Buprenorphine for the management of opioid withdrawal

Cochrane Database Syst Rev. 2009 Jul 8;(3):CD002025. doi: 10.1002/14651858.CD002025.pub4.


Background: Managed withdrawal is a necessary step prior to drug-free treatment or as the end point of substitution treatment.

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

Search strategy: We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 3, 2008), MEDLINE (January 1966 to July 2008), EMBASE (January 1985 to 2008 Week 31), PsycINFO (1967 to 7 August 2008) and reference lists of articles.

Selection criteria: Randomised controlled trials of interventions involving the use of buprenorphine to modify the signs and symptoms of withdrawal in participants who were primarily opioid dependent. Comparison interventions involved reducing doses of methadone, alpha(2)-adrenergic agonists, symptomatic medications or placebo, or different buprenorphine-based regimes.

Data collection and analysis: One author assessed studies for inclusion and methodological quality, and undertook data extraction. Inclusion decisions and the overall process was confirmed by consultation between all authors.

Main results: Twenty-two studies involving 1736 participants were included. The major comparisons were with methadone (5 studies) and clonidine or lofexidine (12 studies). Five studies compared different rates of buprenorphine dose reduction.Severity of withdrawal is similar for withdrawal managed with buprenorphine and withdrawal managed with methadone, but withdrawal symptoms may resolve more quickly with buprenorphine. It appears that completion of withdrawal treatment may be more likely with buprenorphine relative to methadone (RR 1.18; 95% CI 0.93 to 1.49, P = 0.18) but more studies are required to confirm this.Relative to clonidine or lofexidine, buprenorphine is more effective in ameliorating the symptoms of withdrawal, patients treated with buprenorphine stay in treatment for longer (SMD 0.92, 95% CI 0.57 to 1.27, P < 0.001), and are more likely to complete withdrawal treatment (RR 1.64; 95% CI 1.31 to 2.06, P < 0.001). At the same time there is no significant difference in the incidence of adverse effects, but drop-out due to adverse effects may be more likely with clonidine.

Authors' conclusions: Buprenorphine is more effective than clonidine or lofexidine for the management of opioid withdrawal. Buprenorphine may offer some advantages over methadone, at least in inpatient settings, in terms of quicker resolution of withdrawal symptoms and possibly slightly higher rates of completion of withdrawal.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Acute Disease
  • Buprenorphine / therapeutic use*
  • Clonidine / analogs & derivatives
  • Clonidine / therapeutic use
  • Humans
  • Narcotic Antagonists / therapeutic use*
  • Opioid-Related Disorders / complications
  • Opioid-Related Disorders / drug therapy*
  • Randomized Controlled Trials as Topic
  • Substance Withdrawal Syndrome / drug therapy*


  • Narcotic Antagonists
  • Buprenorphine
  • Clonidine
  • lofexidine