Download How should I prescribe methadone for detoxification

Heroin detoxification with buprenorphine on an inpatient psychiatric unit .
Journal of Substance Abuse Treatment , Volume 23 , Issue 3 , Pages 163 - 169 B .
DiPaula , R . Schwartz , I . Montoya , D . Barrett , C . Tang
The purpose of this open-label, uncontrolled study was to evaluate the
feasibility of administering off-label buprenorphine in combination with
ancillary medications for inpatient short-term detoxification of heroindependent patients at a psychiatric facility. A sample of 20 heroin-dependent
patients admitted to an urban psychiatric hospital was administered
buprenorphine 6, 4, and 2 mg/day during the first, second, and third day of
detoxification, respectively, and then observed during the fourth and fifth day.
Eighty-five percent of the subjects abused other substances, 75% reported
cocaine abuse/dependence, 75% had comorbid mood disorders. All subjects
completed the medication phase of the study. No clinically significant adverse
events were reported. There was a significant decrease in the Clinical
Investigation Narcotic Assessment (CINA) total score between baseline and
days 2 through 5. The results suggest that buprenorphine is well tolerated and
may be beneficial for medically supervised short-term withdrawal from heroin
for hospitalized psychiatric patients.
***************************************************************************
*****************************************
Opioid dependence - Management
How should I prescribe buprenorphine for someone on street
heroin who wants to undergo detoxification?
Print Email page Feedback Login
Buprenorphine detoxification may be carried out at different rates

according to the person's preference, drug use, and history, although
expert opinion is that detoxification should happen very fast over a 10day period (see Table 1) or more slowly (2 mg to 4 mg per week). The
dose of buprenorphine determines the speed of reduction:
o
With higher doses, reduction can be fast.
o
With middle-range doses, the reduction is slower.
o
With lower doses, reduction may be faster, particularly when
aided by lofexidine.
Table 1. Proposed schedule for very fast detoxification from heroin using
buprenorphine.
Day of detoxification
1 2 3 4 5 6 7 8 9 10 11
Buprenorphine dose (mg) in
4 6 8
low/moderate-dose users (1 g heroin
10 8
6 4 2 0.8 0.4 stop
or less)
Buprenorphine dose (mg) in highdose users (more than 1 g heroin)
4 8 12 16 12 8 4 2 0.8 0.4 stop
Data from: [Law, Personal Communication, 2006]
Expert opinion differs on whether or not diazepam should be given.
It should only be given as part of an agreed detoxification schedule in
people who are not known to abuse it. Benzodiazepines do not reduce
the severity of withdrawal symptoms, but help the person feel better.
Diazepam may be appropriate in someone with acute withdrawal who is

requesting detoxification with buprenorphine rather than maintenance
treatment. When diazepam is prescribed as part of the management of
illicit drug use, it should be issued on the FP10MDA-SS (blue)
prescription form for daily pick-up from the pharmacy:
o
The person must be in withdrawal before buprenorphine can
be commenced, and will often be agitated.
o
Diazepam (10 mg to 20 mg) can be taken the night before
detoxification with buprenorphine is started.
o
A second dose (10 mg to 20 mg) may be taken the following
night, but it is very rare that any further doses will
be needed.
o
***********************************************************
*******************************
How should I prescribe methadone for detoxification from street
heroin?
Print
Email page
Feedback
Login

Methadone is not a good drug to use for detoxification from street
heroin.

Some clinicians and their patients may choose to use methadone.
This requires titration of the dose until symptoms and signs of
withdrawal have disappeared (see Starting maintenance treatment with
methadone) and then a reduction at a speed dependent on the individual
person but usually reducing the dose by 5 mg weekly. It is also possible
to reduce to a dose of methadone 30 mg/day or less and then switching
to buprenorphine for the final reduction. See Starting maintenance
treatment with buprenorphine.
Basis for recommendation

Methadone is the standard treatment for people who are taking
maintenance treatment but is less preferred for detoxification [RCGP,
2005b; Ford, Personal Communication, 2006].

Methadone is more commonly used for maintenance rather that
detoxification. Our reviewers stressed that buprenorphine is the first
choice drug for detoxification. Withdrawing from methadone is a
reduction leading to abstinence rather than a detoxification. The
suggested regime is based on feedback from expert reviewers.
***********************************************************
*********************************
Buprenorphine and carbamazepine as a treatment for detoxification of opiate
addicts with multiple drug misuse: a pilot study
U. Schneider 2 , W. Paetzold 2 , V. Eronat 2 , T. J. Huber 2 , J. Seifert 2 , B. Wiese 1 H.
M. Emrich 2
2 Department of Clinical Psychiatry and Psychotherapy, School of Medicine,
Hannover, Germany 1 Department of Biometry, School of Medicine, Hannover,
Germany
Correspondence to: PD Dr U. Schneider, Department of Clinical Psychiatry and
Psychotherapy, School of Medicine, 30625 Hannover, Germany Tel: 0511 5326559;
Fax: 0511 5322415; e-mail: [email protected]
Abstract
The growing tendency of opioid addicts to misuse multiple other drugs leads to the
investigation of new pharmacostrategies to prevent patients from suffering lifethreatening complications and minimize the withdrawal symptoms. The short-term
efficacy of a 10-day low-dose buprenorphine/19-day carbamazepine regime (n = 15)
to a 14-day oxazepam/19-day carbamazepine regime (n = 12) in an open-labelled
21-day inpatient detoxification treatment was compared. Twenty-seven men and
women dependent on opioids and misusing other drugs admitted to a detoxification
unit were included in this protocol. Eighteen of 27 patients (67%) completed the
study. Four non-completers (27%) received buprenorphine/carbamazepine (four of
15) and five non-completers (42%) were treated with oxazepam/carbamzepine (five
of 12), but the difference in the dropout rate between the two treatment strategies
was not significant.The buprenorphine/carbamazepine regime provided significantly
more effective relief of withdrawal symptoms during the first week of treatment. No
severe side effects occurred during treatment in both groups. The present study
supports the hypothesis that buprenorphine/carbamazepine is more effective than
oxazepam/carbamazepine in rapid opioid detoxification in patients with additional
multiple drug misuse and both regimens were safe with no unexpected side effects.
*************************************************************************************************
****************************************************
2
AU - Kutz I
AU - Reznik V
AD - Psychiatric Services, Meir General Hospital, Kfar-Saba, Israel.
[email protected]
TI - Rapid heroin detoxification using a single high dose of buprenorphine
AB - To test the effect of 32 mg of buprenorphine on the withdrawal process from
heroin, 10 street-heroin using subjects were given 32 mg of sublingual
buprenorphine, following heroin abstinence of 24 hours. Withdrawal symptoms
were monitored during the first few hours, and followed for six days after
buprenorphine administration, after which naltrexone (50 mg) was introduced to
prevent future heroin use. Nine subjects completed detoxification with negligible
withdrawal symptoms and a smooth transition to naltrexone. One subject was
excluded from the study due to methadone ingestion prior to experiment. These
results strongly suggest that painless detoxification from heroin can be obtained by
a single high dose of buprenorphine
UR - PM:11476266
SO - J Psychoactive Drugs 2001 Apr ;33(2):191-193
11
AU - Gowing L
AU - Ali R
AU - White J
AD - Evidence-Based Practice Unit, Drug and Alcohol Services Council, 161
Greenhill Road, Parkside, SA, Australia, 5067. [email protected]
TI - Buprenorphine for the management of opioid withdrawal
AB - BACKGROUND: Managed withdrawal, or detoxification, is not in itself a
treatment for opioid dependence, but it is a required first step for many forms of
longer-term treatment. It may also represent the end point of an extensive period of
treatment such as methadone maintenance. As such, managed withdrawal is an
essential component of an effective treatment system. This review is one of a series
that aims to assess the evidence as to the effectiveness of the variety of approaches
to managing opioid withdrawal. OBJECTIVES: To assess the effectiveness of
interventions involving the short-term use of buprenorphine to manage the acute
phase of opioid withdrawal. SEARCH STRATEGY: Multiple electronic databases,
including Medline, Embase, Psychlit, Australian Medical Index and Current
Contents, were searched using a strategy designed to retrieve references broadly
addressing the management of opioid withdrawal. Reference lists of retrieved
studies, reviews and conference abstracts were handsearched. SELECTION
CRITERIA: We included randomised or quasi-randomised controlled clinical trials
or prospective controlled cohort studies comparing buprenorphine (treatment 10
days or less) with another form of treatment. Studies were required to provide
detailed information on the type and dose of drugs used and the characteristics of
patients treated. Studies were also required to provide information on the nature of
withdrawal signs and symptoms experienced, the occurrence of adverse effects OR
rates of completion of the withdrawal episode. DATA COLLECTION AND
ANALYSIS: Potentially relevant studies were assessed for inclusion by one
reviewer (LG). Inclusion decisions were confirmed by consultation between
reviewers. Included studies were assessed by all reviewers. One reviewer (LG)
undertook data extraction with the process confirmed by consultation between all
three reviewers. MAIN RESULTS: Five studies met the criteria for inclusion in the
review. No data tables are included in this review and no meta-analysis has been
undertaken because of differences in treatment regimes and the assessment of
outcomes in these studies. Four studies compared buprenorphine with clonidine.
All found withdrawal to be less severe in the buprenorphine treatment group. In
three of these studies all participants were withdrawing from heroin. Participants in
one study were withdrawing from methadone, with doses reduced to 10mg/day
prior to treatment with buprenorphine. Three of the studies commented on residual
symptoms experienced by participants treated with buprenorphine to manage
heroin withdrawal. Aches, restlessness, yawning, mydriasis, tremor, insomnia,
nausea and mild anxiety were reported as being experienced by some participants.
Rates of completion of withdrawal were able to be calculated for all studies
included in the review but the definition of completion varied between studies.
Rates ranged from 65% to 100%. None of the studies included in the review
reported adverse effects. However, approximately approximately Lintzeris 1999a
approximately approximately (a single-group study which therefore did not meet
the inclusion criteria) reported 50% of participants withdrawing from heroin
experienced headaches, 28% sedation, 21% nausea, 21% constipation, 21%
anxiety, 17% dizziness and 17% itchiness during withdrawal. These adverse effects
were most common in the first 2-3 days of treatment and then subsided. In four of
the five studies treatment was undertaken on an inpatient basis. Only approximately
approximately O'Connor 1997 approximately approximately provided outpatient
treatment. However, two studies that did not meet the inclusion criteria (
approximately approximately Diamant 1998 approximately approximately and
approximately approximately Lintzeris 1999a approximately approximately ) also
provided outpatient treatment. The findings of these studies support the feasibility
of heroin withdrawal being managed with buprenorphine on an outpatient basis
UR - PM:10908521
SO - Cochrane Database Syst Rev 2000 ;(3):CD002025
*******************************************************************
************************************
12
AU - Blennow G
AU - Fergusson A
AU - Medvedeo A
AD - Universitetssjukhuset MAS, Malmo. [email protected]
TI - [Buprenorphine as a new alternative for detoxification of heroin addicts. It
causes only mild withdrawal problems, abating quickly]
AB - Buprenorphine might be an alternative drug to be used in opiate
detoxification. Its main advantage is that it carries a low risk for respiratory
depression, it gives less euphoria and limited withdrawal effects. In a pilot
detoxification project ten heroin addicts were given buprenorphine; seven
completed the course. Before detoxification seven patients showed five or more
signs on the Himmelsbach scale [6]. After the second day four patients showed no
signs, four patients displayed one sign, two patients two signs. Buprenorphine may
be a valuable alternative to clonidine, dextropropoxiphene and methadone in the
detoxification of opiate addicts
UR - PM:10815411
SO - Lakartidningen 2000 Apr 12 ;97(15):1830-1833
[Top of Page]
14
AU - Umbricht A
AU - Montoya ID
AU - Hoover DR
AU - Demuth KL
AU - Chiang CT
AU - Preston KL
AD - NIDA Intramural Research Program, Addiction Research Center, Baltimore,
MD, USA. [email protected]
TI - Naltrexone shortened opioid detoxification with buprenorphine
AB - This double-blind, randomized, placebo-controlled clinical trial evaluated the
impact on withdrawal symptoms of (i) combining naltrexone with a 4-day
buprenorphine taper for short opioid detoxification (NB Group), compared to (ii)
using a 4-day buprenorphine taper alone, followed by naltrexone on day 8 (PB
Group). Sublingual buprenorphine was administered on days 1-4 (26 mg total). For
the NB Group (n = 32) escalating doses of oral naltrexone were given on days 2-8
(placebo day 1). For the PB Group (n = 28) placebo was given on days 1-7 and
naltrexone on day 8. Main outcome measures were Observed Opioid Withdrawal
scores (OOW, 0-30) and use of medications to treat opioid withdrawal. Of 32
patients in the NB group, 59% experienced clinically relevant withdrawal (defined
as OOW > or = 5) on day 2, but, after day 5, none experienced withdrawal. In the
PB group, the number of patients experiencing withdrawal increased over time. The
first naltrexone dose induced comparable withdrawal in both groups: peak OOW
scores were (mean +/- SD) 5.2 +/- 3.3 on day 2 for the NB group, and 4.0 +/- 3.9 on
day 8 for the PB group (NS), though, on day 2, 7 patients dropped out in the NB
group and none in the PB group, while only one patient dropped out in the PB
group on day 8. Throughout the 8-day study, patients in both groups received
similar amount of adjunct medication: 0.64 +/- 0.07 mg (NB group) of clonidine vs
0.73 +/- 0.15 mg (PB group; NS). Only 25% of patients required use of sedatives
(up to 20 mg diazepam). Starting naltrexone on day 2 appeared to abolish
withdrawal symptoms after day 5 and, thus, to shorten the duration of withdrawal
symptoms. Peak withdrawal symptoms after naltrexone were of moderate intensity,
suggesting that naltrexone combined with buprenorphine is an acceptable and safe
treatment for shortened opioid detoxification and induction of naltrexone
maintenance
UR - PM:10529020
SO - Drug Alcohol Depend 1999 Oct 1 ;56(3):181-190
15
AU - Liu ZM
AU - Cai ZJ
AU - Wang XP
AU - Ge Y
AU - Li CM
AD - National Institute on Drug Dependence, Beijing Medical University, China
TI - Rapid detoxification of heroin dependence by buprenorphine
AB - AIM: To evaluate the clinical efficacy of buprenorphine (Bup) in treatment of
acute heroin withdrawal. METHODS: Bup was given sublingually daily to 60 cases
of heroin addicts in 3 groups: low, medium, and high doses. Withdrawal signs and
symptoms of heroin were rated by Clinical Institute Narcotic Assessment. Craving
for heroin during detoxification was assessed by Visual Analogue Scale. The side
effects of Bup was assessed by Treatment Emergent Symptom Scale. RESULTS:
The mean daily consumption of Bup in low, medium, and high group was 2.0, 2.9,
and 3.6 mg, respectively. Bup not only suppressed objective signs and withdrawal
symptoms for heroin withdrawal, but also reduced the duration for heroin
detoxification over 7-8 d. CONCLUSION: Bup is an effective and rapid
detoxification agent with fewer side effects for treatment of acute heroin
withdrawal
UR - PM:10072959
SO - Zhongguo Yao Li Xue Bao 1997 Mar ;18(2):112-114
AU - Vignau J
AD - Centre Hospitalier et Universitaire, Lille, France. [email protected]
TI - Preliminary assessment of a 10-day rapid detoxification programme using high
dosage buprenorphine
AB - The original French therapeutic strategy for the treatment of opioid addiction
was a rapid detoxification occasionally accompanied by treatment for withdrawal
symptoms. In 1995, substitution therapy using opioids was introduced with the aim
of maintenance, utilising methadone and the partial agonist buprenorphine,
introduced in 1996. As well as being a maintenance agent, buprenorphine has been
prescribed for rapid detoxification due to its reduced tendency to cause any
withdrawal effects and its ability to block the effects of other opioids. This trial was
initiated to measure the efficacy of buprenorphine in rapid detoxification and to
assess whether additional medication would be required. Participants in this open
study had requested rapid detoxification and were referred to the addiction clinic as
inpatients. Patients were assessed by the clinician and during counselling sessions,
and an initial dose was agreed upon. This dose was then gradually decreased over
ten days in a flexible dosing schedule, with concurrent toxicological urinalysis to
ensure no illicit drug use. During the trial, 25% of patients transferred to a
maintenance programme and 58% remained in the study. The large transfer of
patients to maintenance programmes may indicate that many people requesting
rapid detoxification are actually asking for a more generalised form of assistance.
No opioid-positive urines were noted after the fourth day in any patients, and the
study indicates that buprenorphine should prove to be a useful detoxification agent,
particularly in less hardened addicts. Step-down buprenorphine detoxification
minimises withdrawal symptoms and, therefore, reduces the need for concurrent
medication
UR - PM:9767204
SO - Eur Addict Res 1998 ;4 Suppl 1():29-31
Tramadol versus Buprenorphine for the Management of
Acute Heroin Withdrawal: A Retrospective Matched Cohort
Controlled Study
Authors: Melinda Threlkeld - Dr. Threlkeld is now in the Department of Emergency
Medicine, Carolina State Medical Center, Charlotte, NC.a; Theodore V. Parran Jr. abc;
Christopher A. Adelman bd; Scott F. Grey de; Jaehak Yu cf
Affiliations: a Department of Medicine, Case Western Reserve University School of
Medicine, Cleveland, Ohio
b
St. Vincent Charity Hospital and Rosary Hall, Cleveland, Ohio
Cleveland VA Medical Center, Cleveland, Ohio
d
Department of Family Medicine, Case Western Reserve University School of
Medicine, Cleveland, Ohio
e
Division of Epidemiology and Bio-statistics, Case Western Reserve University
School of Medicine, Cleveland, Ohio
f
Department of Psychiatry, University Hospitals of Cleveland, Cleveland, Ohio
DOI: 10.1080/10550490500528712
Publication Frequency: 6 issues per year
Published in:
American Journal on Addictions, Volume 15, Issue 2 May 2006 , pages 186
- 191
Subject: Addiction & Treatment;
Formats available: HTML (English) : PDF (English)
Article Requests: Order Reprints : Request Permissions
Purchase Article: €28.00 plus VAT - buy now
add to cart
[ show other buying
options ]
paymen
purchas custome online
t
price
e type
r type
access
method
c


Single
Article
Purchase
Any
3 days
credit
card
€28.00 plus
VAT
buy now
cart
add to
Issue
Purchase
Any
permanen
t
credit
card
€91.93 plus
VAT
buy now
cart
add to
Sign In
Online Sample
Abstract
Many medications have been used over the past thirty years for the treatment of opioid
withdrawal, including propoxyphene, methadone, clonidine, parenteral buprenorphine, and,
more recently, sublingual buprenorphine. Each has been found to have clinical strengths and
limitations. Tramadol is a centrally acting synthetic analgesic with opiate activity primarily
due to the binding of a metabolite to the μ receptor. Despite this μ receptor activity, tramadol
appears to have low abuse potential and is a non-scheduled analgesic. The pharmacologic
profile of tramadol makes it a candidate for opiate withdrawal treatment. A chart review was
undertaken to retrospectively compare treatment outcomes of heroin-dependent patients when
detoxified with parenteral buprenorphine (1996-1997) versus tramadol (1999-2000). Inclusion
criteria for this study were heroin as drug of choice, current opioid physical dependence (ie,
withdrawal symptoms), no current abuse of oral opioid analgesics, and no alcohol or
benzodiazepine withdrawal symptoms. Patient cases that met inclusion criteria were groupmatched between buprenorphine and tramadol on the basis of age, sex, and amount of heroin
used (bags/day). Charts were audited for patient demographics, daily heroin use at admission,
withdrawal symptoms, and discharge status. In total, 129 patient charts were reviewed, and
115 met all inclusion criteria and were group-matched (45 patients in the buprenorphine
group, seventy in the tramadol group). There were no differences in demographics between
the two groups of patients. Fifty-six percent of the buprenorphine group and 71% of the
tramadol group completed detoxification; tramadol-treated patients had significantly higher
average withdrawal symptoms when compared to the buprenorphine group and a greater
reduction in withdrawal symptoms over time. Finally, the number of side effects was small
and did not differ between the groups. The results of this study are consistent with previous
pilot reports that indicated few clinical differences between parenteral buprenorphine and oral
tramadol protocols when used in the management of acute heroin withdrawal. As a
consequence, tramadol shows some promise as an opioid withdrawal management
medication.
Received: 22.1.2005 Accepted: 1.6.2005
Journal of Research in Medical Sciences May & June 2006; Vol 11, No 3 185
Original Article
Tramadol versus methadone for the management of
acute opioid withdrawal: an add-on study
M. Salehi*, M. Amanatkar**, M. Barekatain*
ABSTRACT
BACKGROUND: Opioid
agonists such as methadone have been used widely in controlling opioid
withdrawal symptoms.
Tramadol, a partial opioid agonist, also has been prescribed to manage acute and chronic pain. We
sought to compare
the efficacy of tramadol and methadone in reducing the severity of opioid withdrawal symptoms.
METHODS: In a double blind clinical trial 70 opioid dependent patients who used daily opium equal to 15
mg methadone
randomly were assigned in two groups. In one group, methadone was started at 15 mg/day while in
the other
group 450 mg/day tramadol was prescribed. Both drugs were tapered in a week and placebo was
prescribed in the 2nd
week. The severity of withdrawal symptoms were assessed five times by short opioid withdrawal scale
(SOWS). Data
were analyzed by Repeated Measures Analysis of Variance, Mann-Whitney U, and Wilcoxon tests.
RESULTS: There were statistically significant differences between two groups in the severity of anxiety
(P = 0.015), irritability
(P = 0.044), palpitation (P = 0.018), agitation (P = 0.037), and dysphoria (P = 0.044) that all were more
common
in methadone group. Comparison of side effects revealed statistically significant differences in
sweating (P = 0.003) and
drowsiness (P = 0.019) between two groups that were more frequent in methadone group.
DISCUSSION: Tramadol was more efficacious in controlling opioid withdrawal symptoms with lower side
effects.
KEYWORDS: Methadone, tramadol, opioid withdrawal
Bringing Buprenorphine-Naloxone Detoxification to
Community Treatment Providers: The NIDA Clinical Trials
Network Field Experience
Leslie Amass, Ph.D., Walter Ling, M.D., Thomas E. Freese, Ph.D., Chris Reiber, Ph.D.,
M.P.H., Jeffrey J. Annon, M.A., Allan J. Cohen, M.A., M.F.T., Dennis McCarty, Ph.D.,
Malcolm S. Reid, Ph.D., Lawrence S. Brown, Jr., M.D., Cynthia Clark, M.S.N., C.R.N.P.,
Douglas M. Ziedonis, M.D., Jonathan Krejci, Ph.D., Susan Stine, M.D., Ph.D., Theresa
Winhusen, Ph.D., Greg Brigham, Ph.D., Dean Babcock, M.S.W., L.C.S.W., Joan A. Muir,
Ph.D., Betty J. Buchan, Ph.D., and Terry Horton, M.D.
In October 2002, the U.S. Food and Drug Administration approved buprenorphine-naloxone
(Suboxone®) sublingual tablets as an opioid dependence treatment available for use outside
traditionally licensed opioid treatment programs. The NIDA Center for Clinical Trials
Network (CTN) sponsored two clinical trials assessing buprenorphine-naloxone for short-term
opioid detoxification. These trials provided an unprecedented field test of its use in twelve
diverse community-based treatment programs. Opioid-dependent men and women were
randomized to a thirteen-day buprenorphine-naloxone taper regimen for short-term opioid
detoxification. The 234 buprenorphine-naloxone patients averaged 37 years old and used
mostly intravenous heroin. Direct and rapid induction onto buprenorphine-naloxone was safe
and well tolerated. Most patients (83%) received 8 mg buprenorphine-2 mg naloxone on the
first day and 90% successfully completed induction and reached a target dose of 16mg
buprenorphine-4 mg naloxone in three days. Medication compliance and treatment
engagement was high. An average of 81% of available doses was ingested, and 68% of
patients completed the detoxification. Most (80.3%) patients received some ancillary
medications with an average of 2.3 withdrawal symptoms treated. The safety profile of
buprenorphine-naloxone was excellent. Of eighteen serious adverse events reported, only one
was possibly related to buprenorphine-naloxone. All providers successfully integrated
buprenorphine-naloxone into their existing treatment milieus. Overall, data from the CTN
field experience suggest that buprenorphine-naloxone is practical and safe for use in diverse
community treatment settings, including those with minimal experience providing opioidbased pharmacotherapy and/or medical detoxification for opioid dependence.
Voir à l’adresse suivante http://pb.rcpsych.org/cgi/reprint/31/3/91
Buprenorphine Rescue from Naltrexone-Induced Opioid Withdrawal During Relatively
Rapid Detoxification from High-Dose Methadone: A Novel Approach
April 2008
by Vanessa Urban, MD; and Rolly Sullivan, MD
Dr. Urban is Clinical Instructor and Dr. Sullivan is Professor, Department of Behavioral
Health and Psychiatry, West Virginia University of Medicine, Morgantown, Virginia.
Abstract
This small series of case reports illustrates a significantly faster and well tolerated method for
a relatively rapid detoxification from high-dose methadone as compared to traditional
methadone detoxification regimens. After inducing a withdrawal state using oral naltrexone,
the patients were quickly “rescued” with buprenorphine (a combination of
buprenorphine/naloxone). By administering a medication that attenuates withdrawal
symptoms, patients immediately began to feel better and were better able to invest themselves
in the overall treatment. The patients were then able to taper off opioids in a matter of days
with minimal discomfort. The average length of stay was seven days, and no patients left
before completing the program.
Key Words
methadone, buprenorphine, suboxone, naltrexone, revia, rapid detoxification, high dose
Introduction
Opioid dependence is a growing concern in the United States. The 2003 National Survey on
Drug Use and Health showed 3.2 percent of Americans misused prescription drugs.
Abstinence remains the goal of treatment, but often patients relapse when going through the
physical withdrawal symptoms that present with opioid cessation. In today’s managed
healthcare climate, there is an ever-increasing pressure to treat patients quickly, and this is
especially true for inpatient treatments. Often patients request a faster method of
detoxification than the standard methadone taper as set forth by methadone clinics.[1 ]We
propose a novel approach to address the issue of providing a relatively rapid method of
inpatient detoxification from high dose methadone (>70mg in our review) by using a
combination of oral naltrexone followed by sublingual buprenorphine/naltrexone.
Methods
The author performed a 12-month retrospective chart review of all inpatients of the addiction
unit at a university hospital in Morgantown, West Virginia. Five patients (3 men, 2 women)
each requesting detoxification from methadone were admitted on doses of methadone ranging
from 70mg to 130mg per day. All endorsed receiving their regular methadone dose the day
prior to admission. Patients chosen for this retrospective chart review received naltrexone
followed by buprenorphine/naltrexone during their detoxification. Information was obtained
from medical records.
Background. Buprenorphine acts as a Mu partial agonist and a moderate kappa antagonist.[1–
3] The properties that make it ideal as a detoxification medication are its high affinity for and
slow dissociation from the Mu opioid receptors, its minimal withdrawal when stopped
abruptly, its minimal euphoric effects, its safety in overdose, and its ability to block receptors
from illicit opioid ingestion.[1,4,5] There is preliminary data that it may also reduce opioid
cravings.[1,4] Because buprenorphine has a higher affinity for the opioid receptor than
methadone, but only 40 percent of methadone’s efficacy, a direct methadone to
buprenorphine/naloxone regimen has proven clinically difficult unless the daily methadone
dose is 30mg or less.[1,6]
Participants. After a chart review spanning a 12-month period, five patients met the inclusion
criteria of a maintenance methadone dosage of 70mg or more per day. Patients included in
this case review were adults 18 years of age or older who had a full history and physical as
well as standard laboratory work done at the time of their admission. The daily methadone
doses of the five cases in this review were 70mg, 75mg, 100mg, 100mg, and 130mg.
Procedure. On admission, all patients were given the choice of clonidine 0.2mg tablets on an
as needed basis or weekly TTS-2 (0.2mg/24 hours) clonidine patches. The patients were then
educated regarding the induction of opioid withdrawal with naltrexone as well as the
pharmacologic properties of sublingual buprenorphine/naloxone that render it ineffective if
not taken sublingually. It was explained that after the initial oral dose of naltrexone 25mg,
opioid withdrawal symptoms typically took 30 to 45 minutes to be strong enough to warrant a
buprenorphine/naloxone dose. After this orientation to the procedure, the patients were then
given their initial naltrexone doses, encouraged to self-report any symptoms of opioids
withdrawal, and were monitored by the staff for signs and symptoms of withdrawal.
Assessments. Full opioid withdrawal was assessed by staff’s observation of vital signs, onset
of nausea, vomiting, diarrhea, rhinorrhea, and yawning in conjunction with patient’s selfreporting of muscle aches, abdominal cramping, irritability, and anxiety. An initial dose of 4
to 6mg of sublingual buprenorphine/naloxone was then given. The dosage for maintenance of
symptom relief was then obtained during the first 24-hour period of buprenorphine/naloxone
treatment. This dose was then tapered off over several days based on the individual’s clinical
course.
Results
The induction/rescue technique had promising results. Typical opioid withdrawal symptoms
occurred within 45 minutes of the naltrexone dose, and using it to induce withdrawal
circumvented a premature methadone to buprenorphine/naloxone transfer. All patients placed
on the intermediate step of naltrexone induction followed by buprenorphine/naloxone rescue
completed the detoxification process and expressed gratitude at the efficiency of the process.
Discussion
Traditionally, detoxification from high-dose methadone is a long process. The lowest daily
dose of methadone we treated was 70mg daily, which would have taken 15 weeks using a
traditional outpatient taper. Our average detoxification was seven days with naltrexoneinduced withdrawal followed by a sublingual buprenorphine/naloxone rescue.
We opted to use the “rescue” approach rather than a direct methadone to buprenorphine
approach for several reasons. The first was that withdrawal could be quickly and predictably
initiated, thus starting buprenorphine treatment sooner. Another was the concern that if a
direct methadone to buprenorphine transfer is initiated, significant withdrawal would result
due to buprenorphine being a partial agonist but at the same time having the highest affinity
for the Mu receptors. Therefore, the withdrawal would not be able to be reversed by the
addition of other opioids, which could potentially cause a higher treatment dropout rate. The
final reason was that it was felt in a dependent population, a medicine that could quickly
reverse withdrawal symptoms would increase patient confidence in the medication and thus
increase overall adherence with treatment. Although patients had to enter naltrexone-induced
withdrawal before receiving buprenorphine/naloxone, they then had a sufficient “rescue”
experience, which allowed them to complete the program. The total number of patients
reviewed was small, but there were no dropouts with this method. At the time of the review,
the issue of natural versus induced withdrawal was not addressed in the literature. It would be
helpful if double-blind, placebo-controlled studies were done to compare outcomes between
the methods of predicating withdrawal versus waiting for the natural course of withdrawal to
ensue before initiating buprenorphine treatment.
Conclusion
Although this is a small series of cases, it raises some interesting possibilities. Methadone
maintenance dosages usually range from 80mg to 120mg, and current literature endorses a
slow 3 to 5mg per week taper of this drug.6 Patients’ attempts to wean themselves faster than
this may foster relapse as signs and symptoms of withdrawal emerge, thus discouraging them
from future attempts. Buprenorphine offers relief from withdrawal and acts as a deterrent to
future illicit opioid usage secondary to its high opioid receptor affinity. It may prove
beneficial to study the methods outlined in this paper of a naltrexone-induced withdrawal
followed by a buprenorphine/naloxone rescue in controlled clinical trials.
References
1. Graham W, Schultz TK, Mayo-Smith MF, et al (eds). Principles of Addiction
Medicine, Third Edition. Maryland, Md: American Society of Addiction
Medicine, Inc., 2003.
2. Rothman RB, Ni Q, Xu H. Buprenorphine: A review of the binding
literature. In: Cowan A, Lewi JW (eds). Buprenorphine: Combating Drug
Abuse with a Unique Opioid. New York, NY: Wiley-Liss, 1995:19–30.
3. Johnson RE, Strain EC, Amass L. Buprenorphine: How to use it right. Drug
Alcohol Depend 2003;70:S59–S77.
4. Fudala, PJ, et al. Office-based treatment of opiate addiction with a
sublingual-tablet formulation of buprenorphine and naloxone. N Engl J Med
2003;349(10):949–58.
5. Johnson, RE. Buprenorphine and naloxone for heroin dependence. Curr
Psychiatry Rep 2000;2(6):519–26.
6. McNicholas L. Clinical Guidelines for the Use of Buprenorphine in the
Treatment of Opioid Addiction: A Treatment Improvement Protocol TIP 40.
Department of Health and Human Services, 2004. Available at:
http://www.samhsa.gov/SAMHSA_News/VolumeXII_4/article7.htm. Access
date: April 7, 2008.
Titre du document / Document title
Low-dose buprenorphine detoxification in long term methadone addicts
Auteur(s) / Author(s)
JANIRI L. ; MANNELLI P. ; SERRETTI A. ; TEMPESTA E. ;
Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)
Catholic univ., dep. psychiatry, drug addiction unit, Rome, ITALIE
Résumé / Abstract
Discontinuation from long-term methadone is considered a problematic issue.
Various pharmacological protocols for detoxification have been proven.
Buprenorphine has recently been proposed as a promising drug in treating opioid
withdrawal syndrome. The aim of this study was to describe the time course of
withdrawal symptomatology of long-term methadone addicts treated with low doses
of buprenorphine. Long-term methadone dependent inpatients were included in a 9day open detoxification trial. Characterization of subjective, objective and
psychological opioid withdrawal symptoms was performed through an evaluation of
the time course (days 0-8) of single items of a 27 items rating scale. Buprenorphine
resulted to be an active and well tolerated drug
Revue / Journal Title
Regulatory peptides ISSN 0167-0115 CODEN REPPDY
Source / Source
Congrès
INRC : international narcotics research conference No24, Skövde , SUEDE
(10/07/1993)
1994, SUP1 (4 ref.), pp. S289-S290
Langue / Language
Anglais
Editeur / Publisher
Elsevier, Amsterdam, PAYS-BAS (1980) (Revue)
Mots-clés anglais / English Keywords
Drug addiction ; Withdrawal syndrome ; Deintoxication ; Treatment ; Chemotherapy ;
Human ; Opiates ;
Mots-clés français / French Keywords
Toxicomanie ; Sevrage syndrome ; Désintoxication ; Buprénorphine ; Traitement ;
Chimiothérapie ; Homme ; Opiacés ;
Mots-clés espagnols / Spanish Keywords
Toxicomanía ; Destete síndrome ; Desintoxicación ; Tratamiento ; Quimioterapia ;
Hombre ; Opiados ;
Localisation / Location
INIST-CNRS, Cote INIST : 18854, 35400004933769.1410
Buprenorphine versus dihydrocodeine
for opiate detoxification in primary care:
a randomised controlled trial
Nat MJ Wright1 , Laura Sheard1 , Charlotte NE Tompkins1 , Clive E
Adams2 , Victoria L Allgar1 and Nicola S Oldham3
1
Centre for Research in Primary Care, 71-75 Clarendon Road, Leeds, LS2 9PL,
UK
2
Department of Psychiatry, 15 Hyde Terrace, Leeds, LS2 9L, UK
3
Formerly of NFA Health Centre for Homeless People, 68 York Street, Leeds,
LS9 8AA, UK
author email corresponding author email
BMC Family Practice 2007, 8:3doi:10.1186/1471-2296-8-3
The electronic version of this article is the complete one and can be found online
at: http://www.biomedcentral.com/1471-2296/8/3
Received:
16 May 2006
Accepted:
8 January 2007
Published: 8 January 2007
© 2007 Wright et al; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/2.0),
which permits unrestricted use, distribution, and reproduction in any medium,
provided the original work is properly cited.
Abstract
Background
Many drug users present to primary care requesting detoxification from
illicit opiates. There are a number of detoxification agents but no
recommended drug of choice. The purpose of this study is to compare
buprenorphine with dihydrocodeine for detoxification from illicit opiates in
primary care.
Methods
Open label randomised controlled trial in NHS Primary Care (General
Practices), Leeds, UK. Sixty consenting adults using illicit opiates received
either daily sublingual buprenorphine or daily oral dihydrocodeine.
Reducing regimens for both interventions were at the discretion of
prescribing doctor within a standard regimen of not more than 15 days.
Primary outcome was abstinence from illicit opiates at final prescription as
indicated by a urine sample. Secondary outcomes during detoxification
period and at three and six months post detoxification were recorded.
Results
Only 23% completed the prescribed course of detoxification medication
and gave a urine sample on collection of their final prescription. Risk of
non-completion of detoxification was reduced if allocated buprenorphine
(68% vs 88%, RR 0.58 CI 0.35–0.96, p = 0.065). A higher proportion of
people allocated to buprenorphine provided a clean urine sample
compared with those who received dihydrocodeine (21% vs 3%, RR 2.06
CI 1.33–3.21, p = 0.028). People allocated to buprenorphine had fewer
visits to professional carers during detoxification and more were abstinent
at three months (10 vs 4, RR 1.55 CI 0.96–2.52) and six months post
detoxification (7 vs 3, RR 1.45 CI 0.84–2.49).
Conclusion
Informative randomised trials evaluating routine care within the primary
care setting are possible amongst drug using populations. This small study
generates unique data on commonly used treatment regimens.
Background
In the United Kingdom (UK), policy directives have highlighted the
importance of offering either maintenance or detoxification to illicit opiate
users within an agreed plan of care [1]. This is in response to routine
practice by some treatment providers of 'gradual reduction' of opiate
maintenance treatment – a regimen without a supporting evidence base
[2]. Opiate detoxification, using one of various therapeutic agents,
remains an important part of drug management for some illicit opiate
users. However, neither the evidence base nor UK national guidelines
recommend a 'drug of choice' [1]. Understandably, there has been a call
for randomised controlled trials (RCTs) in this area [3]. In primary care,
methadone is commonly used, with reductions in the dose over 7–21 days
[4]. Methadone has a long half life [5,6] and patients often report
distressing withdrawal symptoms in the latter stages of detoxification [6].
This has meant increasing use of alternative agents such as clonidine,
lofexidine, dihydrocodeine and, more recently, buprenorphine. The
hypotensive effects of clonidine [4] have make it unacceptable for use in
primary care and the reduced ability of lofexidine to control withdrawal,
coupled with its high cost have resulted in limited clinical uptake [4].
The use of sublingual buprenorphine is relatively new in the UK for opiate
detoxification and there have been only two randomised controlled trials
(RCTs) comparing it with methadone for this purpose [7,8].
Buprenorphine has been more commonly used as a drug of comparison in
trials of opiate maintenance [9-16]. A recent Cochrane review assessing
methadone and buprenorphine for the management of opioid withdrawal
found no significant difference between these two agents [17]. In this
context, buprenorphine has a good safety profile, better retention in
treatment and lower withdrawal severity [18-22]. Sublingual
buprenorphine is increasingly being prescribed by General Practitioners
(GPs) for opiate detoxification [23] despite limited clinical and research
evidence.
Dihydrocodeine has a shorter half life than methadone and has been
widely used in both primary care and prison drug treatment settings for
opiate detoxification. Whilst some commentators have documented
success with dihydrocodeine [24,25] others have expressed concerns
regarding its effects, particularly the potential diversion into the street
economy [26]. Despite routine use, dihydrocodeine has rarely been
studied for the purposes of opiate detoxification [24] but has been
compared in a randomised controlled trial with buprenorphine for
postoperative pain [27].
When comparing methadone, dihydrocodeine and buprenorphine it is
important to note several factors which may impact upon prescribing and
use of these agents. Dihydrocodeine is cheaper than methadone and both
methadone and dihydrocodeine are substantially cheaper than
buprenorphine. The latter has been subject to heavy pharmaceutical
marketing. Buprenorphine and dihydrocodeine have a better safety profile
than methadone, which has a high toxicity which (rarely) can result in
death [28]. All three agents have the potential for street diversion but
dihydrocodeine is the hardest to control, with consumption usually being
unsupervised. Methadone is the easiest to manage and buprenorphine
seems to be somewhere in-between.
The care of people using illicit opiates has changed over recent years.
Strang et al (2005) [29] surveyed GPs and found that half had seen at
least one opiate user in a four week period, compared to only 19% in a
1986 survey [30]. There has been a significant increase in the number of
GPs becoming involved in the care of drug users [31]. Consequently,
many short term opiate detoxifications are now undertaken in primary
care. The absence of robust evidence underpinning many of the clinical
decisions made within primary care has already been highlighted [32].
LEEDS (Leeds Evaluation of Efficacy of Detoxification Study) is a response
to this challenge and compared dihydrocodeine with buprenorphine for
opiate detoxification within the UK primary care setting.
Methods
Design and setting
LEEDS was conducted in ten general practices (6 of which randomised
participants) in Leeds, UK (population ~750,000). We used a randomised
controlled trial design to compare open giving of oral dihydrocodeine
tartrate with open giving of sublingual buprenorphine. Randomisation was
by random block size, stratified by practice, using Microsoft Excel RAND
function. This was undertaken by the Department of Psychiatry, University
of Leeds, and was concealed from clinicians prescribing interventions. The
name of the allocated intervention was obscured within fully opaque
sealed envelopes [33]. All envelopes were opened in strict order,
confirmed by an investigator independent of the clinical interface. The
outside of the randomisation envelope contained a brief information form
to be completed which requested the patient's practice number, date of
birth, contact telephone number and date of first prescription. Two
questions also served to rate the severity of addiction of the participant
from the view of the GP. Once the GP/drug worker opened the LEEDS
envelope both practitioner and patient knew the intervention, standard
clinical care resumed and the patient made subsequent appointments with
the GP and/or drugs worker. To detect with 80% power a difference in
treatment effectiveness of 25% between groups (50% versus 25%) at 5%
level of significance, it was calculated that 120 participants would be
needed in the study. However within the time frame for recruitment we
were only able to recruit 60 participants. Randomisation took place
between August 2002 and May 2004. Full methods are reported elsewhere
[33].
The Leeds Teaching Hospitals Local NHS Research Ethics Committee
(LREC) approved the study in April 2002. Informed written consent was
obtained from each patient following receipt of a participant information
leaflet prior to their involvement in the trial.
Interventions
Buprenorphine was prescribed on an FP10 MDA prescription. This allows
daily dispensing under supervision of a pharmacist. Daily supervised
administration of dihydrocodeine tablets is not possible in the UK as it
cannot be prescribed on FP10 MDA prescriptions. As such, buprenorphine
was dispensed either as 8 mg, 2 mg or 0.4 mg sublingual tablet
preparation under daily supervision. Dihydrocodeine was dispensed as 30
mg rapid release tablet preparation in take home installments. Each
installment was for a minimum of three and a maximum of 4 daily doses.
The reducing regimens for both interventions were at the discretion of the
prescribing doctor and within the standard regimen which was
approximately 15 days (Tables 1 and 2). However, clinicians were free to
titrate doses against withdrawal symptoms. What was being randomised
was the open giving of the drugs even if that meant that participants were
not given in the opinion of the prescribing doctor pharmacologically
equivalent dosages.
Table 1. Standard buprenorphine detoxification
Table 2. Standard dihydrocodeine detoxification
Inclusion and exclusion criteria
Patients were eligible for the study if they were: aged 18 years or over,
using street opiates as confirmed by a urine sample taken at first
assessment, wishing to detoxify through the standard monitored process,
willing to remain abstinent from opiates and to give informed consent.
Patients were excluded if they had contra-indications to dihydrocodeine or
buprenorphine or had been randomised into the trial previously.
Outcomes
The primary outcome was abstinence from illicit heroin at final
prescription, as indicated by urine test. A priori we classed unsuccessful
detoxification as: the final urine tested positive for metabolic breakdown
products of heroin (morphine or 6-mono-acetyl morphine); urine tested
positive for opiates commonly found in street heroin (codeine); the patient
did not provide a final urine sample; did not finish detoxification or
reported using street opiates during the period of detoxification. We
recorded the secondary outcomes of inappropriate use of prescribed
medication, overdose and admission to hospital or Accident and
Emergency (A&E) and number of GP/drug worker visits during the
detoxification period. At three and six month post detoxification, follow up
data were recorded. These outcomes were: whether the person was still
alive, abstinent from opiates, in receipt of sickness certification and their
pattern of service use.
Statistical analysis
Outcome data were analysed using Epi Info v 3.3.2 and SPSS software
with relative risk tests for categorical data and unpaired t-tests for
continuous data.
Results
Sixty people using illicit opiates took part in LEEDS (Figure 1). This
comprised of 42 men and 18 women, with an average age of 28 years.
58% were homeless or unstably housed. There were no significant
differences for those allocated to one regimen or the other (Table 3).
Figure 1.
Table 3. Demographic characteristics and prognostic factors
Overall, only 13 people (23%) completed the prescribed course of
detoxification medication and gave a urine sample on collection of their
final prescription (Table 4). There was an increased chance of completing
the prescribing regime if allocated buprenorphine though this finding was
of borderline statistical significance (68% vs 88%, RR 0.58 CI 0.35–0.96,
p = 0.065). At completion of detoxification, by intention to treat analysis
we found a higher proportion of people allocated to buprenorphine
provided a urine sample negative for opiates (abstinent) compared with
those who received dihydrocodeine (21% vs 3%, RR 2.06 CI 1.33–3.21, p
= 0.028). This suggestion of an enhanced therapeutic effect with
buprenorphine was negated if we assumed that the proportions of those
returning with clean urine per group were representative of those who did
not return. Had all the medication been both prescribed and dispensed
according to the standard regimes, an expected mean prescribed dose for
each dihydrocodeine detoxification would be 4560 mg and 56 mg for each
buprenorphine dose. The actual amount of milligrams (mean) and
duration of detoxification in days (mean) prescribed for each
dihydrocodeine detoxification was 4111 mg (90% of expected dose) over
12 days and 32.9 mg (59% of expected dose) of buprenorphine over 9
days (both rounded to nearest day). This would indicate under-prescribing
by doctors for both regimes as 4290 mg (94% of expected dose) would
have expected to be prescribed over 12 days for dihydrocodeine and 47.6
mg (85% of expected dose) over 9 days for buprenorphine.
Table 4. Results
There was no statistically significant differences for any other outcomes
although throughout the trial people allocated to buprenorphine did better
than those on dihydrocodeine. For example people allocated to
buprenorphine had fewer visits to the GP and drugs worker during
detoxification, and more were abstinent at the three month (10 vs 4, RR
1.55 CI 0.96–2.52) and six month (7 vs 3, RR 1.45 CI 0.84–2.49) follow
up. These findings were of borderline statistical significance. No serious
adverse events were reported for any participants.
Discussion
Commentators have listed significant barriers to conducting randomised
controlled trials in the primary care setting [34,35]. Barriers certainly may
include lack of clinical equipoise towards interventions and patient
preference for a particular treatment, [36] as well as logistical problems
(principally the busy primary care workplace as not being conducive to
practitioner participation) and over-optimism regarding recruitment [37].
This study, however, was at the outset designed collaboratively between
primary care and secondary care researchers to be conducted specifically
in the primary care setting. It did not greatly complicate routine treatment
and recorded clear and concrete outcomes of relevance to the primary
care drug treatment field [33]. The LEEDS project team sought GPs
experience of being involved in the trial through a cross sectional survey.
Details of the practicalities of conducting LEEDS (including recruitment
issues and equipoise) have been fully described elsewhere [38].
LEEDS is the first randomised controlled trial to compare buprenorphine
and dihydrocodeine for opiate detoxification. Sixty people with problems
of opiate dependence agreed to take part in this randomised trial. Thirty
five of these people were recruited from a medical centre for the
homeless. Recruitment of practitioners was problematic though
recruitment of participants was not a substantial problem for practitioners
committed to recruiting into the trial. This study ran on a very low budget
(50% research assistant time). LEEDS illustrates how such studies,
undertaken in the context of routine care, even with such potentially
problematic clientele, are both possible and feasible.
One limitation of LEEDS was that it was underpowered to detect with
confidence clear differences for secondary outcomes between regimens.
Selecting a data collection point for the primary outcome at completion of
detoxification could be seen as a limitation of the study. However, this
outcome was selected after careful consideration. Ideally urine collection
would be several days post-detoxification to allow for all prescribed
opiates to be clear from the test. We thought, however, many users would
not attend primary care after completion of detoxification simply to
provide a urine test, particularly as much of the recruitment was from a
homeless population who have been traditionally difficult to engage and
retain in treatment services [39]. Indeed, only 23% of participants
provided a final urine sample. Reasons for this are varied and multiple
(Figure 1). Fourteen people did not collect their final prescription and
therefore were not available at this time point to provide a urine sample.
Five people never returned to the GP practice to collect any prescriptions
after their first consultation with the GP or drugs worker. Additionally, 24
people failed to collect a prescription somewhere between the second and
penultimate. The high numbers of people who did not provide a urine
sample demonstrates the difficulty in retaining injecting drug users in
treatment services. This pragmatic, low budget study only sought to
record contact with GPs and drugs workers and did not have sufficient
capacity to make personal contact during the detoxification period to
obtain abstinence status independent of that recorded through medical
contact.
The main objectives of LEEDS were to have some indication of whether
one regimen was associated with better odds of completing detoxification
and to test methods for larger studies. We recognize that these are limited
goals but found no indication from the literature or even experts in the
field that data was known for these outcomes. Of course, retention in
treatment services post-detoxification is an important part of the whole
treatment package offered to drug users so we also recorded the
frequency of medical service utlisation by participants.
An additional limitation of the study is that we were unable to collect data
on the numbers and demographics of those people who declined to
participate. This was due to the busy nature of the primary care treatment
setting.
Currently many drug users arrested for crimes related to drug misuse are
offered a choice of legally mandated treatment (referred to by some as
'coerced' treatment) [40] or a custodial sentence. No participant in LEEDS
had been legally mandated to enter treatment from the criminal justice
system. Consequently, all participants expressed self motivation to
undergo detoxification. Yet, regardless of which detoxification drug people
were randomised to, completion rates were poor. This study suggests that
even in this relatively self motivated group of people, completion rates
were between only 13% and 32%. In secondary care others have reported
completion rates in the range of 33% [41]. However comparisons with
study retention rates from trials undertaken in secondary care should be
made with caution as it is possible that participants were not equivalent in
terms of motivation and self-efficacy. More evaluation of treatment effects
in different health settings would therefore seem prudent and we have
nearly completed a larger study in the prison setting. The results of this
current study, however, are generalisable to those patients presenting for
detoxification from illicit opiates in primary care. We would be less
confident of generalising our findings to the residential or inpatient
setting.
This trial suggests that buprenorphine may be able to deliver 20% more
completion than dihydrocodeine. If completion of detoxification is
associated with remaining abstinent, use of buprenorphine as an agent of
opiate detoxification could be a very important step forward. Whilst
clinicians prescribing the interventions were not blinded beyond the point
of randomisation, the difference favouring buprenorphine could be due to
increased professional input for that intervention. However there was no
evidence to suggest that this was the case. Rather, there was no
suggestion of a difference in GP/drug worker visits between the two
groups. LEEDS was a "real-world" trial with a pragmatic rather than
explanatory design. As such it randomised interventions which are used in
everyday clinical practice. Previous commentators have spoken about the
need to balance issues of methodological rigour (commonly referred to as
internal validity) versus the feasibility of conducting trials in the real world
clinical environment (commonly referred to as external validity) [42].
Inevitably there is a trade off between rigour and feasibility. For example
in this case whilst the use of dummy pills was considered at the design
stage, it was deemed unfeasible as it would both add to the cost of the
research and also limit the independence of the trial from pharmaceutical
company funding.
It could also be argued that the superior percentage of those achieving
abstinence as a result of the buprenorphine intervention was because
mean buprenorphine and dihydrocodeine doses were not equivalent in
terms of the pharmacological opiate effect. However this is not possible to
verify as the two interventions are not identical in terms of action on
opiate receptors. Buprenorphine has the unusual property of being both a
partial MU receptor (one of a number of opiate receptors) agonist and
partial opiate antagonist whereas dihydrocodeine is a full opiate receptor
agonist.
Conclusion
Only 23% of participants completed their detoxification and gave a final
urine sample. This finding suggests a high non-completion rate of primary
care opiate detoxifications. A higher proportion of people randomised to
buprenorphine provided a final urine sample negative for illicit opiates
compared with those who received dihydrocodeine. Those allocated
buprenorphine made fewer visits to the GP and drugs worker during
detoxification. Additionally, more of those allocated buprenorphine were
abstinent at three and six months post detoxification when compared to
the dihydrocodeine group.
Currently in some treatment services in the UK the open giving of
dihydrocodeine has continued despite an absence of evidence to support
its clinical effectiveness. More recently, there has been a marked increase
in the prescribing of buprenorphine in the UK [23]. Such an increase is in
line with emerging best practice primary care guidance based primarily
upon face validity for opiate detoxification. This guidance supports the use
of buprenorphine but not dihydrocodeine for opiate detoxification in the
primary care setting [43]. The LEEDS findings begin to support this
guidance with good evidence but there is some way to go before fully
confident recommendations can be made.
The findings will also have relevance to any review of current Department
of Health best practice guidelines for the treatment of substance misuse
[4]. Launched in 1999, they argued that GP prescribing of buprenorphine
requires a greater level of clinical experience than the prescribing of
dihydrocodeine. The guidelines recommend buprenorphine should only be
given by a "specialist general practitioner" and dihydrocodeine by an
"experienced" GP [4]. LEEDS provides little evidence to support the
continued prescribing of dihydrocodeine as a first line agent for opiate
detoxification by less experienced GPs in primary care, but larger, well
designed, conducted and reported trials are necessary.
Competing interests
The author(s) declare that they have no competing interests.
Authors' contributions
NW and CA designed the study, offered project supervision and drafted
the manuscript. NW was principal investigator. CA centrally managed the
randomisation process and conducted statistical analysis. LS coordinated
and managed the project during the latter stages, collected data and
drafted the manuscript. CT conducted data collection and drafted the
manuscript. VA conducted statistical analysis and commented on the
results section. NO was the initial project coordinator, who assisted in the
design of the study and collected data. All authors have read and
approved the final manuscript.
Funding body
Leeds Primary Care Trusts Research Consortium Priorities and Needs
Funding.
Ethics committee
Leeds Teaching Hospitals Local Research Ethics Committee.
Acknowledgements
We are grateful to all patients at surgeries in Leeds who participated in
the trial. We would particularly like to thank Drs Paul Glynn, Sally Read
and Will Bolland, drug workers and reception.
Staff who form the LEEDS project collaborative. We also thank Leeds
Primary Care Trusts Research Consortium Priorities and Needs Funding
who funded the project.
References
1. National Treatment Agency: Models of Care: for Adult Drug
Misusers. Department of Health, London; 2002.
Return to text
2. Gossop M, Marsden J, Stewart D, Treacy S: "Outcomes after
methadone maintenance and methadone reduction
treatments: two year follow up results from the National
Treatment Outcome Research Study".
Drug and Alcohol Dependence 2001, 62:255-264. Publisher Full
Text
Return to text
3. MacLeod J, Whittaker A, Robertson R: "Changes in opiate
treatment during attendance at a community drug service
– findings from a clinical audit".
Drug and Alcohol Review 1998, 17:19-25. Publisher Full Text
Return to text
4. Department of Health, Scottish Office Department of
Health, Welsh Office, & Department of Health and Social
Services, N. I In Drug Misuse and Dependence – Guidelines on
Clinical Management. The Stationary Office, London; 1999.
Return to text
5. Lowinson J, Berle B, Langrod J: "Detoxification of long-term
methadone patients: problems and prospects".
International Journal of the Addictions 1976, 11(6):1009-1018.
PubMed Abstract
Return to text
6. Seivewright N: Community Treatment of Drug Misuse: More than
Methadone. Cambridge University Press, Cambridge; 2000.
Return to text
7. Bickel W, Stitzer M, Bigelow G, Liebson I, Jasinski D, Johnson R:
"A clinical trial of buprenorphine: comparison with
methadone in the detoxification of heroin addicts".
Clinical Pharmacology and Therapeutics 1988, 43:72-78.
Return to text
8. Seifert J, Metzner C, Paetzold W, Borsutzky M, Passie T, Rollnik J,
Wiese B, Emrich H, Schneider U: "Detoxification of opiate
addicts with multiple drug abuse: a comparison of
buprenorphine vs. methadone".
Pharmacopsychiatry 2002, 35:159-164. PubMed Abstract |
Publisher Full Text
Return to text
9. Fischer G, Gombas W, Eder H, Jagsch R, Peternell A, Stuhlinger
G, Pezawas L, Aschauer H, Kasper S: "Buprenorphine versus
methadone maintenance for the treatment of opioid
dependence".
Addiction 1999, 94:1337-1347. PubMed Abstract | Publisher Full
Text
Return to text
10. Johnson R, Chutuape M, Strain E, Walsh S, Stitzer M, Bigelow
E: "A comparison of levomethadyl acetate, buprenorphine
and methadone for opioid dependence".
New England Journal of Medicine 2000, 343:1290-1297. PubMed
Abstract | Publisher Full Text
Return to text
11. Kosten T, Schottenfield R, Ziedonis D, Falcioni J:
"Buprenorphine versus methadone maintenance for opioid
dependence ".
Journal of Nervous and Mental Disease 1993, 181:358-364.
Publisher Full Text
Return to text
12. Ling W, Wesson D, Charuvastra C, Klett C: "A controlled
trial comparing buprenorphine and methadone
maintenance in opioid dependence".
Archives of General Psychiatry 1996, 53:401-407. PubMed
Abstract
Return to text
13. Mattick R, Ali R, White J, O'Brien S, Wolk S, Danz C:
"Buprenorphine versus methadone maintenance therapy:
a randomised double blind trial with 405 opioid dependent
patients".
Addiction 2003, 98:441-452. PubMed Abstract | Publisher Full
Text
Return to text
14. Pani P, Maremmani I, Pirastu R, Tagliamonte A, Gessa G:
"Buprenorphine: a controlled clinical trial in the treatment
of opioid dependence".
Drug and Alcohol Dependence 2000, 60:39-50. Publisher Full
Text
Return to text
15. Petitjean S, Stohler R, Deglon J, Livoti S, Waldvogel D,
Uehlinger C, Ladewig D: "Double blind randomized trial of
buprenorphine and methadone in opiate dependence".
Drug and Alcohol Dependence 2001, 62:97-104. Publisher Full
Text
Return to text
16. White R, Alcorn R, Feinmann C: "Two methods of
community detoxification from opiates: an open label
comparison of lofexidine and buprenorphine".
Drug and Alcohol Dependence 2001, 65:77-83. Publisher Full
Text
Return to text
17. Gowing L, Ali R, White J: "Buprenorphine for the
management of opioid withdrawal".
The Cochrane Database of Systematic Reviews 2006., (2):
Return to text
18. Cheskin L, Fudala P, Johnson R: "A controlled comparison
of buprenorphine and clonidine for acute detoxification
from opioids".
Drug and Alcohol Dependence 1994, 36(2):115-121. Publisher
Full Text
Return to text
19. Lintzeris N, Bammer G, Jolley D, Rushworth L: "A
randomised controlled trial of buprenorphine in the
management of short term ambulatory heroin
withdrawal".
Addiction 2002, 11:1395-1404. Publisher Full Text
Return to text
20. Nigam A, Ray R, Tripathi B: "Buprenorphine in opiate
withdrawal: a comparison with clonidine".
Journal of Substance Abuse Treatment 1993, 10(4):391-394.
PubMed Abstract | Publisher Full Text
Return to text
21. O'Connor P, Carroll K, Shi J, Schottenfield R, Kosten T,
Rounsaville B: "Three methods of opioid detoxification in a
primary care setting: a randomized trial".
Annals of Internal Medicine 1997, 127(7):526-530. PubMed
Abstract | Publisher Full Text
Return to text
22. Simoens S, Matheson C, Bond C, Inkster K, Ludbrook A: "The
effectiveness of community maintenance with methadone
or buprenorphine for treating opiate dependence".
British Journal of General Practice 2005, 55:139-146. PubMed
Abstract | Publisher Full Text | PubMed Central Full Text
Return to text
23. de Wet C, Reed L, Bearn J: "The rise of buprenorphine
prescribing in England: analysis of NHS regional data,
2001–03".
Addiction 2005, 100:495-499. PubMed Abstract | Publisher Full
Text
Return to text
24. Banbery J, Wolff K, Raistrick D: "Dihydrocodeine. A useful
tool in the detoxification of methadone-maintained
patients".
Journal of Substance Abuse Treatment 2000, 19(3):301-305.
PubMed Abstract | Publisher Full Text
Return to text
25. Robertson R, Witcomb J, Roberts J, Egan J: " Misuse of
dihydrocodeine tartrate (DF 118) among opiate addicts
(letter)".
British Medical Journal 1990, 301:119.
Return to text
26. Swadi H, Wells B, Power R: "Misuse of dihydrocodeine
tartrate (DF 118) among opiate addicts".
British Medical Journal 1990, 300:1313. PubMed Abstract |
PubMed Central Full Text
Return to text
27. Masson A: "Sublingual buprenorphine versus oral
dihydrocodeine in post-operative pain".
Journal of International Medical Research 1981, 9(6):506-510.
PubMed Abstract
Return to text
28. Zador D, Sunjic S: "Deaths in methadone maintenance
treatment in New South Wales, Australia 1990–1995".
Addiction 2000, 95(1):77-84. PubMed Abstract | Publisher Full
Text
Return to text
29. Strang J, Sheridan J, Hunt C, Kerr B, Gerada C, Pringle M:
"The prescribing of methadone and other opioids to
addicts: national survey of GPs in England and Wales".
British Journal of General Practice 2005, 55:444-451. PubMed
Abstract | Publisher Full Text | PubMed Central Full Text
Return to text
30. Glanz A, Taylor C: "Findings of a national survey of the
role of general practitioners in the treatment of opiate
misuse: extent of contact".
British Medical Journal 1986, 293:427-430. PubMed Abstract |
PubMed Central Full Text
Return to text
31. Davies A, Huxley P: "Survey of general practitioners
opinions on treatment of opiate users".
British Medical Journal 1997, 314:1173. PubMed Abstract |
Publisher Full Text
Return to text
32. Horton R: "Evidence and primary care".
Lancet 1999, 353:609. PubMed Abstract | Publisher Full Text
Return to text
33. Oldham N, Wright N, Adams C, Sheard L, Tompkins C: "The
Leeds Evaluation of Efficacy of Detoxification Study
(LEEDS) Project: An open label pragmatic randomised
control trial comparing the efficacy of differing therapeutic
agents for primary care detoxification from either street
heroin or methadone – ISRCTN07752728".
BMC Family Practice 2004., 5(1):PubMed Abstract | Publisher Full
Text | PubMed Central Full Text
Return to text
34. Fairhurst K, Dowrick C: "Problems with recruitment in a
randomised controlled trial of counselling in general
practice: causes and implications".
Journal of Health Service Research Policy 1996, 1(2):77-80.
Return to text
35. Hetherton J, Matheson A, Robson M: "Recruitment by GPs
during consultations in a primary care randomised
controlled trial comparing computerised psychological
therapy with clinical psychology and routine GP care:
problems and possible solutions".
Primary Health Care Research and Development 2004, 5:5-10.
Publisher Full Text
Return to text
36. Ward E, King M, Lloyd M, Bower P, Friedli K: "Conducting
randomised trials in general practice: methodological and
practical issues".
British Journal of General Practice 1999, 49:919-922. PubMed
Abstract | Publisher Full Text | PubMed Central Full Text
Return to text
37. van der Windt D, Koes B, van Aarst M, Heemskerk M, Bouter
L: "Practical aspects of conducting a pragmatic
randomised trial in primary care: patient recruitment and
outcome assessment".
British Journal of General Practice 2000, 50:371-374. PubMed
Abstract | Publisher Full Text | PubMed Central Full Text
Return to text
38. Sheard L, Tompkins C, Wright N, Adams C: "Recruiting
opiate users to a randomized controlled trial in primary
care: A descriptive study of GP attitudes".
Primary Health Care Research and Development 2006, 7:106115. Publisher Full Text
Return to text
39. Wright N, Tompkins C: "How can health services
effectively meet the health needs of homeless people".
British Journal of General Practice 2006, 56:286-293. PubMed
Abstract | Publisher Full Text
Return to text
40. Ashton M: "Force in the Sunshine State.".
Drug and Alcohol Findings 2000, 4:21-25.
Return to text
41. Vanichseni S, Wongsuwan B, Choopanya K, Wongpanich K: "A
controlled trial of methadone maintenance in a population
of intravenous drug users in Bangkok: implications for
prevention of HIV".
The International Journal of the Addictions 1991, 26(12):1313-
1320. PubMed Abstract
Return to text
42. Carrol K, Farentinos C, Ball S, Crits-Christoph P, Libby B,
Morgenstern J, Obert J, Polcin D, Woody G: "MET meets the
real world: design issues and clinical strategies in the
Clinical Trials Network".
Journal of Substance Abuse Treatment 2002, 23(2):73-80.
PubMed Abstract | Publisher Full Text
Return to text
43. Royal College of General Practitioners: RCGP Guide to the
Management of Substance Misuse in Primary Care. Royal College
of General Practitioners, London; 2005.
Return to text
Pre-publication history
The pre-publication history for this paper can be accessed here:
http://www.biomedcentral.com/1471-2296/8/3/prepub
Have something to say? Post a
comment on this article!
Terms and Conditions Privacy statement Information for advertisers Jobs at BMC
Contact us
© 1999-2008 BioMed Central Ltd unless otherwise stated. Part of Springer
Science+Business Media.
Methadone detoxification of tramadol dependence . Journal of Substance Abuse
Treatment , Volume 19 , Issue 3 , Pages 297 - 299 R . Leo
bstract
Tramadol hydrochloride is a centrally acting analgesic
with a partial affinity for the opiate receptor (μ), having
an analgesic potency estimated to be one tenth that of
morphine. While preclinical investigations suggested
that abuse liability associated with tramadol use is low,
there are increasing numbers of cases reported to the
U.S. Food and Drug Administration of abuse,
dependence, and withdrawal associated with tramadol
use. A case of a patient with tramadol dependence
requiring detoxification with methadone is presented.
Acute management of significant tramadol dependence
has not yet been reported in the literature. Long-term
treatment issues are also discussed.
Differences in heroin addicts seeking inpatient detoxification,
ambulatory detoxification, or methadone maintenance.
Steer RA.
Fifteen psychosocial characteristics of 300 male and 90 female
heroin addicts admitted for inpatient detoxification, ambulatory
detoxification, and methadone maintenance within the same
multiphasic drug-abuse program were compared to determine
whether or not their characteristics differentiated those seeking
each type of treatment approach; there were 100 men and 30
women randomly drawn to represent each of the three
approaches. Only two variables differed among the three
approaches for both men and women--length of daily heroin use
and educational attainment. The ambulatory detoxification
patients had started using heroin daily at a later age than the
inpatients who, in turn, had started using heroin daily at a later
age than the methadone maintenance patients, and the
ambulatory detoxification patients were more educated than the
inpatients. The other variables differentiating the three
approaches for each sex were discussed, and the conclusion was
drawn that addicts with higher socioeconomic levels preferred
ambulatory detoxification over methadone maintenance.
PMID: 510180 [PubMed - indexed for MEDLINE]
Suspected determinants of enrollment into detoxification and
methadone maintenance treatment among injecting drug users.
Schütz CG, Rapiti E, Vlahov D, Anthony JC.
National Institute on Drug Abuse/Intramural Research Program, Etiology
Branch, Baltimore, MD 21224.
Our primary aim in this study has been to evaluate selected
conditions thought to influence the entry of injecting drug users
(IDU) into detoxification and methadone maintenance programs,
making use of a prospective study design to strengthen a crosssectional investigation of these conditions. To begin our
investigation, we analyzed cross-sectionally gathered data on
2879 IDUs who had been recruited through extensive
community outreach efforts and who were interviewed at the
time of recruitment. We then tested our hypotheses about
suspected determinants of entry into treatment by analyzing
prospectively gathered data on 1039 active drug users who had
no recent history of being treated for drug problems. Among
these 1039 IDUs (a subset of the initial cross-sectional sample),
144 entered a detoxification program between their recruitment
interview and their next follow-up interview, conducted about six
months after recruitment (range: 3.5-9.5 months) and 64
entered a methadone maintenance program during that
observation interval. Using multiple logistic regression analyses,
we found that a recent drug overdose, relatively higher
frequency of injecting drugs, and a history of prior arrest or
treatment were independent predictors of entry into
detoxification. Being married or living with a partner, being
female, a lengthy duration of drug use (> 10 years), and a
history of prior treatment were independent predictors of entry
into methadone maintenance. These findings shed light on what
appears to be a different profile of suspected determinants of
entry into a detoxification treatment versus methadone
maintenance treatment, and help to clarify some potential
differences between treated and untreated drug users that ought
to be considered when evaluating results of investigations with
IDU participants recruited solely from treatment settings.
PMID: 7851280 [PubMed - indexed for MEDLINE]
Symptoms discriminating between heroin addicts seeking
ambulatory detoxification or methadone maintenance.
Steer RA.
The self-report symptom inventory, SCL-90-R, was administered
to 240 heroin addicts seeking ambulatory detoxification and 240
requesting methadone maintenance. Controlling for age, a
stepwise discriminant analysis employing a backward elimination
model was performed with the SCL-90-R's nine symptom factors
to determine if the addicts described different levels of
symptomatology. Interpersonal sensitivity and depression
differentiated between the two groups; the ambulatory
detoxification patients were more depressed and described less
interpersonal sensitivity than the methadone maintenance
patients. The results supported the contention that heroin
addicts seeking ambulatory detoxification or methadone
maintenance may display different symptoms.
PMID: 7128452 [PubMed - indexed for MEDLINE]
Ability to remain abstinent after methadone detoxification. A sixyear study
B. Stimmel, J. Goldberg, E. Rotkopf and M. Cohen
Three hundred thirty-five persons successfully detoxified from methadone hydrochloride
maintenance were followed up for as long as six years to determine their ability to remain
abstinent from narcotic use. At the end of the observation period, of the 269 persons
located, 35% were narcotic-free, 58% had returned to narcotic use, and 8% were either
jailed or deceased. The ability of a person to refrain from narcotic use was found to be
highly associated with staff's assessment of progress and duration of methadone
maintenance treatment. Relapse to narcotic use occurred regardless of length of
abstinence, with 35% of relapses occurring after three or more years. While abstinence
after narcotic dependency is possible, it is not a realistic goal for all. Premature
detoxification from methadone maintenance is associated with a high recidivism rate to
narcotics.
J Subst Abuse Treat. 2000 Oct ;19 (3):301-5 11027902 (P,S,G,E,B)
Dihydrocodeine: a useful tool in the detoxification of methadonemaintained patients.
J Banbery, K Wolff, D Raistrick
Leeds Addiction Unit, 19 Springfield Mount, LS2 9NG, Leeds, UK.
We investigated the merit of dihydrocodeine tartrate for withdrawal in detoxifying 20
methadone-maintained patients presenting for treatment at the Leeds Addiction Unit
(LAU). Thirteen patients (65%) successfully completed methadone detoxification and
were abstinent from both methadone and opiate-type drugs at the end of the 2-week
program. On completion, three patients began treatment with Naltrexone and another
was abstinent at a follow-up appointment, 1 week later. A further patient relapsed
back to heroin use but remained in contact with the LAU. The remaining six patients
dropped out of the 2-week detoxification program between days 3 and 11 of the
dihydrocodeine cross-over period. We believe dihydrocodeine may have advantages
in detoxifying methadone-maintained patients.
Mesh-terms: Methadone :: administration & dosage; Adolescent; Adult; Analgesics, Opioid ::
administration & dosage; Codeine :: administration & dosage; Codeine :: analogs &
derivatives; Comparative Study; Cross-Over Studies; Dose-Response Relationship, Drug;
Drug Administration Schedule; Female; Human; Male; Opioid-Related Disorders ::
rehabilitation; Retrospective Studies; Treatment Outcome;
Other papers by authors
CKS adresse ===
http://cks.library.nhs.uk/opioid_dependence/management/quick_answers/scenario_detoxificat
ion_from_maintenance_therapy/clinical_summary_detoxification_from_methadone/detoxific
ation_from_methadone_maintenance

It is important that there is a clear distinction between maintenance and detoxification
so that the person does not slip between the two. This may occur if the reduction rate is
too slow and the person becomes unstable on the reduced dose. It is important to avoid a
situation whereby a lower level of substitute drug is reached and the user stays on this
dose long-term using illicit drugs 'on top' and therefore failing to achieve their
detoxification goals. In this situation, increase the dose of methadone until illicit drug use
has stopped, and then restart a slow reduction in methadone dose.

At the later stages of detoxification, symptomatic treatments, such as anti-diarrhoeal
medication, nonsteroidal anti-inflammatory drugs, hypnotics, or anxiolytics, may be
helpful. Advise that the person may feel withdrawal symptoms 2–3 days after stopping the
final dose (due to the long half-life of methadone).

Detoxification with buprenorphine for the final stages may be preferred. Switch to
buprenorphine when a daily dose of 30 mg methadone has been reached and the person is
stabilized (see Starting maintenance treatment with buprenorphine). Once stable on
buprenorphine, the person should remain on that dose for 2–3 days and then the dose of
buprenorphine may be reduced by 2 mg per day over 5–10 days. A more rapid
detoxification regimen should only be attempted after specialist advice.