Buprenorphine for the management of opioid withdrawal

L Gowing, R Ali, J White
Cochrane Database of Systematic Reviews 2004, (4): CD002025

BACKGROUND: Managed withdrawal (detoxification) is a necessary step prior to drug-free treatment. It may also represent the end point of long-term opioid replacement treatment such as methadone maintenance. The availability of managed withdrawal is essential to an effective treatment system.

OBJECTIVES: To assess the effectiveness of interventions involving the use of buprenorphine to manage opioid withdrawal, in terms of withdrawal signs and symptoms, completion of withdrawal and adverse effects.

SEARCH STRATEGY: Multiple electronic databases (including Medline, Embase, PsycINFO, Australian Medical Index, Cochrane Clinical Trials Register) were systematically searched to October 2003. Reference lists of retrieved studies, reviews and conference abstracts were handsearched.

SELECTION CRITERIA: Controlled trials comparing buprenorphine with reducing doses of methadone, alpha2 adrenergic agonists, symptomatic medications or placebo, or comparing different buprenorphine-based regimes, to modify the signs and symptoms of withdrawal in participants who were primarily opioid dependent.

DATA COLLECTION AND ANALYSIS: One reviewer assessed studies for inclusion and undertook data extraction. Inclusion decisions and the overall process were confirmed by consultation between all three reviewers. Included studies were assessed for methodological quality. Meta-analysis was undertaken where possible, with sensitivity analyses used to assess the impact of methodological quality.

MAIN RESULTS: Thirteen studies (10 RCTs), involving 744 participants, met the criteria for inclusion in the review. Seven studies compared buprenorphine with clonidine; 3 compared buprenorphine with methadone; 1 compared buprenorphine with oxazepam; 2 compared rapid and slow rates of tapering buprenorphine dose; 1 compared 3 different starting doses of buprenorphine. For groups treated with buprenorphine, withdrawal severity was less than that in groups treated with clonidine; peak severity was similar to those treated with methadone, but withdrawal symptoms may resolve more quickly with buprenorphine. Withdrawal is probably more severe when doses are tapered rapidly following a period of maintenance treatment. Buprenorphine is associated with fewer adverse effects than clonidine, and completion of withdrawal is significantly more likely with buprenorphine (Relative Risk 1.35, 95% confidence interval 1.13, 1.62). In the two available studies, there was no statistically significant difference in rates of completion of withdrawal for buprenorphine compared to methadone in reducing doses. Completion of withdrawal following buprenorphine maintenance treatment may be more likely when doses are reduced gradually.

REVIEWERS' CONCLUSIONS: Buprenorphine is more effective than clonidine for the management of opioid withdrawal. There appears to be no significant difference between buprenorphine and methadone in terms of completion of withdrawal, but withdrawal symptoms may resolve more quickly with buprenorphine. Many aspects of treatment protocol and relative effectiveness need to be investigated further in order to determine the most effective way of using buprenorphine to manage opioid withdrawal.

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