Methadone at tapered doses for the management of opioid withdrawal

Despite widespread use in many countries of tapered methadone for detoxification from opiate dependence, the evidence of efficacy to prevent relapse and promote lifestyle change has not been systematically evaluated.

To determine whether tapered methadone is effective to manage withdrawal from opioids.

We searched: the Cochrane Controlled Trials Register (Issue 1, 2000), MEDLINE (OVID 1966-2000), EMBASE (1980-2000); scan of reference list of relevant articles; personal communication; conference abstracts; unpublished trials from pharmaceutical industry; Internet (NIDA, Clinical Trials.org, BMJ).

All randomised controlled trials which focus on the use of tapered methadone (length of treatment max 30 days) versus all other pharmacological detoxification treatments, placebo and different modalities of methadone detoxification programs for the treatment of opiate withdrawal. Trials including patients with additional diagnoses such as benzodiazepine dependence were also eligible.

One reviewer (LA) assessed studies for inclusion and undertook data extraction. Inclusion decisions and the overall process were confirmed by consultation between reviewers. Qualitative assessments of the methodology of eligible studies were carried out using validated checklists. Where possible analysis was carried out according to the "intention to treat" principles.

20 studies were included in the review, with 1357 people randomised. 10 studies compared methadone with adrenergic agonists, 7 studies compared different modalities of methadone detoxification, 2 studies compared methadone with other opioid agonists, 1 study compared methadone with chlordiazepoxide one with placebo. The conclusions of the 10 studies that compared methadone with adrenergic agonists showed a substantial clinical difference of the two treatments in terms of retention in treatment, degree of discomfort and detoxification success rates. The conclusions of the 6 studies that compare different methadone reduction schedules, showed that different types of methadone withdrawal schedule produce different responses in terms of time course of withdrawal, the severity of withdrawal response and possibly in terms of subsequent engagement with treatment. Regarding the studies that compare methadone with other opioid agonists, in Sorensen 1982 methadyl acetate performed similarly to methadone on most process and outcome measures, while in Tennant 1975, methadone reduced severity of withdrawal and had fewer drop-outs than did a propoxyphene group. In Drummond 1989, using chlordiazepoxide vs methadone, the results suggest that the two drugs had similar results in terms of overall effectiveness. San 1992 compared methadone with placebo and found more severe withdrawal and more drop outs in the placebo group. The results indicate that tapered methadone and other medications used in the included studies are effective in the treatment of the heroin withdrawal syndrome, although symptoms experienced by subjects differed according to the medication used and the program adopted. It seems that regardless of which medication is selected for heroin detoxification, the rates of subsequent heroin abstinence are about equal. This suggests that the medications are similar in terms of overall effectiveness. Improvements were achieved when other services such as counseling and other supporting services were offered contemporaneously with detoxification.

Data from literature are hardly comparable; programs vary widely with regard to duration, design and treatment objectives, impairing the application of meta-analysis. Results of many outcomes could not be summarised because they were presented either in graphical form or provided only statistical tests and p-values. For most studies standard deviation for continuous variables were not provided. The studies included in this review confirm that slow tapering with temporary substitution of long acting opioids, accompanied by medical supervision and ancillary medications can reduce withdrawal severity. Nevertheless the majority of patients relapsed to heroin use. However this cannot be considered a goal for a detoxification as heroin dependence is a chronic, relapsing disorder and the goal of detoxification should be to remove or reduce dependence on heroin in a controlled and human fashion and not a treatment for heroin dependence.