Cochrane Database of Systematic Reviews (Reviews) || Inpatient versus other settings for...

Inpatient versus other settings for detoxification for opioid

dependence (Review)

Day E, Ison J, Strang J

This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library

2008, Issue 4

http://www.thecochranelibrary.com

Inpatient versus other settings for detoxification for opioid dependence (Review)

Copyright © 2008 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

http://www.thecochranelibrary.com

T A B L E O F C O N T E N T S

1HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

1ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

2PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

2BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

3OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

3METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

5RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

7DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

7AUTHORS’ CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

8ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

8REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

10CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

13DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

13APPENDICES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

15WHAT’S NEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

15HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

16CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

16DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

16SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

16INDEX TERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

iInpatient versus other settings for detoxification for opioid dependence (Review)


[Intervention Review]

Inpatient versus other settings for detoxification for opioiddependence

Ed Day1, Julie Ison2, John Strang3

1Department of Psychiatry, Queen Elizabeth Psychiatric Hospital, Birmingham, UK. 2Addictive Behaviours Centre, University of

Birmingham- Queen Elizabeth Psychiatric Hospital, Birmingham, UK. 3National Addiction Centre, Institute of Psychiatry, King’s

College London, London, UK

Contact address: Ed Day, Department of Psychiatry, Queen Elizabeth Psychiatric Hospital, Mindelsohn Way, Edgbaston, Birmingham,

B15 2QZ, UK. [email protected].

Editorial group: Cochrane Drugs and Alcohol Group.

Publication status and date: New search for studies and content updated (no change to conclusions), published in Issue 4, 2008.

Review content assessed as up-to-date: 24 May 2008.

Citation: Day E, Ison J, Strang J. Inpatient versus other settings for detoxification for opioid dependence. Cochrane Database of

Systematic Reviews 2005, Issue 2. Art. No.: CD004580. DOI: 10.1002/14651858.CD004580.pub2.


A B S T R A C T

Background

There are a complex range of variables that can influence the course and subjective severity of opioid withdrawal. There is a growing

evidence for the effectiveness of a range of medically-supported detoxification strategies, but little attention has been paid to the

influence of the setting in which the process takes place.

Objectives

To evaluate the effectiveness of any inpatient opioid detoxification programme when compared with all other time-limited detoxification

programmes on the level of completion of detoxification, the intensity and duration of withdrawal symptoms, the nature and incidence

of adverse effects, the level of engagement in further treatment post-detoxification, and the rates of relapse post-detoxification.

Search methods

Electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL - The Cochrane Library Issue 2, 2008); MEDLINE

(January 1966-May 2008); EMBASE (January 1988-May 2008); PsycInfo (January 1967-May 2008); CINAHL (January 1982-May

2008). In addition the Current Contents, Biological Abstracts, Science Citation Index and Social Sciences Index were searched.

Selection criteria

Randomised controlled clinical trials comparing inpatient opioid detoxification (any drug or psychosocial therapy) with other time-

limited detoxification programmes (including residential units that are not staffed 24 hours per day, day-care facilities where the patient

is not resident for 24 hours per day, and outpatient or ambulatory programmes, and using any drug or psychosocial therapy).

Data collection and analysis

All abstracts were independently inspected by two reviewers (ED & JI) and relevant papers were retrieved and assessed for methodological

quality using Cochrane Reviewers’ Handbook criteria.

1Inpatient versus other settings for detoxification for opioid dependence (Review)


mailto:[email protected]

Main results

Only one study met the inclusion criteria. This did not explicitly report the number of participants in each group that successfully

completed the detoxification process, but the published data allowed us to deduce that 7 out of 10 (70%) in the inpatient detoxification

group were opioid-free on discharge, compared with 11 out of 30 (37%) in the outpatient group. There was very limited data about

the other outcomes of interest.

Authors’ conclusions

This review demonstrates that there is no good available research to guide the clinician about the outcomes or cost-effectiveness of

inpatient or outpatient approaches to opioid detoxification.

P L A I N L A N G U A G E S U M M A R Y

Inpatient versus other settings for detoxification for opioid dependence

Dependence on opioid drugs, such as heroin, morphine, and codeine, is a serious problem in many societies. Opioids are very difficult

to quit using. The first step to quitting is detoxification, which can cause a number of painful symptoms as the drug withdraws from the

body. Many people choose an inpatient detoxification program rather than trying to stop using opioids on their own. In an inpatient

program, medications such as methadone can ease the symptoms of withdrawal and patients are in a secure, supportive environment

with no access to opiates. However, inpatient programs are expensive and can disrupt patients’ lives. An increasing number of outpatient

programs are available, providing medication and some support while keeping the drug user in the community. In addition to drop-in

programs, there are day centres and even residential facilities which are not staffed 24 hours, unlike inpatient programs. The authors

of this review looked for research comparing inpatient and other types of opiate withdrawal programs to see which is more effective.

They found only one study from 1975, which had 40 participants. The study suggested inpatient therapy might be more effective than

outpatient therapy in the short-term, but all of the inpatients relapsed within three months after detoxification. Since they found only

one outdated study which included very few patients, the Cochrane review authors could not conclude whether inpatient treatment is

more effective than outpatient or other settings. More research must be done to measure the benefits and costs of inpatient detoxification,

especially for more severely dependent users.

B A C K G R O U N D

This review is in line with a series of Cochrane reviews of the

Drug and Alcohol Review Group seeking to evaluate a variety of

different therapeutic interventions for the medical management

of the Opiate Withdrawal Syndrome in adults. Therefore much of

the background overlaps with that of other reviews (Amato 2004;

Gowing 2004a; Gowing 2004b; Gowing 2004c; Gowing 2004d)

and some is reproduced unaltered.

Dependence on opioid drugs is a major health and social issue in

most societies. Although the prevalence of opioid use is low - for

example, surveys in Australia and the European Union indicate

that up two to three per cent of the general population has ever

used opioids for non-medical purposes (AIHW 1999; EMCDDA

2002) - the burden of disease is substantial. The burden to the

individual user and the community of opioid dependence arises

from mortality (NIH 1997), which is most marked in the 15 to

34 year age group (Hall 1998), transmission of HIV and hepatitis

C, health care costs, crime and law enforcement costs (EMCDDA

2002; Healey 1998; NIH 1997), as well as the less tangible costs

of family disruption and lost productivity (Collins 1991).

The provision of treatment has a major influence on the reduction

of the harms to the individual and the community from opioid

dependence. However detoxification, or managed withdrawal, is

not in itself an adequate treatment for dependence (Lipton 1983;

Mattick 1996). Rates of completion of withdrawal tend to be low

and rates of relapse to opioid use following detoxification are high (

Milby 1988; Gossop 1989; Vaillant 1988), but withdrawal remains

a required first step for many forms of longer-term treatment (

Kleber 1982). It may also represent the end point of an extensive

period of treatment such as methadone maintenance or another

form of substitution therapy. As such, the availability of managed

withdrawal is essential to an effective treatment system.

Recent reviews have highlighted the advantages and disadvan-



tages of different medical detoxification strategies (Amato 2004;

Gowing 2004a; Gowing 2004b; Gowing 2004c; Gowing 2004d),

and in addition there is a complex range of other variables that can

influence the course and subjective severity (or intensity) of with-

drawal. This includes the type of opioid used, dose taken, dura-

tion of use, general physical health, and psychological factors such

as the reasons for undertaking withdrawal and fear of withdrawal

(Farrell 1994; Frank 1995; Milby 1986; Preston 1985). Outcomes

of a withdrawal treatment episode may also be influenced by what

happens prior to detoxification, as a period of methadone main-

tenance treatment is likely to produce a degree of stabilisation in

health and social terms that may facilitate successful withdrawal

(Backmund 2001).

Another key variable influencing likelihood of completion of

detoxification is setting. Many people with opioid dependence

have difficulty achieving abstinence in the community, citing the

proximity of drug-using friends and associates, family stressors and

lack of support. Treatment programmes delivered in residential set-

tings play an important role in the national provision of treatment

services for problem substance users in many countries through-

out the world (Gossop 1995). Both American and British na-

tional outcome studies have provided evidence of important clini-

cal improvements among clients treated in residential programmes

(Craddock 1997; Gossop 1999; Hubbard 1989; Simpson 1982).

Both have also concluded that length of time spent in treatment

is an important predictor of post-treatment outcomes. However

there is less known about the relative effectiveness of the inpatient

setting for the detoxification phase of treatment.

In the UK the national specialist inpatient drug dependence units

were established in psychiatric hospitals in the late 1960s. Inpa-

tient programmes currently provide beds in both dedicated drug

dependence units and in general psychiatric wards under the care

of drug dependence specialists. As part of a wider movement in

psychiatry in many countries bed numbers have reduced dramati-

cally since the 1950s. Thus, despite the steady increase in the size

of the opioid problem, the number of in-patient beds available

for opioid detoxification programmes has diminished broadly in

parallel with the general psychiatric beds.

During the same period the development of new techniques for

detoxification has enabled safe detoxification from heroin and

other opioid drugs in the community, and there has been a ten-

dency to view hospital-based detoxification as expensive and un-

necessary in all but the most complicated cases (DoH 1999). Out-

patient detoxification clearly has some advantages in that it does

not involve as much disruption to the patient and their family and

offers them the possibility of continuing with their normal daily

routine. It also requires them to cope with everyday situations

which they will encounter on their discharge from hospital, and

so may promote better coping skills. However, supplies of illicit

drugs are likely to be more readily available at a time when the

temptation to use will be high, possibly leading to higher relapse

rates. Furthermore medical complications of detoxification are not

as easily managed at home, and the process may have to be slower

(Kleber 1999).

A further important issue is that of cost. In simple terms detoxi-

fication in an inpatient setting appears to be much more expen-

sive. Gossop and Strang have calculated that a three-week inpa-

tient detoxification programme costs nine times more than an

eight-week outpatient programme. However, when adjustments

were made for different levels of successful outcome the costs of

inpatient and outpatient treatment are almost identical (Gossop

2000). Therefore discussion of treatment costs is misleading if not

informed by (and adjusted for) evidence of effectiveness.

This review considers the evidence for the effectiveness of the in-

patient setting as compared to non-inpatient settings for detoxifi-

cation from opioids. The primary outcome of interest is whether

the person is opioid-free at the end of the planned treatment pe-

riod, but longer term outcomes such as engagement in treatment

and relapse to opioid use will also be examined. The influence of

treatment setting upon completion of detoxification is an under-

researched area that has important clinical and financial impli-

cations for the treatment of opioid dependence. To the authors’

knowledge there has been no previous review of this topic and this

review aims to highlight any gaps in the evidence base for best

practice in this area.

O B J E C T I V E S

To evaluate the effectiveness of any inpatient opioid detoxification

programme when compared with all other time-limited detoxifi-

cation programmes on the level of completion of detoxification,

the intensity and duration of withdrawal signs and symptoms, the

nature and incidence of adverse effects experienced, the level of

engagement in further treatment post-detoxification, and the rates

of lapse and relapse post-detoxification.

M E T H O D S

Criteria for considering studies for this review

Types of studies

Randomised controlled clinical trials that compare inpatient treat-

ment (as defined below) with any form of non-residential treat-

ment.



Types of participants

All patients over the age of 18 years whose primary International

Codification of Diseases (ICD-10) or Diagnostic and Statistical

Manual of Mental Disorders (DSM-IV) diagnosis is one of opi-

oid dependence and who have undertaken a medically-supported

detoxification procedure. The impact of withdrawal from meth-

adone as compared with withdrawal from heroin was to be ex-

plored through a subgroup analysis if possible, as was the effect

of different detoxification strategies such as methadone reduction,

buprenorphine reduction, alpha-2 adrenergic agonists or symp-

tomatic treatment.

Types of interventions

(1) Experimental interventions

Inpatient opioid detoxification - any time-limited treatment for

opioid dependence where the clearly expressed aim at the outset is

detoxification (i.e. becoming opioid-free) and where the patient is

resident for 24 hours per day in a facility that also has staff present

throughout this period.

(2) Control interventions

All other time-limited detoxification programmes including

• residential units that are not staffed 24 hours per day

• day-care facilities where the patient is not resident for 24

hours per day

• outpatient or ambulatory programmes

Types of outcome measures

Primary Outcomes

(1) completion of withdrawal, as measured by self-report data and

urinary or saliva analysis

(2) intensity and duration of signs and symptoms and overall with-

drawal syndrome experienced, as measured by either objective or

self-completed measures

(3) the nature and incidence of adverse effects experienced as a

result of medication used in the detoxification procedure, as mea-

sured by either objective or self-completed measures

(4) engagement in further treatment post-detoxification, as mea-

sured by attendance at treatment sessions

(5) post-detoxification outcomes such as rates of lapse and relapse,

as measured by self-report data and urinary or saliva analysis

Secondary Outcomes

(6) cost of the treatment (where reported) in order to make com-

parisons of cost per ’completed’ detoxification between inpatient

and outpatient settings.

Search methods for identification of studies

Electronic searches

We searched Cochrane Drugs and Alcohol Group’Register of Tri-

als (March 2004), Cochrane Central Register of Controlled Trials

(CENTRAL - The Cochrane Library Issue 2, 2008), MEDLINE

(OVID - January 1966 to May 2008), EMBASE (OVID -Jan-

uary 1988 to May 2008), PsycInfo (OVID -January 1967 to May

2008), CINAHL (OVID -January 1982 to May 2008). To iden-

tify studies included in this review, we used detailed search strate-

gies for each database searched to take account of differences in

controlled vocabulary and syntax rules, see Appendix 1; Appendix

2; Appendix 3; Appendix 4; Appendix 5; Appendix 6.

In addition the Current Contents, Biological Abstracts, Science

Citation Index and Social Sciences Index were searched.

Searching other resources

We handsearched the reference lists of retrieved studies, reviews

and conference abstracts. We contacted authors of included studies

and experts in the field wherever possible to find out if they knew

of any other published or unpublished controlled trials assessing

the effectiveness of opioid detoxification in different treatment

settings.

All searches included non-English language literature. Those stud-

ies with English abstracts were assessed for inclusion on the basis of

the abstract. No non-English language abstracts were considered

to meet inclusion criteria.

Data collection and analysis

Selection of studies

Two independent authors (ED, JI) undertook a systematic exam-

ination of all references retrieved by the search. The two authors

independently selected trials assessing the effectiveness of opioid

detoxification in different treatment settings.

Data extraction and management

Two authors (ED and JI) independently extracted data. Any dis-

agreement was discussed and the decisions documented. Where

necessary, we contacted the authors of the studies to help resolve

the issue.

The summary statistics required for each trial and each outcome for

continuous data were the mean change from baseline, the standard

error of the mean change, and the number of patients for each

treatment group at each assessment. Where changes from baseline

were not reported, the mean, standard deviation and the number of

patients for each treatment group at each time point was extracted.

For binary data the numbers in each treatment group and the

numbers experiencing the outcome of interest were sought. The

baseline assessment was defined as the latest available assessment

prior to randomization, but no longer than two months prior.



For each outcome measure, we sought data on every participant as-

sessed. To allow an intention-to-treat analysis, the data was sought

irrespective of compliance, whether or not the patient was subse-

quently deemed ineligible, or otherwise excluded from treatment

or follow-up. If intention-to-treat data were not available in the

publications, “on-treatment” or the data of those who completed

the trial were sought and indicated as such.

Assessment of risk of bias in included studies

The quality of the methodology of each selected trial was be

examined with reference to Cochrane Collaboration guidelines

(Alderson 2004) on the basis of the method of allocation conceal-

ment and was rated as follows:

A. Low risk of bias: adequate allocation concealment, i.e. central

randomisation (e.g. allocation by a central office unaware of par-

ticipant characteristics), computer file that can be accessed only af-

ter the characteristics of an enrolled participant have been entered

or other description containing elements suggesting adequate con-

cealment.

B. Moderate risk of bias: unclear allocation concealment, in which

the authors either did not report an allocation concealment ap-

proach at all or report an approach that did not fall in the category

A or C.

C. High risk of bias: inadequate allocation concealment, such as

alternation or reference to case numbers or dates of birth.

D. When allocation concealment has not been used to evaluate

the quality of the study (i.e when it does not apply because of a

study design other than RCT).

Methodological quality was not used as a criterion for inclusion in

the review, but its impact is considered in the discussion section.

Measures of treatment effect

The RevMan software package was to be used to perform the meta-

analysis for continuous and dichotomous outcome measures, al-

though ultimately the data available did not allow such an analysis.

We aimed to analyse both the pooled data and by patient subgroup:

• Type of detoxification setting (eg inpatient, day care,

outpatient)

• Type of medication used (eg methadone reduction, alpha-2

agonists)

Furthermore we also aimed to analyse data by:

• Drug of dependence - heroin or methadone

• Poly-drug use - the effects of use of alcohol and other drugs

• Concurrent physical & psychiatric illness

• Time to outcome measure - short-term (up to one month),

medium term (one month up to six months) and long-term

(longer than six months)

Data synthesis

As only one study met the inclusion criteria, no meta-analysis was

performed.

R E S U L T S

Description of studies

See: Characteristics of included studies; Characteristics of excluded

studies.

(1) Excluded studies

One study was identified from the abstract as potentially suitable (

Vidjak 2003) in that it involved a systematic allocation of 90 heroin

addicts to either methadone, hospital, or therapeutic community

treatment. However, on analysis of the paper it became clear that

the study was retrospective and did not involve randomisation.

In a second study (Gossop 1986) the 60 participants (45 men and

15 women) were all patients of a Drug Dependence Clinic, and

most (47, 78%) were primarily dependent on heroin. They were

assigned the participants to one of four groups: the randomised

outpatient group, the randomised inpatient group, the preferred

outpatient group, and the preferred inpatient group. All partic-

ipants were asked if they were prepared to accept either inpa-

tient or outpatient withdrawal. Those subjects who were willing

to accept either were then assigned to one of the two randomised

groups. Those who expressed a strong preference for inpatient or

outpatient withdrawal were assigned to the appropriate preference

group.

The inpatient treatment programme lasted for 21 days. The out-

patient programme lasted for 56 days and entailed weekly atten-

dance at the clinic for counselling. Both withdrawal schemes used

oral methadone, the dose of which was reduced on a daily basis

using a linear (equal dose) reduction model. The principal aim

was to achieve abstinence at the end of the supervised withdrawal

regime, and abstinence was confirmed by urine analysis. A total

of 25 (81%) of the 31 participants in the inpatient withdrawal

group were successfully withdrawn from opioid drugs (and all

other drugs, including alcohol), whereas only 5 (17%) of the 29

participants in the outpatient withdrawal group achieved absti-

nence. However, only 20 of the total sample of 60 were actually

randomised, and although the authors comment on ’the complete

failure of the randomised outpatient group’, the number of partic-

ipants actually randomised to inpatient or outpatient treatment is

not reported. The study was therefore excluded from the review.

(2) Included studies

Only one study was identified that met the inclusion criteria for

the review (Wilson 1975).

(a) Participants

In Wilson 1975 the participants were all physically dependent

on heroin and had pharmacological evidence of current drug use



through urinalysis or clinical evidence of the opioid withdrawal

syndrome. The 40 participants had a mean age of 22 years, and

although the sex ratio is not reported the authors comment that

the group ’tended to be white, single and male’. For nearly 75%

of the sample this was the first withdrawal treatment experience.

(b) Interventions

Wilson 1975 randomly assigned participants to hospital detoxi-

fication or outpatient detoxification. The hospital detoxification

group was supervised by three psychiatrists on an open ward of

an acute psychiatric treatment service in a general hospital. The

detoxification was performed using methadone, although exact

details of the process are not reported beyond that the psychiatrists

used ’their usual narcotic detoxification procedure with the single

limitation that dosage of methadone would not exceed 40mg in

any 24-hour period’. No prescribed length of treatment was im-

posed on the hospital participants, and those who felt stabilised

or requested to leave were discharged. Participants were expected

to participate in ward activities and group meetings. The outpa-

tient detoxification group also received methadone, and were su-

pervised by one psychiatrist. All methadone doses were given un-

der the direct supervision of the clinic nurse, and the procedure

occurred in a fixed 10-day period. Withdrawal was accomplished

by starting with a flexible dose of 10-20mg of methadone and

stabilising at a maximum of 40mg daily on day 2-3. Dosage was

then individualised, but no more than 30mg of methadone was

administered on days 4 or 5, no more than 20mg on days 6 or

7, and no more than 10mg on days 8, 9, or 10. All participants

were offered individual counselling by the psychiatrist and clinic

nurses. Both groups were also offered supportive medication as

clinically indicated.

(c) Outcomes

Wilson 1975 reported drug use during treatment (as measured by

self-report and urine analysis) and the length of the heroin-free

period after detoxification treatment. The authors also reported

the average cost of both treatment modalities.

Risk of bias in included studies

(1) Randomization

Wilson 1975 reported randomly allocating participants to differ-

ent treatment modalities, but did not describe the method used

to generate random allocation. Furthermore, significant method-

ological problems surrounding randomisation were identified.

The authors reported randomly allocating patients accepted for

treatment to either hospital or outpatient detoxification, but also

that some patients refused treatment rather than accept hospitali-

sation. This may explain why 30 of the 40 study participants were

in the outpatient treatment group and only 10 were in the inpa-

tient group.

(2) Blinding

Wilson 1975 did not report that staff collecting or analysing the

outcome data were blinded to the participants’ treatment modality.

(3) Losses to follow up

Although it is not explicitly reported, it would appear that approx-

imately 20 participants dropped out of the Wilson 1975 study

after randomisation and prior to starting inpatient treatment. If

this was the case, the results are not reported on an intention-to-

treat basis and are therefore likely to be biased in favour of inpa-

tient treatment. As the exact number of dropouts is not reported,

it would not be appropriate to subject the study to further quan-

titative analysis.

Effects of interventions

(1) Completion of withdrawal, as measured by self-report data

and urinary or saliva analysis

The Wilson 1975 study does not explicitly report the number of

participants in each group that successfully completed the detoxi-

fication process. The authors reported data about relapse to heroin

use after detoxification treatment, and from this it is possible to de-

duce that 7 out of 10 (70%) in the inpatient detoxification group

were opioid-free on discharge, compared with 11 out of 30 (37%)

in the outpatient group. However a number of participants also

refused treatment rather than accepting hospitalisation (although

the exact number is not reported), and so the completion rate

in the inpatient sample calculated on an intention-to-treat basis

would certainly have been much lower.

(2) Intensity and duration of signs and symptoms and overall

withdrawal syndrome experienced, as measured by either ob-

jective or self-completed measures

The included study (Wilson 1975) did not report the effect of the

intervention on these outcomes.

(3) The nature and incidence of adverse effects experienced as

a result of medication used in the detoxification procedure, as

measured by either objective or self-completed measures



(4) Engagement in further treatment post-detoxification, as

measured by attendance at treatment sessions



(5) Post-detoxification outcomes such as rates of lapse and

relapse, as measured by self-report data and urinary or saliva

analysis

The Wilson 1975 study mentioned levels of treatment attendance

after the detoxification period, although this was not specified as an

outcome measure at the outset of the study. Three out of 10 (30%)

in the hospital sample were lost to follow-up. Of the remaining

seven, one resumed heroin use within 24 hours of discharge, one

within one week, two within one month, two within two months,



and one within three months. In the outpatient sample 10 (33%)

of the participants were lost to follow-up, and one patient assigned

to the group did not initiate treatment. A further eight (27%) never

stopped using heroin despite receiving methadone. Two reported

return to heroin use within one week of treatment, five within

two months, and one resumed without specifying the time period.

Two participants were still heroin-free when last contacted two

months after treatment. Unfortunately the authors did nor report

the frequency of contact with the participants in the follow-up

period, and the method of determining relapse to heroin (urinary

analysis or self-report) is not specified.

(6) The Cost of Treatment

Wilson 1975 reported the average cost of treatment in the outpa-

tient group as US$10 per day or US$100 for a 10-day detoxifica-

tion programme (including the cost of intake procedures, labora-

tory work and medications). The average cost of the hospital treat-

ment was US$91 per day or US$496 for a treatment programme

with an average patient stay of 5.4 days.

D I S C U S S I O N

Inpatient detoxification is an expensive process requiring consid-

erable resources, and therefore it is surprising that so few clinical

studies have examined its effectiveness. Both studies produced by

the literature searching process were small and had methodolog-

ical limitations, and only one met the inclusion criteria for the

review. Both made use of methadone reduction as a detoxification

method, and newer techniques are now available that have gener-

ally increased opioid detoxification rates in the community setting

(Akhurst 1999). Neither study reports longer-term outcomes in

any detail, so it is difficult to determine whether inpatient detox-

ification has other benefits.

Non-randomised studies comparing inpatients and outpatients

typically show that the former have more severe substance use his-

tories and a greater prevalence of medical, psychosocial and voca-

tional difficulties, including less social stability, more unemploy-

ment and a greater preponderance of medical and psychiatric disor-

ders (DoH 1996). However, these data reflect referral patterns and

not which populations fare best in each setting. Inpatient detoxifi-

cation is generally considered to be indicated for those individuals

who have too many adverse prognostic features to be successful at

detoxification as an outpatient (DoH 1999). In practice, not only

are such individuals also the least likely to complete detoxification

as an inpatient, but they are often especially unable to tolerate

the constraints of a hospital setting. This has been described as

the ’severity paradox’, in which success is unlikely in those who

are particularly considered to require the approach (Seivewright

2000), and is likely to have arisen due to economic restraints rather

than clinical evidence. Despite evidence that inpatient provision

for drug detoxification is diminishing (Mark 2002), this review

suggests that practice in the field continues to be lead by clinical

experience and intuition rather than evidence.

A U T H O R S ’ C O N C L U S I O N S

Implications for practice

There is a lack of good quality research evidence available to guide

practice in this area. Detoxification is an essential first step in

achieving lifelong abstinence, but little attention has been paid to

the effect of treatment setting (Mattick 1996). Given the potential

cost of inpatient treatment, it is perhaps surprising that a search

of the world literature in this area yielded only two randomised

controlled trials, both with significant methodological limitations.

The only real conclusion that can be drawn is that there is very

little available research to guide the clinician about the longer-

term outcomes or cost-effectiveness of inpatient or outpatient ap-

proaches.

Implications for research

Reviews in the alcohol research field have concluded that there is

no evidence for the superiority of inpatient over outpatient treat-

ment of alcohol abuse (Miller 1986). However, extrapolation of

these results to the treatment of other substance users must be

done with caution, and better designed research is needed to con-

firm this conclusion for opioid dependent individuals. The ran-

domised controlled trial is usually the methodology of choice for

determining which treatment option is best. However, in the case

of inpatient opioid detoxification there is a problem of equipoise,

whereby the patients who theoretically might benefit most from

the treatment are often excluded from randomised trials. Patients

with opioid dependence and co-existing mental illness, severe so-

cial isolation or dependence on other substances are often consid-

ered too unwell to attempt detoxification anywhere else other than

an inpatient setting. Therefore they are often excluded from clin-

ical trials, and this is likely to reduce any possible advantages that

treatment in an in-patient setting may convey (Finney 1996). Fur-

thermore, the few studies that have looked at the effect of setting

on detoxification outcomes have involved too few participants to

provide sufficient statistical power to detect potential differences.

It is important to remember that a failure to detect a difference

in these circumstances is not the same as proving that no benefit

exists.

From a clinician’s perspective there is a small group of patients who

will benefit from undertaking detoxification in more supportive

settings. Therefore, one profitable research strategy may be to de-

velop good quality prospective studies to look at the outcomes of

patients with complex problems after inpatient admission. This

would allow the testing of hypotheses concerning predictive fac-

tors for good treatment outcomes in particular populations (e.g.



people with a co-existing severe mental illness, people dependent

on more than one substance). There is also some evidence that

detoxification in an inpatient environment may increase the like-

lihood of engaging the patient in longer term care (Ghodse 2002),

and such a prospective cohort study would be suitable for exam-

ining such issues.

A C K N O W L E D G E M E N T S

None

R E F E R E N C E S

References to studies included in this review

Wilson 1975 {published data only}∗ Wilson BK, Elms RR, Thomson CP. Outpatient versus

hospital methadone detoxification: An experimental

comparison. International Journal of the Addictions 1975;10

(1):13–21.

References to studies excluded from this review

Gossop 1986 {published data only}

Gossop M, Johns A, Green L. Opiate withdrawal: inpatient

versus outpatient programmes and preferred versus random

assignment to treatment. British Medical Journal 1986;293

(6539):103–4.

Vidjak 2003 {published data only}

Vidjak N. Treating heroin addiction: comparison of

methadone therapy, hospital therapy without methadone,

and therapeutic community. Croatian Medical Journal

2003;44(1):59–64.

Additional references

AIHW 1999

Australian Institute of Health & Welfare. 1998 National

Drug Strategy Household Survey: First Results. Canberra:

AIHW, 1999.

Akhurst 1999

Akhurst JS. The use of lofexidine by drug dependency units

in the United Kingdom. European Addiction Research 1999;

5(1):43–9.

Alderson 2004

Alderson P, Green S, Higgins JPT, editors. Cochrane

Reviewers’s Handbook 4.2.2 [updated March 2004].

In: The Cochane Library [database on CDROM]. The

Cochrane Collaboration. Chichester, UK: John Wiley &

Sons, Ltd; 2004..

Amato 2004

Amato L, Davoli M, Ferri M, Ali R. Methadone at tapered

doses for the management of opioid withdrawal. Cochrane

Database of Systematic Reviews 2004, Issue 3. [DOI:

10.1002/14651858]

Backmund 2001

Backmund M, Meyer K, Eichenlaub D, Schutz CG.

Predictors for completing an inpatient detoxification

program among intravenous heroin users, methadone

substituted and codeine substituted patients. Drug and

Alcohol Dependence 2001;64:173–80.

Collins 1991

Collins DJ, Lapsley HM. Estimating the economic costs of

drug abuse in Australia. Canberra: Australian Government

Publishing Service, 1991.

Craddock 1997

Craddock SG, Rounds-Bryant JL, Flynn PM, Hubbard

RL. Characteristics and pre-treatment behaviours of clients

entering drug abuse treatment 1969-1993. American

Journal of Drug and Alcohol Dependence 1997;23(1):43–59.

DoH 1996

Department of Health. Task Force to Review Services for

Drug Misuers. London: Department of Health, 1996.

DoH 1999

Department of Health. Drug Misuse and Dependence

- Guidelines on Clinical Management. Norwich: The

Stationery Office, 1999.

DSM-IV

American Psychiatric Association (Pub.). Diagnostic and

Statistical Manual of Mental Disorders DSM-IV-TM.

Washington DC: American psychiatric association, 1994.

EMCDDA 2002

European Monitoring Centre for Drugs and Drug

Addiction. Annual report on the state of the drugs problem in

the European Union and Norway. Luxembourg: Office for

Official Publications of the European Communities, 2002.

Farrell 1994

Farrell M. Opiate withdrawal. Addiction 1994;89(11):

1471–5.



Finney 1996

Finney JW, Hahn AC, Moos RH. The effectiveness of

inpatient and outpatient treatment for alcohol abuse: the

need to focus on mediators and moderators of setting

effects. Addiction 1996;91(12):1773–96.

Frank 1995

Frank L, Pead J. New concepts in drug withdrawal: a resource

handbook. Melbourne: University of Melbourne, 1995.

Ghodse 2002

Ghodse AH, Reynolds M, Baldacchino AM, Dunmore E,

Byrne S, Oyefeso A, et al.Treating an opiate-dependent

inpatient population: A one-year follow-up study of

treatment completers and non-completers. Addictive

Behaviours 2002;27:765–78.

Gossop 1989

Gossop M, Green L, Phillips G, Bradley B. Lapse, relapse

and survival among opiate addicts after treatment. A

prospective follow-up study. British Journal of Psychiatry

1989;154:348–53.

Gossop 1995

Gossop M. The treatment mapping survey: a descriptive

study of drug and alcohol treatment responses in 23

countries. Drug and Alcohol Dependence 1995;39:7–14.

Gossop 1999

Gossop M, Marsden J, Stewart D, Rolfe A. Treatment

retention and 1 year outcomes for residential programmes

in England. Drug and Alcohol Dependence 1999;57:89–98.

Gossop 2000

Gossop M, Strang J. Price, cost and value of opiate

detoxification treatments. Reanalysis of data from two

randomised trials. British Journal of Psychiatry 2000;177:

262–6.

Gowing 2004a

Gowing L, Farrell M, Ali R, White J. Alpha2 adrenergic

agonists for the management of opioid withdrawal.

Cochrane Database of Systematic Reviews 2004, Issue 3.

[DOI: 10.1002/14651858]

Gowing 2004b

Gowing L, Ali R, White J. Buprenorphine for the

management of opioid withdrawal. Cochrane Database

of Systematic Reviews 2004, Issue 3. [DOI: 10.1002/

14651858]

Gowing 2004c

Gowing L, Ali R, White J. Opioid antagonists with

minimal sedation for opioid withdrawal. Cochrane Database

of Systematic Reviews 2004, Issue 3. [DOI: 10.1002/

14651858]

Gowing 2004d

Gowing L, Ali R, White J. Opioid antagonists under heavy

sedation or anaesthesia for opioid withdrawal. Cochrane

Database of Systematic Reviews 2004, Issue 3. [DOI:

10.1002/14651858]

Hall 1998

Hall W, Darke S. Trends in opiate overdose deaths in

Australia 1979-1995. Drug and Alcohol Dependence 1998;

52:71–7.

Healey 1998

Healey A, Knapp M, Astin J, Gossop M, Marsden J, Stewart

D, et al.Economic burden of drug dependency. Social costs

incurred by drug users at intake to the National Treatment

Outcome Research Study. British Journal of Psychiatry 1998;

173:160–5.

Hubbard 1989

Hubbard RL, Marsden ME, Rachal JV, Chapel Hill, 1989.

Drug Abuse Treatment: A National Study of Effectiveness.

Chapel Hill: University of North Carolina Press, 1989.

Kleber 1982

Kleber HD, Riordan CE. The treatment of narcotic

withdrawal: a historical review. Journal of Clinical Psychiatry

1982;43(6):30–4.

Kleber 1999

Kleber HD. Opioids: Detoxification. In: Galanter M,

Kleber HD editor(s). Textbook of Substance Abuse Treatment.

Washington DC: American Psychiatric Press, 1999:251–69.

Lipton 1983

Lipton D, Maranda M. Detoxification from heroin

dependency: An overview of method and effectiveness.

Advances in Alcohol and Substance Abuse 1983;2(1):31–55.

Mark 2002

Mark TL, Dilonardo JD, Chalk M, Coffey RM. Trends in

inpatient detoxification services. Journal of Substance Abuse

Treatment 2002;23:253–60.

Mattick 1996

Mattick RP, Hall W. Are detoxification programmes

effective?. Lancet 1996;347:97–100.

Milby 1986

Milby JB, Gurwitch RH, Wiebe DJ, Ling W, McLellan

AT, Woody GE. Prevalence and diagnostic reliability of

methadone maintenance detoxification fear. American

Journal of Psychiatry 1986;143(6):739–43.

Milby 1988

Milby J. Methadone maintenance to abstinence. How

many make it?. The Journal of Nervous and Mental Disease

1988;176(7):409–22.

Miller 1986

Miller WR, Hester RK. Inpatient alcoholism treatment:

Who benefits?. American Psychologist 1986;41(7):794–805.

NIH 1997

NIH Consensus Development Statement. Effective Medical

Treatment of Opiate Addiction. National Institutes of

Health, 1997.

Preston 1985

Preston KL, Bigelow GE. Pharmacological advances in

addiction treatment. International Journal of the Addictions

1985;20(6&7):845–67.



Seivewright 2000

Seivewright N. Community Treatment of Drug Misuse: More

Than Methadone. Cambridge: Cambridge University Press,

2000.

Simpson 1982

Simpson DD, Sells SB. Effectiveness for treatment of drug

abuse: an overview of the DARP research programme.

Advances in Alcohol and Substance Abuse 1982;2(1):7–29.

Vaillant 1988

Vaillant GE. What can long-term follow-up teach us about

relapse and prevention of relapse in addiction?. British

Journal of Addiction 1988;83(10):1147–57.∗ Indicates the major publication for the study



C H A R A C T E R I S T I C S O F S T U D I E S

Characteristics of included studies [ordered by study ID]

Wilson 1975

Methods Participants accepted for treatment were randomly assigned to hospital detoxification (HD) or outpatient

detoxification (OPD). The hospital unit was an open ward of an acute psychiatric treatment service in a

general hospital

Participants 40 participants

Over 18 years old (mean age 22 years)

Seeking narcotic (heroin) detoxification

Criteria for admission to treatment included evidence of physical dependence on narcotics and pharma-

cological evidence of current drug use through urinalysis or clinical evidence of the narcotic withdrawal

syndrome

33% were employed

40% were living with their parents

Interventions (1) Hospital detoxification - supervised by 3 psychiatrists and followed their normal detoxification proce-

dure with the single limitation that dosage of methadone would not exceed 40mg in any 24-hour period.

No prescribed length of treatment was imposed, and patients who felt stabilized or requested to leave were

discharged.

(2) Outpatient detoxification - supervised by 1 psychiatrist. Detoxification was accomplished in a 10 day

period by starting with a flexible dose of 10 to 20mg of methadone and stabilizing at a maximum dose of

40mg daily on the second or third day of treatment. Dosage was individualized, but no more than 30mg

of methadone was administered on days 4 or 5, no more than 20mg on days 6 or 7, and no more than

10mg on days 8,9, or 10.

All participants were offered individual counselling by the psychiatrist and clinic nurses.

Both groups were offered supportive medication as clinically indicated

Outcomes Hospital detoxification - 7 out of 10 (70%) subjects were drug free at the end of the detoxification period

Outpatient detoxification - 11 out of 30 (37%) participants were drug free at the end of the detoxification

period

One third of both groups were lost to follow-up.

All hospital detoxification patients had returned to heroin use within 3 months of treatment

All but two of the outpatient detoxification patients had returned to heroin use within 2 months of

treatment, and one of these was in prison

Notes Some patients refused treatment rather than accept hospitalisation. Ten patients were assigned to HD and

30 patients to OPD, suggesting that about 20 patients dropped out of the HD group

Risk of bias

Item Authors’ judgement Description

Allocation concealment? Unclear B - Unclear



Characteristics of excluded studies [ordered by study ID]

Study Reason for exclusion

Gossop 1986 60 participants (45 men, 15 women), all physically dependent on opiates and asking to be withdrawn.

Participants were asked if they were prepared to accept either inpatient or outpatient opiate withdrawal, and those

who were willing to do so were assigned randomly to the randomised inpatient or randomised outpatient group.

Those who expressed a strong preference were assigned to the preferred outpatient or preferred inpatient group.

It is not possible to calculate from the paper the number of participants who completed in the randomised inpatient

or randomised outpatient group

Vidjak 2003 Not a randomised controlled trial, but rather a post-treatment construction of three samples



D A T A A N D A N A L Y S E S

This review has no analyses.

A P P E N D I C E S

Appendix 1. Cochrane Drugs and Alcohol Group’Register of Trials search strategy

diagnosis=opioid and intervention=setting

Appendix 2. CENTRAL search strategy

1. substance-related disorders:ME

2. Opiod-related disorders:ME

3. #1 or #2

4. addict*

5. abus*

6. use*

7. addict*

8. disorder*

9. #4 or #5 or #6 or #7 or #8

10. SUBSTANCE WITHDRAWAL SYNDROME:ME

11. Detoxification

12. #10 or #11

13. opiat*

14. opioid*

15. diacetylmorphine

16. morphin*

17. HEROIN

18#13 OR #14 OR #15 OR #16 or #17

19. INPATIENTS:ME

20. OUTPATIENTS:ME

21. HOSPITALIZATION:ME

22. hospital*

23. inpatient*

24. #19 OR #20 OR #21 OR #22 OR #23

25. #9 AND #18 AND #24



Appendix 3. MEDLINE search strategy

1. exp substance-related disorders/

2. opiod-related disorders/

3. (addict$ or abus$ or use$).ab,ti

4. 1 or 2 or 3

5. (morphine.ab,ti or opioid$ or opiate*or heroin).ab,ti

6. exp heroin/

7. 5 or 6

8. exp Inpatients/

9. exp Outpatients/

10. exp Hospitals

11. hospital$.ab,ti

12. inpatient$.ab,ti

13. setting.mp

14. 8 or 9 or 10 or 11 or 12 or 13

15. 4 and 7

16. 14 and 15

17. limit 15 to human

Appendix 4. EMBASE search strategy

1. exp narcotic dependence/

2. (addict$ or abus$ or use$).ab,ti

3. 1 or 2

4. exp Withdrawal syndrome/

5. exp Drug detoxification/

6. detoxification.ab,ti

7. 4 or 5 or 6

8. exp morphine derivative

9. morphine.ab,ti

10. exp diamorphine/

11. exp opiate/

12. opioid.ab,ti

13. 8 or 9 or 10 or 11 or 12

14. exp Hospital Patient/

15. exp Outpatient/

16. Inpatient.ab,ti

17. setting*.ab,ti

18. 14 or 15 or 16 or 17


Appendix 5. PsycInfo search strategy

1. exp drug addiction

2. (addict$ or abus$ or dependen$).ti,ab,sh.

3. 1 or 2

4. exp detoxification/

5. 3 or 4

6. exp morphine/

7. exp heroin/

8. exp opiates/



9. opioid$.ab,ti

10. 6 or 7 or 8 or 9

11. inpatient.ab,ti

12. exp outpatient treatment/

13. exp Hospitals/

14. setting.ab,ti

15. 11 or 12 or 13 or 14

16. 5 and 10

17. 15 and 16


Appendix 6. CINAHL search strategy

1. exp Substance abuse/

2. exp Substance dependence/

3. (addict$ or abus$ or dependen$).ti,ab,sh.

4. 1 or 2 or 3

5. detoxification

6. exp Substance Withdrawal Syndrome

7. 5 or 6

8. exp opium/

9. (opioid$ or heroin or morphine).ab,ti

10. 8 or 9

11. exp Inpatient/

12. exp Hospitals/

13. setting.ab,ti

14. 11 or 12 or 13

15. 7 and 10

16. 14 and 15


W H A T ’ S N E W

Last assessed as up-to-date: 24 May 2008.

Date Event Description

26 May 2008 New search has been performed new search, no new trials

25 March 2008 Amended Converted to new review format.



H I S T O R Y

Protocol first published: Issue 1, 2004

Review first published: Issue 2, 2005

Date Event Description

4 January 2005 New citation required and conclusions have changed Substantive amendment

C O N T R I B U T I O N S O F A U T H O R S

Two independent reviewers (ED, JI) undertook a systematic examination of all references retrieved by the search. The two reviewers

(ED, JI) independently selected trials assessing the effectiveness of opioid detoxification in different treatment settings, did the quality

assessment and wrote the review. JS supervising and commented on the draft .

D E C L A R A T I O N S O F I N T E R E S T

Two of the authors (ED, JS) have clinical responsibilities for clinical services that provide opioid detoxification in both inpatient and

outpatient settings.

S O U R C E S O F S U P P O R T

Internal sources

• Birmingham and Solihull Mental Health NHS Trust, UK.

External sources

• No sources of support supplied

I N D E X T E R M S

Medical Subject Headings (MeSH)

∗Hospitalization; Methadone [therapeutic use]; Narcotics [therapeutic use]; Opioid-Related Disorders [∗rehabilitation]



MeSH check words

Humans



Date post:	09-Dec-2016
Category:	Documents
Upload:	ed
View:	216 times
Download:	1 times

Cochrane Database of Systematic Reviews (Reviews) || Inpatient versus other settings for...

Documents