Huang SY (correspondence) Distinguishing
bipolar II depression from unipolar major depressive disorder: Differences in
heart rate variability. World J Biol Psychiatry. 2015 Mar 24:1-10. (2013
Impact factor: 4.225; 26/134 on psychiatry)
4. Tzeng NS, Lu RB, Yeh HW, Yeh YW, Huang CC, Yen CH, Kuo SC, Chen CY,, , Chang
HA, Ho PS, Cheng S, Shih MC, *Huang SY (correspondence) The dopamine
transporter gene may not contribute to susceptibility and the specific personality
traits of amphetamine dependence. Drug and Alcohol Dependence 2015 Apr
1;149:100-7. (2013 Impact factor: 3.23; 4/18 on substance abuse)
5. Yeh YW, Ho PS, Kuo SC, Chen CY, Liang CS, Yen CH, Huang CC, Ma KH, Shiue CY,
Huang WS, Shyu JF, Wan FJ, Lu RB, *Huang SY (correspondence) Disproportional
reduction of serotonin transporter may predict the response and adherence to
antidepressants in patients with major depressive disorder: a positron emission
tomography study with 4-[18F]-ADAM. Int J Neuropsychopharmacol. 2015 Jan 18
(7) 1-12 (2014-12 accepted) (2013 Impact factor: 5.264; 18/134 on Psychiatry)
6. Huang CC, Lu RB, Yen CH, Yeh YW , Chou HW, Kuo SC, Chen CY, Chang CC, Chang
HA, Ho PS, Liang CS, Cheng S, Shih MC, *Huang SY (correspondence) Dopamine
transporter gene may be associated with bipolar disorder and its personality
traits. EUR ARCH PSY CLIN N (2014-12 accepted) (2013 Impact factor: 3.355;
39/134 on Psychiatry)
7. Yeh YW, Chen CJ, Jang FL, Kuo SC, Chen CY, Liang CS, Ho PS, Yen CH, Shyu JF,
Wan FJ, Lu RB, *Huang SY (correspondence) SLC6A2 variants may predict
remission from major depression after venlafaxine treatment in Han Chinese
population. J Psychiatr Res. 2015 Feb;61:33-9. (2013 Impact factor: 4.092;
27/134 on Psychiatry)
8. Liang CS, Ho PS, Yen CH, Yeh YW, Kuo SC, Hung CC, Chen CY, Shih MC, Ma KH Lu
RB, *Huang SY (correspondence) Reduced striatal dopamine transporter density
associated with working memory deficits in opioid-dependent male subjects: a
SPECT study, Addict Biol (2014-11 PDF Proof) (2013 Impact factor: 5.929; 1/18
on substance abuse)
9. Yeh YW, Ho PS, Chen CY, Kuo SC, Liang CS, Ma KH, Shiue CY, Huang WS, Cheng CY,
Wang TY, Lu RB, *Huang SY (correspondence) Incongruent reduction of
serotonin transporter associated with suicide attempts in patients with major
depressive disorder: a positron emission tomography study with 4-[18F]-ADAM.
Int J Neuropsychopharmacol. 2014 Oct 31;18(3)1-9. (2012 Impact factor: 5.641;
13/135 on Psychiatry)
2014

10. Chang CC, Chang HA, Chen TY, Fang WH, *Huang SY (correspondence) Sex-
Specific Association Between Nerve Growth Factor Polymorphism and Cardiac
Vagal Modulation. Psychosomatic Medicine, 2014 Oct;76(8):638-43. (2013
Impact factor: 4.085; 28/134 on Psychiatry; 11 of 126 in Psychology )
11. Chang CC, Chang HA, Chen TY, Fang WH, *Huang SY (correspondence) Brain-
derived neurotrophic factor (BDNF) Val66Met polymorphism affects sympathetic
tone in a gender-specific way. Psychoneuroendocrinology 2014 Sep;47:17-25.
(2013 Impact factor: 5.591; 13/134 on Psychiatry)
12. Chang HA, Chang CC, Tzeng NS, Kuo TB, Lu RB, *Huang SY
(correspondence) Heart rate variability in unmedicated patients with bipolar
disorder in the manic phase. Psychiatry Clin Neurosci. 2014 Sep;68(9):674-82.
13. Kuo SC, Yeh YW, Chen CY, Huang CC, Chang HA, Yen CH, Ho PS, Liang CS, Chou
HW, Lu RB, *Huang SY (correspondence). DRD3 variation associates with early-
onset heroin dependence, but not specific personality traits. Prog
Neuropsychopharmacol Biol Psychiatry. 2014 Jun 3;51:1-8. (2013 Impact factor:
4.025; 33/194 on clinical neurology; 29/135 on Psychiatry)
2013

14. Chang HA, Chang CC, Tzeng NS, Terry Kuo BJ, Lu RB, *Huang SY
(correspondence). Generalized anxiety disorder, comorbid major depression and
heart rate variability: a case-control study in Taiwan. Psychiatry Investig. 2013
Dec;10(4):326-35
15. Huang CC, Lu RB, Shih MC, Yen CH, *Huang SY(correspondence) Dopamine
transporter gene possibly affects personality traits in patients with early-onset
major depressive disorder. Acta Neuropsychiatrica, 2013; 25: 227-234
16. Ho PS, Ho KJ, Huang WS, Yen CH, Shih MC, Shen LH, Ma KH, *Huang SY
(correspondence) Association study of serotonin transporter availability and
SLC6A4 gene polymorphisms inpatients with major depression. Psychiatry
Research: Neuroimaging. Psychiatry Res. 2013 Jun 30;212(3):216-22. (original
article, 3/14 on Neuroimage)
17. Chang HA, Chang CC, Tzeng NS, Terry Kuo BJ, Lu RB, *Huang SY(correspondence).
Cardiac autonomic dysregulation in acute schizophrenia. Acta Neuropsychiatrica,
2013; 25: 155-164.
18. Chang HA, Chang CC, Chen CL, Terry Kuo BJ, Lu RB, *Huang SY(correspondence).
Heart rate variability in patients with fully remitted major depressive disorder.
Acta Neuropsychiatrica, 2013: 25: 33-42.
19. Chang HA, Chang CC, Tzeng NS, Terry Kuo BJ, Lu RB, *Huang SY(correspondence).
 Decreased cardiac vagal control in drug naive patients with panic disorder: a case
control study in Taiwan. Asia-pacific psychiatry. 2013 Jun;5(2):80-9.
20. Chang HA, Chang CC, Tzeng NS, Terry Kuo BJ, Lu RB, *Huang SY(correspondence).
Decreased cardiac vagal control in drug-naive patients with posttraumatic stress
disorder. Psychiatry Investig. 2013 Jun;10(2):121-30.
21. Chen TY, Chen CY, Yen CH, Kuo SH, Yeh YW, Chang S, *Huang SY
(correspondence). Acute parietal lobe infarction presentingas Gerstmann’s
syndrome and cognitivedecline mimicking senile dementia . Neuropsychiatric
Disease and Treatment 2013:9 937–940
2012

22. Chen, CY; Lu RB; Yeh, YW; Shih MC; Huang SY* (correspondence) Association
study of catechol-O-methyltransferase gene polymorphisms with schizophrenia
and psychopathological symptoms in Han Chinese. Genes Brain Behav. 2011
Apr;10(3):316-24 (original article, 2010 Impact factor: 4.061; 6/48)
23. Huang CC, Lu RB, Shih MC, Yen CH, Huang SY* (correspondence) Association
Study of the Dopamine Transporter Gene (DAT1) with Personality Traits and
Major Depressive Disorder in the Han Chinese Population. Pharmacogenet
Genomics. 2011 Feb; 21(2):94-7. (original article, 2009 Impact factor: 3.991;
38/236 on Pharmacology & Phamacy, NSC99-2314-B-019 MY3)
24. Yeh YW, Lu RB, Tao PL, Shih MC, Huang SY*. (correspondence) A possible
association of the norepinephrine transporter gene polymorphism in the
development of heroin dependence in Han Chinese. Pharmacogenet Genomics.
2011 21(4):197-205. (original article, 2009 Impact factor: 3.991; 38/236 on
Pharmacology & Pharmacy)
25. Ho PS, Shih MC, Ma KH, Huang WS, Ho KJ, ,Yen CH, Lu RB, San-Yuan
Huang* (correspondence) Availability of the serotonin transporter in patients
with alcohol dependence. World J Biol Psychiatry. 2011 Mar;12(2):134-42.
(original article, 2009 Impact factor: 5.564; 08/117 on Psychiatry) (NSC95-
2314-B-016 -019 –MY2; NSC97-2314-B-016-001-MY2)
26. Huang SY*, Chen HK, Ma KH, Shy MJ, Chen JH, Lin WC, Lu RB (First and
correspondence) (2011), Association of promoter variants of human dopamine
transporter gene with schizophrenia in Han Chinese. Schizophrenia Research 116
(1) 68-74 (original article, 2009 Impact factor: 4.458; 18/117 on Psychiatry)
 104年台灣成癮科學學會 北區 持續教育

Neurobiology of opioid and

it antagonists
三軍總醫院 精神醫學部
國防醫學院 醫 學 系
黃三原 教 授
Prof. San-Yuan Huang

Outline for This Talk

I. Endogenous Opioid system

II. Neurobiology of tolerance, Dependence, and Addiction

III. Endogenous and Exogenous Opioid Role in Stress

responsibility

IV. Opioid detoxification

V. Opioid antagonists

Page 1
Endogenous Opioid neuropeptide and their Receptors
Opioid peptide Classes Opioid Receptor Types
ß-Endorphins (POMC) Mu (): MOPRa (from OPRM1 gene)
Enkephalins (PENK) Delta():DOPRa/MOPR (from OPRD1 gene)
Dynorphins (PDNY) Kappa(): KOPRa (from OPRK1 gene)
Nociceptin/orphanin (opioid-like) NOPR b
  
H2
N

Extracellular S
fluid
AA identical in 3

S receptors

AA identical in
2 receptors

AA different in
3 receptors
cell membrane

cell interior
HOOC

LaForge, Yuferov and Kreek, 2000

Opioid Receptors

 自然合成 : Heroin , codeine, hydromorphine
 人工合成 : Methadone, Buprenorphine, morphine
demerol, pentazocine, propoxyphene
 Opiate receptor : 
 : analgesia, euphoria, respiratory depression,       
constipation, dependence.
 : analgesia, diuresis, sedation
 : possibly with analgesia

Page 2
 Endogenous opioid peptide:
1.Endorphine (α, β, γ enkephalin)
2. dynorphin

Internationalization, receptor cycling, desensitization

Page 3
 Signal Transduction Mechanism
Internationalization, receptor cycling, desensitization
clathrin coated pit

Signal Transduction Mechanism

Page 4
 Signal Transduction Mechanism

Role of Mu Opioid Receptor and Related Endorphin

Systems in Normal Physiological Functions*
1. Endogenous Response to Pain

2. Neuroendocrine Functions
- Stress responsive systems including
hypothalamic-pituitary-adrenal axis

- Reproductive function including

hypothalamic-pituitary-gonadal axis

3. Immunological Function
4. Gastrointestinal Function
5. Cardiovascular/ Pulmonary Function
6. (？) Mood, Affect; Cognition, Memory, reward.

* All disrupted by chronic abuse of the short acting opiate, heroin

Page 5
Page 6
Opioid effect in endocrine function ?

Page 7
Outline for This Talk

I. Endogenous Opioid system

II. Neurobiology of tolerance, Dependence, and Addiction

III. Endogenous and Exogenous Opioid Role in Stress

responsibility

IV. Opioid detoxification

V. Opioid antagonists

Page 8
 Tolerance  dependence  addiction

• Dependence and tolerance are not

synonymous

• Addiction and dependence are often

inappropriately used
interchangeably, but they represent
two related but distinct and
dissociable phenomena

• Opioid receptor internalization,

recycling, and desensitization plays a
roles in the development of tolerance.

Pharmacotherapeutic agents for heroin addiction :

neurobiological profiles

• L-methadone : high efficacy agonist at MOPR; and a weak

NMDA receptor antagonist (this may be relevant to the
decreased tendency for methadone tolerance in maintenance
patients).

• Buprenorphine-naloxone combination formulation:

Buprenorphine is a slowly dissociating partial agonist at
MOPR, and it also exhibits low efficacy actions at KOPR.

• Depot formulation of the antagonist naltrexone:

approved in USA. Depot naltrexone provides an
approximately month-long blocked of MOPR

Page 9
 Mary Jeanne KreekJ Clin Invest. 2012;122(10):3387-3393

Mechanism of action

Buprenophine has quite a long effect, 48 hours, due to its slow

dissociation from the opioid receptors.

Page 10
Product Information of Buprenorphine

Suboxone film strip Desud Plus Suboxone

Outline for This Talk

I. Endogenous Opioid system

II. Neurobiology of tolerance, Dependence, and Addiction

III. Endogenous and Exogenous Opioid Role in Stress

responsibility

IV. Opioid detoxification

V. Opioid antagonists

Page 11
Figure 19-1, Stress responsive HPA axis in heroin addiction

POMC (Pro-opiomelanocortin ):
1. ,, Melanocyte
stimulating hormone
2. ACTH
(andrenocorticotropic hormone)
3. -lipoprotein
4. -endorphine

• profound disruption of the Stress

responsive HPA axis in occurs during
cycles of heroin addiction
• Normalization occurs during
methadone maintenance treatment

Mary Jeanne Kreek, Nature Neuroscience 8, 1450 - 1457 (2005)

Page 12
Genetic and epigenetic effects on MOPR function
• The A118G SNP : 10-25 % (Caucasian descent); 40-50 (Asia
descent), 0-2% (Africa descent); this SNP was functionally
different from the prototype receptor.

• The -endorphine bound with threefold greater affinity to

MOPR expressing this A118G SNP than to the prototype
receptor.

• Different binding affinity; G-protein coupled inwardly

rectifying potassium channels; different MOPR on cell
surface and OPRM1 RNA expression

• Pharmacogenetic study : SNP influence the Tx outcome of

naltrexone in alcoholism

Human Mu Opioid Receptor:

Location of Coding Region SNPs
(SNPs Resulting in Amino Acids Changes
or Synonymous Mutation)

Kreek, LaForge, Yuferov, 2005

Page 13
Outline for This Talk

I. Endogenous Opioid system

II. Neurobiology of tolerance, Dependence, and Addiction

III. Endogenous and Exogenous Opioid Role in Stress

responsibility

IV. Opioid detoxification

V. Opioid antagonists

Treating Opioid Addiction: Steps

 Getting off opioids: detoxification
– Agonist opioid based detoxification
– Non‐opioid based detoxification
– Antagonist based detoxification
 Staying of opioids: relapse prevention
– Agonist maintenance: methadone/others
– Antagonist maintenance: naltrexone
– Partial agonist maintenance: buprenorphine
 Changing life style

Page 14
 Detoxification

Purp0se: Methods and Medications:   
1. Relieve Symptoms of   Methadone and buprenorphine
withdrawal – Opioids agonist and partial agonist
2. Reverse neuro‐adaptation  – Short and long term  
from chronic heroin use  Clonidine and Lofexidine
3. Reduce degree of physical  – Non‐opioids; 
dependence α2 adrenergic receptor agonists
4. Promote long term treatment   Antagonists assisted
leading to life style changes – Naloxine / Naltrexone
5. Transitional treatment  – Rapid and ultra‐rapid
strategy detoxifications

Phases of Opioid Withdrawal

1. Anticipatory withdrawal (3‐4 hrs) 3. Fully Developed Withdrawal 
Fear of withdrawal (1‐3 days)
Anxiety  Severe anxiety     Tremor
Drug seeking Restlessness       Piloerection
2. Early withdrawal (8‐10hrs) Muscle spasm Vomiting
Anxiety                        Dilated pupils Elevated BP         Diarrhea
Restlessness              Lacrimaiton Fever/Chills          Tachycardia
Hypertension           Rhinorrhea Drug seeking
Tachycardia Nasal stuffiness   4. Protracted Abstinence
Sweating                   Yawning (up to 6 mos.)
Abdominal cramps    Nausea  Hypotension Loss of appetite
Drug seeking Bradycardia Loss of energy
Insomnia Cue induces craving

Page 15
 The concept
of substitute treatment

• Use long acting opioid medication to replace “short 
acting opioid (heroin) use behavior”
• Harm reduction approach
• Addicted relapsing rate usually high – treatment 
period takes months to years 

Opioid Substitution or 
Maintenance Therapy
 Reduce symptoms & signs of  Maintenance Medication:
withdrawal  Methadone maintenance 
 Reduce or eliminate craving (agonist)
 Blocks effects of illicit opioids  Naltrexone (antagonist)
 Restored normal physiology  Buprenorphine (partial agonist)
 Promote psychosocial  – Buprenorphine (Subutex)
rehabilitation and non‐drug life  – Buprenorphine‐naloxone (Desud; 
style Suboxone)

Page 16
 Outline for This Talk

I. Endogenous Opioid system

II. Neurobiology of tolerance, Dependence, and Addiction

III. Endogenous and Exogenous Opioid Role in Stress

responsibility

IV. Opioid detoxification

V. Opioid antagonists

Opioid antagonists
Three main indication for treating opioid use disorders:
1. To treating opioid overdose.

2. To shorten the duration of opioid detoxification.

3. To prevent relapse and foster long-term recovery (with long acting

opioid antagonist; e.g. depot naltrexone).

During maintenance treatment : its block or attenuate the

reinforcing effect or over-dose risk if a patient resumes opioid use.

 It may also reduce relapse and attenuate stress, cue, or priming induced
craving across a broad spectrum of addictive disorder

Page 17
Page 18
Evolution of pharmacologic treatments
Disulfiram -- 1950s
Methadone -- 1960s
Naltrexone (opioids) -- 1984
Nicotine -- gum ‘84; patch ‘92; nasal spray ‘96; inhaler ‘97
LAAM -- 1993
Naltrexone (alcohol) -- 1995
Buprenorphine -- France 1996; U.S. 2002
Bupropion -- 1997
Acamprosate -- Europe 1989; U.S. 2004
Naltrexone (extended release, alcohol) -- 2006
Varenicline -- 2006

Evolution of pharmacologic treatments: Naltrexone

Naltrexone developed in late 1970s/early 1980s
(approved for use in U.S. 1984)
A “behavioral pharmacotherapy” -- idea of extinction
central to its use; patients would no longer respond
to cues once reinforcing effects of opioids not
experienced
Poor compliance by patients
 IM depot formulation (Vivitrol) : FDA approval for alcohol
dependence (2006); for opioid dependence (2010)

Page 19
 Special considerations in Opioid antagonist

• Severe opioid withdrawal：if physically dependent on opioids.

• Common AE: nausea/ vomiting, headache, dizziness, fatigue/ or

sleepiness, insomnia, anxiety, decrease appetite

• Increase HPA and HPG activity: via inhibitory effects of –

endorphin on the hypothalamus.

• Poor medication adherence

• High attrition from treatment

• High rates of relapse to illicit opioid use

• High risk of overdose following treatment dropout raise

Page 20
 武維馨主任簡歷
學歷：
國立台北大學犯罪學研究所碩士

高雄醫學院醫學系

經歷：

台北市立療養院 (現台北市立聯合醫院松德院區) 住院醫師

振興復健醫學中心精神科總醫師

衛生福利部基隆醫院精神科主治醫師兼主任

內政部警政署基隆港務警察局心理諮商顧問

經國管理學院及崇右技術學院學輔中心顧問
1
 替代治療大事記（一）
 95年2月：替代療法試辦計畫（28人）
Clinical experience of Methadone and
 95年10月：擴大替代療法計畫（574人）
Buprenorphine in patient with heroin addiction
 96年1月：可近性替代療法補助計畫
（1551人）
衛生福利部基隆醫院精神科  97年1月：愛滋防治計畫補助初診費
武維馨 4600元（11526人）
97年8月：初診費補助終止（13295人）

替代治療大事記（二）
 98年7月：醫事處補助初診費2600元及
給藥費20元/日（11386人）
 99年9月：啟動監獄美沙冬維持治療試辦計畫 基隆監獄美沙冬治療試辦計畫簡報
 100年6月：醫事處部分補助丁基原啡因藥品費
99年9月～101年12月
24元/日（11906人）
 101年8月：依留置率調整丁基原啡因補助為
24元/日～100元/日（11736人）
 102年1月：因應監獄美沙冬試辦計畫終止，開
始在監提供suboxone治療

1
內容大綱
一. 建置過程與治療模式
二. 服務成果統計
三. 執行現況初報及分析
四. 成本會計效益分析
五. 討論與建議 建置過程與治療模式

硬體建置 硬體建置

醫療專用診間及電腦連線設備 美沙冬給藥室及儲藥保險櫃 醫療專用診間及電腦連線設備 醫院藥劑師入監稽核

2
治療模式 每週二診，每日美沙冬給藥
 新入監：戒癮門診評估、戒斷解毒及
美沙冬維持治療
 在監中：團體心理治療
 出監前：藥癮衛教宣導、再施用風險評估及美沙冬
新收初診作業

醫師看診情形 護理師給藥

每週一次團體心理治療 出監前三個月：再犯評估

出監前置團體衛教 出監前置評估

3
 門診診次及就診人次統計

診次 人次

服務成果統計 藥癮門診 224 1581

一般精神科門診 112 1662

合計 336 3243

資料自99年9月開辦，目前累計至101年12月底

新入監毒品犯治療狀況 在監中毒品犯團體心理治療狀況
 新入監受刑人評估後建議治療比例42.9%  99年11月開始服務，共8梯次團體心理治療，團體帶
領106次，服務1061人次。
 經評估建議治療後願意參加美沙冬替代治療比例為38%
70
 累計收案56人，服藥5537人次 團體次數 團體人次
60 60
60 56
入監評估 建議治療 入監初診 服藥 53
48 48 48
人數 人數 收案數 人次 50 46 47
44 44
46 47 46 47

340 146 56 5537 40 36

39
34
36 36
32
30 30
30
 備註:「建議治療」定義:戒斷量表(COWS)>8分 24 24

 資料自99年12月開辦，目前累計至101年12月底 20

10
5 4 4 4 4 4 5 4 4 4 5 5 4 5 4 4
3 3 3 3 3 3 3 3 2
0
99年11月

99年12月

100年1月

100年2月

100年3月

100年4月

100年5月

100年6月

100年7月

100年8月

100年9月

100年10月

100年11月

100年12月

101年1月

101年2月

101年3月

101年4月

101年5月

101年6月

101年7月

101年8月

101年9月

101年10月

101年11月

4
 出監前衛教宣導及再犯評估狀況 出監前再犯評估及美沙冬初診開案狀況
 99年10月開始辦理至12月底總計辦理26場替代療 • 出監衛教評估總計評估217人次，建議治療人數215人，建
法衛教，服務225人次。 議治療比例99.0%
• 實際接受美沙冬治療者6人，願意於出監前治療者所佔比
14 衛教人數
例為2.7%
12
12 12
• 在監曾接受替代治療且已刑滿出獄者共計6人，其中1人僅
治療5天即於出監前退案，4人係經由出監前評估接受治療
11 11 11
10 10 10 10 10 10
10
9 9 9 9 9 後出獄，1人係於新入監時即持續治療至出獄。目前5人均
8
8 8
在個管追蹤中，追蹤率100%
6 6 • 刑滿出獄者在監未接受替代治療，出監後自行報名來院報
名美沙冬有22人
6
5
4
4
3

2 出監前評估 建議治療 出監前新收 出監後追蹤 出監後自行

人數 人數 案人數 人數 報名人數
217 215 6 5 22
0
99年10月

99年11月

99年12月

100年1月

100年2月

100年3月

100年4月

100年5月

100年6月

100年7月

100年8月

100年9月

100年10月

100年11月

100年12月

101年2月

101年3月

101年4月

101年5月

101年6月

101年7月

101年8月

101年9月

資料自99年9月開辦，累計至101年12月底

新入監一級毒品犯之生理戒斷程度
新入監
人數 比例
全部戒斷程度

0-4分：輕度 178人 52%

執行現況初報及分析
5-12分：中度 88人 26%

13-24：中重度 65人 19%

25-36分：重度 9人 3%

備註：最低0分，最高30分，平均分
數6.3分，為中度戒斷

5
 新入監接受美沙冬治者之戒斷程度 退出原因統計
退出美沙冬治療原
新入監美沙冬治 人數 比例
人數 比例 因
療者之戒斷程度
個案自行要求退出 23 43%
0-4分：輕度 15人 27％

醫師建議終止治療 20 38%
5-12分：中度 18人 32％

家人不支持 3 6%
13-24：中重度 18人 32％

刑滿出獄 3 6%
25-36分：重度 5人 9％
非自願因素
4 7%
（移監，犯規等）

出監前再犯評估及美沙冬初診開案情形
 出監衛教評估總計評估217人
 建議治療人數215人，比例99%
 實際接受美沙冬治療者6人，比例為2.7%
 出監衛教評估後刑滿出獄158位
 22位已開始在醫院接受治療(5位監獄轉介，17位 成本會計效益分析
自行來院報名)

6
後

二年期計畫案成本效益分析
治療模式 人力 成本費用 申報收入 損益 醫院自辦矯正機關美沙冬治療成本概算
專任美沙冬 2400元 ×365天 1,752,000 執行人力 人力單價 業務執行頻率 人力成本（年） 備註
美沙冬 個案管理師 ×2年 元 282,840 負2,544,360
戒癮門診 精神藥癮 1,075,200 元 元
4800元 × 224診 精神科 4800元/診 每週2診 499,200 比照補助案診
專科醫師 元
專科醫師 看診時數半日 次費用計算
團體
心理治療 心理師 2400元× 106次 254,400元 美沙冬 2000元/天 365天 365,000 以月薪45000
專任個管師 給藥工時半日 元/22天計算
替代療法 2400元× 2人 藥師 2500元/天 每週1次 65,000 以月薪55000
宣導衛教 護理師 × 26次 124,800元 盤點工時半日 元/22天計算
保全 1000元/天 每週1次 26,000 以月薪22000
戒護工時半日 元/22天計算
申請衛生署建置之「醫療機構替代治療作業管理系統」需符合中央衛生主管機關指
定為替代療法執行機構： 司機 1000元/天 365天 182,500 以月薪22000
• 應有醫師、藥師及護理人員至少各一名。每年應接受8小時藥癮繼續教育講習。 接送工時半日 元/22天計算
• 醫師應具有管制藥品使用執照。
• 不能提供心理、職能治療或社會工作等相關服務者，應與中央衛生主管機關指定 計畫案補助收入(年） 醫院自辦成本（年） 醫院自辦收入（年）
藥癮戒治醫院訂定合作契約。
1,413,600 (-1,272,180) 1,137,700 (-996,280) 141,420
• 計畫書、管制藥品登記證 等中央衛生主管機關指定之文件。

由醫療角度檢視試辦效果
 試辦期間新入監初診共評估340名毒品收容人
 有一半的收容人有戒斷症狀
 有三成的收容人有中重度以上的戒斷症狀
 直接入監的241名毒品犯中(扣除自看守所移入99名個案)，
討論與建議 有六成以上的個案達中重度（COWS>12）的戒斷症狀

從WHO受刑人最低處遇標準及臨床醫療觀點，
持續提供監獄內毒品收容人生理解毒及戒斷治
療，確實有其必要

7
 由醫療角度檢視試辦效果 由犯罪預防檢視試辦效果
 看守所內之毒品收容人推估應普遍亦有嚴重戒斷症狀
 將近2成的個案，雖然不願意在監獄即開始治療，
 精神科專科醫師人力有限，恐難長期支援高診次之專 但於出監復發後，可自行前往醫院求助
業醫師人力 建立良好醫病關係與正確的治療認知，以利個案
於復發後主動迅速求治，或許比強求個案於出監
建議法務部可就監所特色及收容人類別重 前接受治療，更符合病患需求與醫療倫理。
新規劃，設立毒品犯收容專監
 高達6成以上的新入監收容人曾接受過美沙冬治療，
而同意在監接受治療者，全數均曾有美沙冬治療
之正向經驗
建議司法處遇前端即盡量增加社區處遇之比例或
將社區美沙冬治療納入假釋條件或刑後強制治療
之保安處分

由成本效益檢視試辦效果： 由受刑人觀點檢視試辦效果
 新入監個案較有接受美沙冬治療的需求，然而此治療仍以  新入監之毒品犯年齡以31～50歲居多，佔80.9％，且55％
解除戒斷症狀為階段性目標，而非維持治療。而出監前個 入監前是有穩定工作的狀態
案普遍無接受美沙冬治療之意願，利用率不到3％
 毒品犯之婚姻狀態係以單身無伴侶者為大宗，佔79％，社
 專任個管師人事成本(約52萬)+戒護人力、藥品管理、行
政業務及網路設備等間接成本 會支持系統不佳將導致其更不易重回正常家庭系統
 丁基原啡因治療1～2週，每日藥費約65～260元，則一年
累計之藥費約2～16萬元，遠低於美沙冬之人事成本 擴大緩起訴、緩刑等司法轉向處遇比例，令其
 102年1～5月基隆監獄一級毒品入監人數84人，自費使用
丁基原啡因治療人數23人，利用率27.4％，自費購藥費用 以附命條件強制接受社區美沙冬治療，將可減
共計31200元 少毒品犯因入監服刑而切斷社會依附，並符合
修復式正義之精神。
丁基原啡因無成癮性、效果好而副作用低，用
藥之安全性及社會接受度遠高於在監獄提供美
沙冬

8
 由受刑人觀點檢視試辦效果
 毒品施用者學歷絕大多數以國中高中學歷為主，佔
84.8％
團體心理治療以及出監前之衛教宣導，課
程設計應符合中等學歷知能
103年度基隆監獄一級毒品犯
 毒品施用者若無法真正正視戒毒的困難，僅冀求短期 接受丁基原啡因治療概況
的抵癮，入監後以美沙冬暫時解決痛苦，卻無長遠維
持治療的打算
投資高額人力物力在監獄內執行美沙冬醫
療，除了達到提供人道醫療的效果以外，實
質上恐無法提升出監後銜接治療或維持治療
的比率。

接受Suboxone治療人數統計 接受Suboxone治療者戒斷原因統計

1月 2月 3月 4月 5月 6月 7月 8月 9月 10 11 12 總計
未治療人數 3 0 15 18 6 10 13 2 10 7 18 6 109
有治療人數 9 3 2 5 5 6 5 3 7 2 1 4 51 美沙冬戒斷 海洛英戒斷 接受治療人數
一級毒品案件
新收人數
12 3 17 23 11 16 18 5 17 9 19 10 160 31 20 51
接受治療比例 75% 100% 12% 22% 45% 38% 28% 60% 41% 22% 5% 40% 33%

9
 Suboxone治療天數統計 首次服用Suboxone劑量統計
人數

 以基隆監獄一級毒品收容人數及治療比例推估，新
入監一級毒品犯約有3成應接受戒斷治療，其中2成
係因美沙冬戒斷，1成約海洛因戒斷。全國去年新
入監一級毒品犯約4775人，推估有近1500名受刑人 毒品施用者治療與司法現況
之戒斷，並未得到妥適醫療
 基於人道立場，監所納入健保後，理應具備提供戒
癮藥物及治療之能力
 宜保留監所公醫制度及經費，以照顧經濟困難之收
容人

10
基隆醫院美沙冬新收及在案人數 本院美沙冬病人減少了，去哪了？
年度 當年度新收人數 當年平均在案人數  假設一：為求地利之便，改去其它醫院喝美沙冬
96 283 196  假設二：為求時間之便，改服用丁基原啡因
97 230 220  假設三：再犯，被判緩起訴至他院喝美沙冬
98 199 199  假設四：五年後再犯施用罪，被判觀察勒戒或戒治
99 267 244  假設五：五年內再犯施用罪，被判入監服刑
100 268 289  假設六：再犯毒品重罪，入監執行長刑期

101 237 325  假設七：新興毒品盛行，一級毒品施用人口減少中

102 120 293

103 131 243

104 27 (統計至5/7) 222

替代療法治療醫院 替代療法治療人數
 執行替代治療服務機構計106家醫院
僅提供丁基原啡因之機構計17家
2012.12 2013.12 2014.11 2014.12 2015.4
可提供美沙冬治療之機構計89家
美沙冬 11151 9642 8893 7530 8561

 衛星給藥點（或衛生所）計47家 丁基原啡因 79 91 189 112 235

僅提供丁基原啡因之機構計13家
總計 11230 9733 9082 7642 8796
可提供美沙冬治療之機構計34家

11
 本院美沙冬病人減少了，去哪了？ 基隆醫院緩起訴新收及在案人數
 假設一：為求地利之便，改去其它醫院喝美沙冬 年度 一級毒品緩起訴新收人數 一級毒品緩起訴在案人數

 假設二：為求時間之便，改服用丁基原啡因 96 0 0

 假設三：再犯施用罪，被判緩起訴至他院治療 97 22 26

 假設四：五年後再犯施用罪，被判觀察勒戒或戒治 98 15 13

 假設五：五年內再犯施用罪，被判入監服刑 99 30 26
 假設六：再犯毒品重罪，入監執行長刑期 100 70 63
 假設七：新興毒品盛行，一級毒品施用人口減少中 101 82 57

102 24 17

103 19 11

104 0 (統計至5/13) 6

歷年毒品案判處緩起訴人數及比例
毒品案 毒品案 一級毒品 二級毒品
歷年毒品案撤銷緩起訴處分人數
偵察終結人數 判緩起訴比例 緩起訴人數 緩起訴人數 一級撤緩 一級判緩 一級撤緩 二級撤緩 二級判緩 二級判緩
人數 人數 比例％ 人數 人數 比例
95 77609 0.2 108 11 94 4 5 80.0 ％ 0 5 0.0 ％

96 86425 1.2 931 51 95 2 7 28.6 ％ 1 2 50.0 ％

97 87499 2.0 1671 29 96 114 121 94.2 ％ 1 5 20.0 ％

98 73321 2.9 1716 381
97 323 353 91.5 ％ 22 24 91.7 ％
99 77936 3.6 1881 887
98 543 739 73.5 ％ 24 35 68.6 ％
100 77934 5.7 2370 2041
99 856 1271 67.3 ％ 124 146 84.9 ％
101 74056 5.3 1313 1990
100 1009 1615 62.5 ％ 457 661 69.1 ％
102 70150 3.9 794 1968
102 624 794 78.6 ％ 963 1968 48.9 ％
103 65075 4.0 668 1967

12
本院美沙冬病人減少了，去哪了？ 勒戒處所歷年收容人數
 假設一：為求地利之便，改去其它醫院喝美沙冬 一級毒品 二級毒品 一級毒品 二級毒品

 假設二：為求時間之便，改服用丁基原啡因
94 5845 7981 99 1807 7694
 假設三：再犯施用罪，被判緩起訴至他院喝美沙冬
 假設四：五年後再犯施用罪，被判觀察勒戒或戒治 95 4857 6160 100 1362 7203

 假設五：五年內再犯施用罪，被判入監服刑
96 4222 6737 101 946 6053
 假設六：再犯毒品重罪，入監執行長刑期
 假設七：新興毒品盛行，一級毒品施用人口減少中 97 3702 6608 102 814 5886

98 2642 5663 103 602 5376

戒治所歷年收容人數 新入監毒品受刑人數
年度 一級毒品 二級毒品 年度 一級毒品 二級毒品
年度 新入監毒品犯 一級毒品犯 比例 二級毒品犯 比例
總數 人數 人數
94 2318 843 99 823 647
98 12440 8685 69.8 3395 27.3

95 2040 790 100 587 507 99 11240 6291 55.9 4410 39.2

96 2468 1042 101 427 366 100 11474 5544 48.3 5205 45.4

101 10971 5083 46.3 5023 45.8

97 2098 1298 102 357 307

102 10343 4775 45.8 4789 45.9

98 1297 675 103 274 335

13
本院美沙冬病人減少了，去哪了？ 在監受刑毒品犯歷年人數
 假設一：為求地利之便，改去其它醫院喝美沙冬 毒品犯 全部在 佔比 毒品犯 全部在 佔比
監人數 監人數
 假設二：為求時間之便，改服用丁基原啡因 94 19775 48779 40.5％ 100 25257 57479 43.9％
 假設三：再犯施用罪，被判緩起訴至他院喝美沙冬
95 20671 51381 40.2％ 101 26326 58674 44.9％
 假設四：五年後再犯施用罪，被判觀察勒戒或戒治
 假設五：五年內再犯施用罪，被判入監服刑 96 14162 40461 35.0％ 102 26779 58565 45.7％
 假設六：再犯毒品重罪，入監執行長刑期
97 20933 52708 39.7％ 103 26683 57633 46.3％
 假設七：新興毒品盛行，一級毒品施用人口減少中
98 23636 55225 42.8％ 104.3 26589 56737 46.8％

99 24480 57088 42.9％

各類收容人98年-102年
本院美沙冬病人減少了，去哪了？ 出獄(所)後再犯經過時間
 假設一：為求地利之便，改去其它醫院喝美沙冬
 假設二：為求時間之便，改服用丁基原啡因
 假設三：再犯施用罪，被判緩起訴至他院喝美沙冬
 假設四：五年後再犯施用罪，被判觀察勒戒或戒治
 假設五：五年內再犯施用罪，被判入監服刑
 假設六：再犯毒品重罪，入監執行長刑期
 假設七：新興毒品盛行，一級毒品施用人口減少中？

14
 蔡維禎 醫師簡歷
目前職位：
1. 台北榮總 臨床毒物科 主治醫師（1989-）
2. 行政院衛生署暨台北榮總 毒藥物防治諮詢中心醫師（1987-）
3. 台北榮總 蘇澳分院 血液透析中心兼任醫師（2000-）
4. 台北市中心診所醫院兼任醫師（2001-）
學歷：
1. 中國醫藥大學 醫學系醫學士（1975-82）
2. 美國約翰霍普金斯大學 公衛學院 心理衛生碩士（1992-4）
曾任：
美國國家衛生研究院 NIH 國立藥物濫用研究所 NIDA 進修
美國約翰霍普金斯大學 行為藥理研究中心 BPRU 進修
國家衛生研究院 台灣成癮次專科臨床和研究訓練計畫執行委員會委員
教育部 全國反毒教育委員會委員
基督教晨曦會醫療顧問
中華民國減害學會理事
左營海軍總醫院醫師
台北長庚醫院內科醫師
中華民國環境職業醫學會理事
中華民國職業病醫學會監事
台北縣政府勞工安全衛生諮詢委員會委員
衛生署食品衛生處食品安全諮詢委員會委員
中央健康保險局台北分局醫療審核醫師

得獎：
美國國務院：韓福瑞獎學金（1992）
中華民國行政院：全國反毒有功人士（1999）
專科証書：
成癮次專科（2011）、內科（1989）、腎臟（1989）、急救加護（重症）（1991）
、環
境職業醫學（1995）
興趣及專長：
藥癮防治、中毒急救、內科疾病診治、腎臟疾病診治、環境職業疾病診治
1
毒藥物檢驗在藥物濫用病人處置之應用
Uses of Toxicological Examinations in Managing Drug Abuse

蔡維禎
Wei-Jen Tsai, M.D.,M.P.H.
台北榮民總醫院 臨床毒物與職業醫學科
Division of Clinical Toxicology and Occupational Medicine

台北榮總 毒藥物防治諮詢中心 中毒死亡個案

總個案數 死亡案數 死亡率

1994 3,582 116 3.24%
2005 4,190 100 2.39%
2014 2,933 56 1.91%
 台北榮民總醫院 臨床毒物與職業醫學科 實驗室分析項目 (2014/1~12)
項 目 院內人次 院外人次 小計人次
一般藥物篩驗 尿液鹼性類藥物篩檢 630 251 881
尿液苯二氮平類篩檢 464 540 1,004
安眠鎮靜劑 尿液巴比妥酸鹽類定性 68 5 73
尿液安眠藥確認BZD(LC/MSMS) 0 106 106
尿液藥物濫用篩檢(6項) 50 33 83
尿液嗎啡篩檢 464 490 954
尿液安非他命篩檢 510 4,294 4,804
尿液大麻篩檢 158 125 283
尿液天使塵篩檢 149 84 233 8,777/10,039 =
尿液古柯鹼篩檢 155 4 159 87.4%
藥物
尿液愷他命 (Ketamine) 試驗 11 84 95
濫用物質
尿液甲苯及其代謝物定量測試 16 1 17
毛髮安非他命確認 10 13 23
毛髮鴉片確認 2 0 2
毛髮大麻確認 2 13 15
毛髮天使塵確認 0 13 13
毛髮愷他命 (Ketamine) 確認 9 13 22
毒品定性分析 0 10 10
中藥添加西藥分析 14 0 14 16/10,039 =
Drug screen 2 0 2 0.2%
尿液巴拉刈定性測試 13 0 13
巴拉刈 Paraquat 尿液巴拉刈定量測試 43 45 88
血液巴拉刈定量測試 18 107 125 681/10,039 =
農藥
有機磷/氨基甲酸 6.8%
乙醯膽鹼酵素（紅血球及血漿）定量 187 266 453
鹽
殺鼠劑 殺鼠劑 0 2 2
Thiocyanate定量測試 3 56 59
氰化物 (cyanide) 定量測試 3 3 6
血液甲醇、乙醇定量測試 69 428 497 565/10,039 =
化學品
special substance analysis 3 1 0 1 5.6%
塑化劑代謝物 0 1 1
pH 1 0 1
合計 3,052 6,987 10,039

Considerations of Using Toxicological Testing in Clinical

Practice: Diagnosing, Screening, or Monitoring

 What to be Tested - Toxin Concerns

 Whom to be Tested - Subject Concerns
 What Sample? When to Collect?
 How to Test – (Methods) Facility/Technical Concerns
– Where
– Tools
 Time Concerns
 Cost Concerns
 Limitations / Difficulties / Pitfalls
 Principles in Managing Acute Poisonings
中毒病患之處理原則

Stabilization

Diagnosis (確定毒藥物之方法、線索)
─ History 暴露史(現場環境…)、病史
─ Physical Exams (身體症狀),
─ Lab: Routine / Toxicology
─ Consultation

Treatments
─ Decontamination (Lavage, Absorbents,Cathartics)
─ Enhance Elimination
─ Antidotes
─ Supportive Treatment

Common Toxic Syndromes

Toxidromes S/S Possible Toxins

Cholinergic
Acetylcholine,
Muscarinic Diarrhea, Urination, Miosis,
Organophosphates, Carbamates,
Bronchospasm, Bradycardia, Emesis,
(DUMB BELS) Betelnut, Mushrooms,
Lacrimation, Salivation
Pilocapine…
Tachycardia, Hypertension, Fasiculation,
Nicotinic Paralysis
Nicotine, Organophosphates

Dry Mouth, Fever, Tachycardia,

Belladona Alkaloids (Atropine,
Anticholinergic Hypertension, Mydriasis, dysuria,
Scopolamine), Datura,
Delirium, Seizure
Fever, Tachycardia, Hypertension, Amphetamines, Ephedrine,
Sympathomimetic Mydriasis, Delirium, Seizure, Cocaine, MDMA, Caffeine,
Diaphoresis Aminophylline
Coma, Resp. Failure, Miosis, Needle
Narcotic Marks
Heroin, Opiates, Opioids

Tachycardia, Hypertension, Mydriasis, Opiates, Opioids, Sedativs,

Withdrawal Delirium, Seizure, Diaphoresis Hypnotics, Ethanol
 系統性毒藥物分析

欲偵測物質 類別 萃取 (純化) 檢測
GC,
GC-MS,
有機溶劑、氰化物… 揮發性物質 蒸氣蒸餾或微量擴散法
LC-MS,
GC / LC-MS-MS
AA
鉛、汞、砷、鎘… 重金屬 灰化法…
ICP-MS

氯、溴、碘… 陰離子 透析或離子交換法 Colometry

TLC
HPLC
中西藥 有機物 有機溶劑萃取(酸性,鹼性)
GC-MS
GC / LC-MS-MS

…… ……. …………… …………

毒物檢驗基本步驟

血清、全血、尿液、嘔吐物、CSF、毛髮、
生物檢體 組織
檢體
藥品 錠劑、藥丸、膠囊、粉末、液體
Samples
蔬果、穀類、堅果類、魚肉、清涼飲料、
食物 酒、牛奶

前處理 濃縮、萃取 (SPE: Solid Phase Extraction; LL: Liquid/Liquid

Treatment Phase Extraction ) 、 呈色、衍生化

分離 液相層析儀 LC、氣相層析儀 GC、氣相-液相層析儀 60*C

1 2 3 4

Seperation GLC、毛細管電泳 EC、感應耦合電漿ICP

偵測器 紫外光 UV、光二極體陣列、螢光、折射率RI、火燄離 40 *C 1 2 3

4
子FID、火焰光度檢出器FPD、電子捕獲ECD、脈衝式
Detector 火焰光度PFPD、質譜MS、串連質譜MS/MS
20 *C 1 2
3
數據記錄 4

Recorder 0 2 4 6 8 10 12
(min)
 台北榮民總醫院 臨床毒物與職業醫學科
實驗室主要儀器設備

設備名稱 數量 (台)
紫外光/可見光光譜儀 (UV/VIR) 2
自動酵素免疫分析儀 1
高效液相層析儀 (HPLC-Photodiode arry ĉ Fluorescence ) 1
氣相層析質譜儀 (GC/MS) 3
氣相層析質譜儀 (GC/MS-EI / CI) 1
頂空自動進樣器-氣相層析儀 (CTC-GC-FID/FPD ĉ EPC) 1
氣相層析串聯質譜儀 (GC-MS MS) 1
液相層析串聯質譜儀 (LC-MS MS) 1
感應偶合電漿質譜儀 (ICP-MS) 1
火焰/石墨式原子吸收光譜儀 (AA) 1
檢體萃取前處理機 3
微波消化儀 1
微量分注器-多功能微盤分析 1
真空減壓濃縮裝置 1
吹氮氣試管濃縮裝置 3

毒藥物動力學
中毒時，體內濃度變化 / 對身體影響 / 檢驗、治療之考量

Toxin Concerns Patient Concerns (Susceptibilities)

 開始  毒性  吸收 A  體質 (種、屬、族群、年紀、性別、營
養、原本疾病)
作用 時間決定於  劑量  分布 D
 顛峰  其他毒藥物相互作用(體內外環境)
 劑型  代謝 M
 持續  酵素活性誘發或抑制 (耐受力)
 時間  排泄 E
 途徑
環境偵測

空氣
呼吸道 血液 標的器官 症狀/疾病
水 皮膚
食物 消化道 組織(脂肪, 骨骼)

血液, 組織液
生物偵測

尿液
呼氣
汗 (貼布), 唾液, 乳汁, 精液, 糞便
毛髮, 指甲
脂肪, 骨頭, 牙齒
 毒藥物檢測時檢體選擇之優缺點
檢體 優點 缺點 應用
X 侵入性
最正確反應外在暴露量
X 需嚴格的儲存條件
血液 最可能出現外來物之生物
X 分析前處理步驟繁複
定量
檢體
X 僅能反應較短期之暴露

X 單次樣本變異性大
非侵入性
X 長期完整樣本收集有困難
尿液 簡單
X 標準化參數(肌酐酸、比重、酸鹼值、滲透壓)之變異
定性
經濃縮較易檢測
與欲測定物的變異程度不一

X 僅能偵測體內半衰期較短之物質
非侵入性
X 終端呼氣(end-exhaled air)與混合呼氣(mlxed-
呼出氣體 簡易
exhaled air)收集方式之代表意義不同
半定量
重覆測試容易
X 異常肺功能者無法反應真實暴露

非侵入性 X 分泌量少、不穩定
唾液 簡易 X 成分易隨分泌速率、個人因素而變 定性
分析上介質效應較小 X 樣本取得不易標準化

非侵入性
毛髮/指甲
可反應長期之暴露
X 檢體之清洗尚未能排除外因污染 半定量

如何從大海撈針?

Common Drugs Included on Most Toxicologic Screens

Categories Examples
Alcohols Ethanol, methanol. isopropanol, acetone
Analgesics Salicylates, acetaminophen
Amitriptyline, nortriptyline, doxepin, imipramine, desipramine, trazodone, amoxapine,
Anti-depressants
maprotiline, fluoxetine
Anti-epileptics 藥物中毒常用之檢驗:
Phenytoin, carbamazepine, primadone, phenobarbital
Anti-histamines 1. 鹼性藥物篩驗
Diphenhydramine, chlorpheniramine,
Basicbrompheniramine,
doxylamine, pyrilamine, methyprylene
Drug Screentripennelamine, trihexyphenidyl,
Anti-psychotics 2. 藥物濫用篩驗 Drugs of Abuse
Trifluoperazine, perphenazine, prochlorperazine, Screen
chlorpromazine
Barbiturates/Sedativ Amobarbital, secobarbital, pentobarbital, butalbital, butabarbital, phenobarbitall
es
3. 治療藥物監測 TDM Therapeutic
glutethimide. ethychlorvynol, methaqualone
Drug Monitoring
Benzodiazepines Chlordiazepoxide, diazepam, alprazolam, temazepam
Cardiovascular
Lidocaine, propranololl metoprolol, quinidine, procainamide, verapamil
Drugs
Heroin, morphine, codeine, oxycodone, hydrocodone, hydromorphone, meperidine,
Narcotics 鹼性藥物篩驗 A 藥物濫用篩驗
pentazocine, propoxyphene
Amphetamine, methamphetamine, phenylpropanolamine, ephedrine, MDA and MDMA
Stimulants B C
(other phenylethylamines), cocaine, phencyclidine
Others E nicotine,Doral hypoglycemics,
Theophylline, caffeine, TDM strychnine
 一般檢查與毒藥物檢測之使用時機
Types of Medical and Toxicologic Test Situations

使用時機 品質訴求 臨床案例項

目的 毒藥物檢測
Medical 用途 Quality 目Clinical 檢測物質
Purposes Toxicologic Examples
Settings Required Examples

診斷、評估嚴重度 Specific S/S 鹼性藥物篩驗 Acetaminophen, Salicylate

診斷依據 找出問題 特異性
to Diagnose Severity or + 藥物濫用篩驗 Theophylline, Iron
Diagnostic Sort, Categorize Specificity
Monitor Course CK-MB TDM Methanol, Ethylene Glycol

評估療效與病程監控 All in the above.

血壓,心跳,
•as Criteria for Therapy, Lithium, Digoxin, Anti-
體溫 鹼性藥物篩驗
濃度監控 度量嚴重程度 •Assess Effectiveness of 精準性 Epileptics, etc
BP,TPR 藥物濫用篩驗
Monitoring Measure change Therapy; Precision CO-Hb,
+ TDM
•Monitor Clinical Fe, Pb, Hg, As,
Specific S/S
Course ChE (Ops, Carbamate)

-DDx : Disease or Drug?

鹼性藥物篩驗 (Functional or
藥物濫用篩驗 Amphetamine Psychosis).
(Employee Drug Abuse
其他用途 Testing, Drug Facilitated -R/O: Unlikely Cause
Specific S/S
篩檢管控 發現及監視問題 Situations in Which 敏感性 Sexual Assault) ("Rule-out" Value).
+
Screening Find Toxicologic Screens Sensitivity
PKU
have Utility TDM - Preventive: Pre- During,
特定毒物篩驗
Toxicology Screen - Confirmation: Document
(Hazard Testing) The Working Dx (Post
Factum).

鹼性藥物篩驗 A 藥物濫用篩驗

B C

D TDM

鹼性藥物篩檢 Basic Drug Screen

 檢驗單位：台北榮總 內科部 臨床毒物與職業醫學科

 檢體：50mL尿液，於5℃儲存
 報告時效：報告兩週
 費用：健保給付 、自費
 分析方法：Toxi-Lab-A/GC-MS (Previous:Toxi-Lab-A/HPLC/Remedi/UVD)

 應用：篩檢約四百種鹼性藥物，含常用藥物、濫用物質、少數農藥
 神志不清或昏迷者，請加做Benzodiazepines Screen、Barbiturate
Screen；症狀懷疑濫用藥物，請加做Drug Abuse Screen
 Basic Drug Screen: 389 Detectable Compounds (review-2011)
台北榮總毒物科

藥物類別 總數 項目
Sedatives, Hypnotics, Anticonvulsants,
神經系統類 163
Antipsychotics, Antidepressants, etc.
濫用藥物類 39 Stimulants, Hallucinogens (Pub Drugs), etc.
ACEIs, ARBs, Beta Blockers, CCBs, Anti-
心臟血管系統類 52
arrhythmics, Fibrates, etc.
呼吸系統類 38 Antitussives, Mucolytics, Antihistamines, etc.
Acetaminophen, NSAIDs, Tramadol,
止痛類 45
Methadone, Heroin, 6AM, Codeine, etc.
Caffeine, Antibiotics, Androsterone, Bisacodyl,
其他類 32 H2-Blockers, Quinine, Colchicine, Strychinine,
Eugenol, Menthol, etc.
Organophosphates, Carbamates, Pyrethroids,
其他類化學物質 20
Caprolactam, Triclosan, Sibutramine, etc.

Abused Substances Detectable in Basic Drug Screen, Taipei VGH

 Sedative/Hypnotics:
– Benzodiazepines: alprazolam, bromazepam, brotizolam, camazepam, chlordiazepoxide, clobazam,
clonazepam, clorazepate, clotiazepam, demoxepam, diazepam, estazolam, flunitrazepam,
flurazepam, halazepam, ketazolam, loprazolam, lorazepam, lormetrazepam, medazepam,
midazolam, nimetazepam, nitrazepam, nordiazepam, oxazepam, oxazolam, temazepam, tetrazepam,
benzodiazepine's metabolite (28+)
– Barbiturates: allobarbital, amobarbital, aprobabital, barbital, butabarbital, mephobarbital,
methohexital, pentobarbital, phenobarbital, secobarbital, thiopental (11+)
– Others: glutethimide, methaqualone, meprobamate, propofol, zolpidem, zolpiclone, zaleplon
 Narcotics:
– codeine, morphine, heroin, cocaine, ecogonine methyl ester
 Stimulants/ Hallucinogens:
– Phenyl-ethylamines:
 amphetamine, methamphetamine, cathinone (Khat), synthetic cathinone (mephedrone)
 Pharmaceuticals (for ADD/ADHD): fenethylline, methylphenidate
 Anorectics: chlorphentermine, fencamfamine, mazindol, phentermine, phenmetrazine, phenylpropanolamine (PPA), diethylpropion,
phendimetrazine, fenfluramine, clobenzorex, fenproporex, mefenorex
 Hallucinogens: MDEA (3,4-methylenedioxy-N-ethylamphetamine), MDMA (3,4-methylenedioxymethamphetamine), MDA (3,4-
methylenedioxyamphetamine), MMDA (3-methoxy-4,5-methylenedioxyamphetamine), PMMA (p-methoxymethamphetamine), PMA
(p-methoxyamphetamine), DOB (4-bromo-2,5-dimethoxyamphetamine), 2C-C (2,5-dimethoxy-4-chlorophenethylamine), 2C-I (2,5-
dimethoxy-4-iodophenethylamine), 2C-T-2 (2,5-dimethoxy-4-ethlthiophenethylamine), 2C-T-7 (2,5-dimethoxy-4-
propylthiophenethylamine)
– Indoyl-alkylamines (Tryptamines):
 Hallucinogens: 5-Meo-DIPT (N,N-diisopropyl-5-methoxy-tryptamine), 5-Meo-DMT (5-methoxy-N,N-
dimethyltryptamine), AMT (α-methyltryptamine), DMT (N,N-methyltryptamine), bufotenine (5-HO-DMT), DBT(N,N-
dibutyltryptamine), DET (N,N-diethyltryptamine), DIPT (diisopropyl-tryptamine), DPT (N,N-dipropyltryptamine)
– Piperidines: Hallucinogens: ketamine, phencyclidine, atropine, scopolamine
– Others: isometheptene
 台北榮總 內科部 臨床毒物與職業醫學科
毒藥物檢驗 檢驗流程

 確認檢驗項目 → 開立檢驗單

 遵守品質管控*Chain of Custody收集檢體 → 儲存 (*藥物濫用檢驗)

 進行檢驗流程：

標號 → 前處理 → 分離 → 偵測 → 數據分析紀錄 → 初步報告

 報告：

初步報告 → 實驗室組長核簽 → 毒物科醫師核簽 → 寄發報告

 檢驗流程有問題、新發現或醫師認為與臨床有出入立即進行討論

鹼性藥物篩驗 A 藥物濫用篩驗

B C

D TDM

藥物濫用篩檢 Drugs of Abuse Screen

 檢驗單位：台北榮總 內科部 臨床毒物與職業醫學科

 檢體：50 mL尿液，於5℃儲存

 報告時效：陰性1~2週，陽性1~3週

 費用：自費

 分析方法：EIA, GC-MS, LC-MS-MS, …

 應用：可篩檢約十多種濫用物質

 症狀懷疑不明濫用藥物，可於毒物科醫師門診討論並開立檢驗單
 濫用藥物篩驗 Drugs of Abuse Screen
台北榮總毒物科
類別 總數 項目
Amphetamines Screen 4 Amphetamine, Methamphetamine, MDMA, MDA.
苯二氮平類 (alprazolam, chlordiazepoxide, clonazepam, diazepam, 
estazolam, FM2, lorazepam,  midazolam, nitrazepam, nimetazepam, 
Benzodiazepines Screen 22 + 5 oxazepam, oxazolam, triazolam, fludiazepam, flurazepam, 。 非苯二
氮平類：clozapine, trazodone , zaleplon , zolpidem , zopiclone

Barbiturates Screen 3 Phenobarbital, Amobarbital, Secobabital, …

Cannabinoids Screen 1 Δ-THC
Cocaine Screen 1 Cocaine
Ketamine 1 Ketamine, nor-Ketamine
Methaqualone 1 Methaqualone
Opiates Screen (非Opioids) 3? Morphine, 6-Acetyl morphine, Codeine, etc
Phencyclidine Screen 1 Phencyclidine
Basic Drug Screen中之濫用藥 Some Benzodiazepines, Barbiturates, Stimulants,
39 Hallucinogens (Pub Drugs), etc.
物類藥物
Special Request 藥物檢測 Some Benzodiazepines, Hallucinogens (Pub Drugs), etc.
GHB, GBL
Under Developing K2
Synthetic Cathinones

鹼性藥物篩驗 A 藥物濫用篩驗

B C

D TDM

苯二氮平類鎮定安眠劑尿液檢驗 Benzodiazepine Screen

 檢驗單位：台北榮總 內科部 臨床毒物與職業醫學科

 檢體：50 mL尿液，於5℃儲存
 報告時效：陰性1~2週，陽性1~3週
 費用：自費
 分析方法：
1. 初篩: EIA (無法分辨哪一種)
2. 確認: LC-MS-MS ，本實驗室可檢出藥物，
 苯二氮平類，22種 : alprazolam, bromazepam, brotizolam, clobazam, chlordiazepoxide, 
clonazepam, diazepam, estazolam, flunitrazepam(FM2), lormetazepam, lorazepam,  
midazolam, nitrazepam, nimetazepam, nordiazepam,   oxazepam, oxazolam, prazepam, 
triazolam, fludiazepam, flurazepam, temazepam, 及其代謝物
 非苯二氮平類，5種：clozapine, trazodone , zaleplon , zolpidem , zopiclone
3. Sensitivity 優於 Basic Drug Screen
4. Special Request: 懷疑不明藥物，可於毒物科醫師門診討論並開立檢驗單
 Comparison of
Drugs of Abuse Screen (DAS) and Comprehensive Drug Screen (CDS, e.g., Basic Drug Screen)

DAS CDS

Availability All days, all shifts 6 days/wk, day shift

Sample Used Urine, 30~50 ml Urine, 30~50 ml

Methods EIA, TLC, GC-MS, GC-

EIA MS-MS, LC-MS-MS, etc
Stat: 45 min (ER Lab)
Time to Negative Results 6 hrs or days
Routine: 2 hrs (Tox Lab)
45 min for
Amphetamines, Opiates,
Time to Positive Results Cocaine, BZDs, Ethanol 6 hrs or days
2-8 h for others

Total Drugs Screened 50+ illicit +

Common 8 illicit Pharmaceuticals
 Comprehensive Urine Drug Screen: an Example
 A two part assay which screens for up to 700 pharmaceutical and illicit
compounds, to give clinicians the broadest information as to drugs present in the
patient’s urine.
 The initial part: screens the urine for some of the most commonly used / abused
drugs using EIA, etc. (Basic Drug Screen – Taipei VGH)
 The second part: GC/MS or LC-MS-MS screen incorporating Deconvoluting
Reporting Software (DRS) which will scan and identify up to 700 compounds.
 Comprehensive Urine Drug Screen: Test Code: 4784
 Tests for, but is not limited to the following drugs:
 *Acetaminophen, Narcotics/*Opiates,*Phencyclidine (PCP), Sympathomimetic Amines:
 Codeine, Phenothiazines,Antihistamines: Chlorpheniramine,Diphenhydramine,Dextromethorphan,
Phenytoin, *Methamphetamine,*Amphetamine,Hydrocodone,Procainamide/NAPA, Ehedrine,
Doxylamine, Hydromorphone, Propranolol, Pseudoephedrine, Promethazine,Meperidine, Pyrilamine,
MDMA (Ecstasy), *Barbiturate, *Methadone, Quinidine/Quinine,
Phenylpropanolamine,*Benzodiazepines, Morphine, *Salicylates, *THC (Marijuana), Carbamazepine,
Oxycodone, Trazodone, *Cocaine, Pentazocine, Tricyclic Antidepressants, *Ethanol,
Propoxyphene,Verapamil, Verapamil, Norpropoxyphene.
 *A Comprehensive Urine Drug Screen panel ordered STAT will test only for the asterisked
drugs above. The remaining drugs are tested and / or confirmed by GC/MS on a routine
basis only, Monday – Friday, 8am – 10pm, excluding holidays.

台北榮總 內科部
臨床毒物與職業醫學科
聯絡電話:
毒藥物諮詢中心：02-28757525 轉821 (24小時專線)
實驗室：02-28757525 轉802或803
位址：
台北榮民總醫院致德樓五樓
網址：
http://www.pcc.vghtpe.gov.tw
 台北榮民總醫院 臨床毒物與職業醫學科 實驗室分析項目
項 目 院內價格 院外價格 陰性報告時間 陽性報告時間
一般藥物篩驗 尿液鹼性類藥物篩檢 1,300 3,000 5~7工作天 5~7工作天
尿液苯二氮平類篩檢 416 420 1~3工作天 --
安眠鎮靜劑 尿液巴比妥酸鹽類定性 416 420 1~3工作天 --
尿液安眠藥確認BZD(LC/MSMS) 4,000 4,000 -- 10~15工作天
尿液藥物濫用篩檢(6項) 3,000 3,000 3~5工作天 5~7工作天
尿液嗎啡篩檢 325 -- 3~5工作天 5~7工作天
尿液安非他命篩檢 325 -- 3~5工作天 5~7工作天
尿液大麻篩檢 325 -- 3~5工作天 5~7工作天
尿液天使塵篩檢 325 -- 3~5工作天 5~7工作天
尿液古柯鹼篩檢 325 -- 3~5工作天 5~7工作天
藥物
尿液愷他命 (Ketamine) 試驗 1,500 1,500 3~5工作天 5~7工作天
被濫用物質
尿液甲苯及其代謝物定量測試 2,890 2,890 -- 5~7工作天
毛髮藥物確認、安非他命、鴉片、大麻、K他命 每項3,000 3,000 -- 10~15工作天
尿液藥物濫用篩驗, 3種藥物, 自費 2,000
尿液藥物濫用篩驗, 5種藥物, 自費 2,500
尿液藥物濫用篩驗, 6種藥物, 自費 3,000
尿液藥物濫用篩驗, 4種藥物, 自費,含K他命 3,000
毒品定性分析 2,000 1,050 -- 10~15工作天
中藥添加西藥分析 3,000
Drug screen
尿液巴拉刈定性測試 65 -- 10 mins 10 mins
巴拉刈 Paraquat 尿液巴拉刈定量測試 351 500 -- 1~3工作天
農藥 血液巴拉刈定量測試 351 500 -- 1~3工作天
有機磷/氨基甲酸鹽 乙醯膽鹼酵素（紅血球及血漿）定量 468 500 -- 1~3工作天
殺鼠劑 殺鼠劑 4,000 4,000 -- 10~15工作天
Thiocyanate定量測試 325 450 --
氰化物 (cyanide) 定量測試 195(定性) 800(定量) --
血液甲醇、乙醇定量測試 429 600 -- 1~3工作天
化學品
special substance analysis 3 3,000 3,000 -- 10~15工作天
塑化劑代謝物 4,000 4,000 -- 10~15工作天
pH 65 -- -- 10 mins
Problems of Drug Abuse 
in Taiwan

Commonly Substances Seized in Taiwan, 1987~2013

6,869

3,981

Ministry of Justice, Taiwan

 Results of Urine Drug Testing in Taiwan. Data from All DOH Certified Labs: Pub Drugs
Food and Drug Administration, Department of Health (DOH), Taiwan

Pub Drugs, Cases 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
Mj 3 0 3 15 11 80 67 87 96 70 70 130 110
Cocaine 0 0 0 0 0 0 5 0 5 1 0 0 0
MDMA 1 149 987 3,899 1,660 1,630 1,006 1,445 608 633 396 392 504
MDA 0 0 0 152 53 2 10 47 39 13 3 31 2
MDEA 0 0 0 0 0 5 0 0 0 0 0 0 0
Ketamine (K) 0 0 0 47 22 299 540 994 1,363 2,409 4,438 7,388 11,616
MDMA + K 0 0 0 0 34 140 259 233 178 274 363 490 730
MDA + K 0 0 0 0 0 0 1 17 9 12 10 47 2
MDMA + Mj 0 0 0 0 0 8 23 6 2 12 5 5 4
MDMA + Am 0 0 10 80 41 183 48 59 49 113 99 105 57
MDA + Am 0 0 0 34 3 3 1 1 0 3 0 7 0
K + Am 0 0 0 0 19 23 36 31 119 197 605 1,172 1,160
K + Am + Mj 0 0 0 0 0 2 1 2 1 4 2 6 1
K + Am + MDMA 0 0 0 0 0 7 2 15 7 52 99 111 113
K + Mj 0 0 0 0 0 0 1 1 9 4 11 10 10
K+M 0 0 0 0 0 1 1 0 3 3 16 17 33
K + M + Codeine (Cod) 0 0 0 0 0 9 6 3 6 13 14 15 19
K + Am + M + Cod 0 0 0 0 0 3 6 2 7 14 36 37 35
PCP 0 0 0 0 0 0 1 0 0 0 0 0 0
PCP + MDMA 0 0 0 0 0 1 0 0 0 0 0 0 0
PCP + MDMA + K 0 0 0 0 0 1 0 0 0 0 0 0 0
MDEA + MDMA+ K 0 0 0 0 4 2 1 0 0 0 0 0 0
2CB + MDMA + K 0 0 0 0 0 8 9 14 3 0 1 1 1
2CB + K 0 0 0 0 0 0 29 1 0 0 0 0 0
PMMA 0 0 0 0 0 0 3 0 0 0 0 0 0
K + Rohypnol 0 0 0 0 0 0 1 1 0 0 0 0 0
K + Nimetazepam 0 0 0 0 0 0 0 0 2 4 1 0 0

Results of Pills/Powder Tested in Taiwan. Data from All MOHW Certified Labs
Food and Drug Administration, Ministry of Health and Welfare (MOHW), Taiwan

2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014/1 sum

2C-I + MDMA + K +Caffeine 0 0 0 0 0 0 7 0 0 0 0 7

MDPV + MDMA + K +Caffeine 0 0 0 0 0 0 0 0 0 10 0 10

MDPV + Meth + K + Caffeine 0 0 0 0 0 0 0 0 10 0 0 10

PCA + MDMA + Meth + Caffeine 0 0 0 0 0 4 7 0 0 0 0 11

PCA + 4FA + Meth + Caffeine 0 0 0 0 0 10 0 0 0 0 0 10

BZP + TFMPP + Meth + Caffeine 0 0 0 0 0 0 0 0 14 0 0 14

bk- MDMA(Methylone) + MDMA

0 0 0 0 0 0 0 0 0 8 0 8
+ Ketamine + Nimetazepam
MDPV,
Mephedrone﹑Methylone, ,
0 0 0 0 0 0 0 0 0 0 11 11
GHB, Nimetazepam, Ketamine,
Acetaminophen
PCA, Mephedrone, Ketamine,
MDMA, Amphetamine,
0 0 0 0 0 0 0 0 0 0 28 28
Methamphetamine,
Methylephedrine, Caffeine

Meth: Methamphetamine
 Simultaneous Determination of 40 Novel Psychoactive Stimulants in Urine
by Liquid Chromatography-High Resolution Mass Spectrometry and Library
Matching
Concheiro M, Castaneto M, Kronstrand R, Huestis MA
J Chromatogr A. 2015 Jun 5;1397:32-42. doi: 10.1016/j.chroma.2015.04.002. Epub 2015 Apr 8.

 The emergence of novel psychoactive substances is an ongoing challenge

for analytical toxicologists. Different analogs are continuously introduced in the market to
circumvent legislation and to enhance their pharmacological activity. Although detection of drugs
in blood indicates recent exposure and link intoxication to the causative agent, urine is still the
most preferred testing matrix in clinical and forensic settings.
 We developed a method for the simultaneous quantification of 8 piperazines, 4 designer
amphetamines and 28 synthetic cathinones and 4 metabolites, in urine by liquid chromatography
coupled to high-resolution mass spectrometry (LC-HRMS).
 Data were acquired in full scan and data dependent MS(2) mode. Compounds were quantified by
precursor ion exact mass, and confirmed by product ion spectra library matching, taking into
account product ions' exact mass and intensities. One-hundred μL urine was subjected to solid
phase cation exchange extraction (SOLA SCX). The chromatographic reverse-phase separation
was achieved with gradient mobile phase of 0.1% formic acid in water and in acetonitrile in 20min.
 The assay was linear from 2.5 or 5 to 500μg/L. Imprecision (n=15) was <15.4%, and accuracy
(n=15) 84.2-118.5%. Extraction efficiency was 51.2-111.2%, process efficiency 57.7-104.9% and
matrix effect ranged from -41.9% to 238.5% (CV<23.3%, except MDBZP CV<34%). Authentic
urine specimens (n=62) were analyzed with the method that provides a comprehensive
confirmation for 40 new stimulant drugs with specificity and sensitivity.

衛福部目前認證檢驗項目
 尿液
– 海洛因、嗎啡代謝物
– 安非他命類藥物
– MDMA/MDA (搖頭丸)
– 愷他命 (Ketamine)代謝物
– 大麻代謝物
 花蓮民宿老闆藥物性侵案件 (2010-6)
檢驗結果:
1st尿液篩驗: 陰性 (<200ug/L) → 蛋糕: Zolpidem → 2nd尿液篩驗: Zolpidem (Stilnox)

G水 GHB γ-Hydroxybutyric acid: Use/Abuse/DFSA

Use: GHB powder dissolved in water, mild salty, Rapidly absorbed.

Control: 第二級毒品
Dose: Recreational 1-3g, Combined Use with MDMA.
Onset: 10-20 minutes
Duration of Action: 1-2 hrs → next 1-2 hrs (subtle effects)
Sport Drink
Effects: Similar to Alcohol (Much Rapid and Profound)
– Low Dose: Relaxing, Euphoric, Slow Motion
– High Dose:
 Dizziness, Nausea, Slurring Speech, Drunken Apperance
 Uncontrolled Movement Responding to Rave Music

Metabolism & Excretion: H ½ : 3 min.

Limited Time of Lab Detection:
 Blood: 4~ 8 hrs
 urine: 8~12 hrs
Endogenous GHB:
 Plasma  4 mg/L

 Urine  0.1 mg/L

 PMMA, Para-Methoxy-Meth-Amphetamine

Case:
• 16 y/o male, ingested 2 pills of PMMA

• Coma, Seizure within 1 hour

• Hypotension, Hypoglycemia

• Transferrred to our ER after resuscitation

• Died of profound hypotension eventually

檢驗結果: PMMA (第三級毒品)

基隆警方指出，當時十五歲陳姓少年吃兩顆半、十六歲林姓少年吃兩顆
後中毒，陳送醫時已死亡，林轉送北榮時昏迷休克、不斷抽筋，血壓、
血糖偏低，急救後仍因肝腎衰竭死亡。

Considerations of Using Toxicological Testing in Clinical

Practice: Diagnosing, Screening, or Monitoring

 What to be Tested? (Toxin, Metabolites, Pharmacokinetics)

 Who needs to be Tested? (Patients, Employees)
 When to Collect Sample? (to know what in the past hrs, days, wks, mon.)
 What Sample Used ? (Urine, Saliva, Blood, Hair, Drugs, Foods)
 How to Test – (Methods/Technical Concerns)
– Where
– Tools
 How long or important will be the result?
 Cost Concerns
 Limitations, Difficulties, or Pitfalls
 台北榮總 內科部
臨床毒物與職業醫學科
聯絡電話:
毒藥物諮詢中心：02-28757525 轉821 (24小時專線)
實驗室：02-28757525 轉802或803
位址：
台北榮民總醫院致德樓五樓
網址：
http://www.pcc.vghtpe.gov.tw

謝謝聆聽，敬請指教！
1
 蒙恩醫師簡歷
現職：
 三軍總醫院門診手術室主任
 三軍總醫院外科部泌尿外科主治醫師
 國防醫學院醫學系外科學系專任助理教授
 台灣泌尿醫學會尿路動力學暨婦女泌尿學委員會委員

學歷：
 國防醫學院醫學系醫學士
 英國牛津大學藥理學博士

經歷：
 三軍總醫院泌尿外科主治醫師 (2003 年 8 月-2004 年 7 月)
兼 國軍基隆醫院外科主治醫師
 三軍總醫院泌尿外科專任主治醫師 (2003 年 8 月起)

專長：
 婦女泌尿疾病、尿失禁、排尿功能障礙、下泌尿道神經生理及病理學
1
 How to treat ketamine
cystitis?

蒙恩 醫師
三軍總醫院 泌尿外科
23, May. 2015

Case presentation
• 23-year-old man
• Frequency, urgency, nocturia, incomplete
voiding, hematuria and bladder pain for a
year
• Ketamine abuse for 4 years (6-10 g/day)
• Not combine using other drugs
• IPSS: 35; OABSS: 10; VAS: 10
• IC symptom index: 20, problem index: 16

1
 BEFORE TREATMENT

FD: 30 mL FBC: 75 mL ; small bladder

capacity and detrusor overactivity

2
 Ketamine associated cytitis

Ketamine and LUTS

• Large case studies in HK and UK had
revealed that nearly 92% of the chronic
ketamine abusers displayed urinary
symptoms
• Peak age: 16-35 years
• No gender bias

Chan YC. J Med Toxicol (2012) 8: 267-70.

Kalsi SS, Wood DM, Dargan PI. Emerg Health Threats J (2011) 4: 7107
Middela, S., and Pearce, I. (2011). Int J Clin Pract 65, 27-30

3
Ketamine related urinary tract symptoms

Frequency

Bladder
Urgency
pain

Urge
Dysuria
incontinence

Hematuria Nocturia

Make the diagnosis

History of ketamine abuse
• Duration?
• Dose? Combine with other drugs?
• Still using?
Lab
• Hematuria/pyuria?
• Liver and renal function
Imaging studies: ultrasound, RP, VCUG…

Urodynamic study

Cystoscopy + bladder biopsy

4
Ultrasound of kidney

5
VU reflux

Small bladder
capacity

6
 Chen, J. L., et al. (2013). Am J Emerg Med 31, 1153 e3-5

Ketamine bladder

Hyper-
Contracted
sensitive
（攣縮）
(過度敏感）

7
 Urodynamic characteristics

Decreased
Detrusor
bladder
overactivity
compliance

High maximal
Small bladder
urethral closure
capacity
pressure

Chu, P. S., et al. (2008). BJU Int 102, 1616-22

Tsai, T. H., et al. (2009). Int J Urol 16, 826-9

Sustained bladder contraction

8
 Huang, P.-W., et al. (2014) LUTS: Lower Urinary Tract Symptoms 6(2), 98-102.

Increased maximal urethral closure

pressure
MUCP>90 cmH2O: 70%

9
 Functional bladder capacity

FBC<150 mL: 71%

Long-term use of ketamine decreases the

maximal bladder capacity

10
Large-dose use of ketamine decreases the
maximal bladder capacity

Cystoscopy findings

Marked and diffuse inflammation

Neovascularization and petechia

Denuded epithelium

Hemorrhagic cystitis

Ulcerative cystitis

11
Multiple petechial hemorrhages and
neovascularization

Eosinophil infiltration in a human

ketmaine bladder

24

12
 Pathophysiology?

To be established

Pathological features of KC
Urothelium aptosis

Eosinophil infiltration

Loss of cell-cell junction

Nerve hyperplasia

Generalized inflammation

Mimics carcinoma in situ

13
 What we’ve known from ketamine-
treated animal model
Up-regulations of purinergic signaling

Enhancing interstitial fibrosis and accelerating

macrophages infiltration

Up-regulations of COX-2 and iNOS and eNOS

expressions

Decrease in the cholinergic neurons

Hypersensitivity to ketamine?
• Serum IgE was significantly higher in the 20
patients with ketamine cystitis
• Serum IgE and the severity of eosinophil
infiltration were associated with bladder pain
severity and small maximal bladder capacity
• Bladder biopsy: submucosal fibrinoid necrosis of
arterioles
• Type III hypersensitivity immune response might
be involved in pathogenesis of ketamine cystitis

Jhang, J. F., Hsu, Y. H., Jiang, Y. H., et al. (2014). J Urol 192, 1249-1256.

14
 病因

膀胱纖
慢性發炎
維化

• 過敏造成的免疫反應
• 代謝物的直接毒性

Treatment

15
 TREATMENT
Ketamine withdrawal

NSAIDS?

Anticholinergic therapy?

Steroids?

Hydrodistention

Intravesical instillation of Hyaluronic acid

Intravesical botulinum toxin injection?

Augmentation cystoplasty

Ketamine withdrawal

• Ketamine withdrawal is the first step and

final goal for resolution of the symptoms
• Should based on a case-by-case basis,
with the involvement of a multidisciplinary
team (urologists, social workers,
psychiatrists, dedicated nurses and family
members)

Shahani, R., Streutker, C., Dickson, B., et al. (2007). Urology 69, 810-812.
Tam, Y.-H., Ng, C.-F., Pang, K. K.-Y., et al. (2014). BJU International 114, 754-760.
Tsai, T. H., Cha, T. L., Lin, C. M., et al. (2009). Int J Urol 16, 826-829.

16
2013-11 Started withdrawal

21 Y/O female, 72 months, 1-5 gm/day

2015-4 1.5 yr after withdrawal

21 Y/O female, 72 months, 1-5 gm/day

17
 Anti-inflammatory agents
• Anti-inflammatory agents including both
non-steroidal anti-inflammatory drugs and
COX-II inhibitors are commonly used in
the initial management of these patients

Shahani, R., Streutker, C., Dickson, B., et al. (2007). Urology 69, 810-812.
Tam, Y.-H., Ng, C.-F., Pang, K. K.-Y., et al. (2014). BJU International 114, 754-760.
Tsai, T. H., Cha, T. L., Lin, C. M., et al. (2009). Int J Urol 16, 826-829.

Repair GAG layer

• Damage to the glycosaminoglycan layer
was one of the proposed pathophysiology
of ketamine associated cystitis
• Oral pentosan polysulfate and intravesical
instillation of hyaluronic acid (cystitat)
could improve urinary symptoms of these
patients

Tsai TH, Cha TL, Lin CM, et al. Int J Urol. 2009. 16(10):826-9

18
 The 23-year-old man…

2013.7 POST HA INSTILLATION

IPSS: V/S: 7/12, OABSS: 4, VAS: 2

FBC: 95 mL

19
 2013.11 POST BOTOX INJECTION

IPSS: V/S: 7/6, OABSS: 4, VAS: 1

FBC: 109 mL

Hyaluronic acid instillation for

treatment of KC

20
IPSS

21
 O'leary-Sant interstitial
cystitis symptom index
and problem index

Augmentation cystoplasty
• For patients with contracted bladder due to
irreversible fibrotic changes of bladder
secondary to prolonged inflammation
• Preoperative detailed counseling is needed
• Recirculation of ketamine metabolites by the
intestine used in augmentation cystoplasty→
very high concentration of circulating ketamine
→ serious complications (e.g. renal failure,
convulsion etc.)

Ng, C. F., Chiu, P. K., Li, M. L., et al. (2013). Int Urol Nephrol.

22
 Before cystoplasty

25 Y/O male, 36 months, 3 gm/day

3 months after cystoplasty

23
 TAKE HOME MESSAGE

年輕人患嚴重刺激性下泌尿道症狀，又曾有K他命濫用史且沒
有任何其他病因，應是患有K他命膀胱炎

尿路動力學檢查及膀胱鏡檢查可以幫助確定診斷

尿路動力學檢查可見過度敏感和攣縮的膀胱，亦會見尿道壓力
過高

目前停止K他命濫用是唯一有效的治療方法。 玻尿酸膀胱灌注
和肉毒桿菌注射膀胱可能有助於改善症狀。若膀胱嚴重攣縮，
可能需要施行膀胱擴大手術。

24