Alpha2-adrenergic agonists in opioid withdrawal

Addiction. 2002 Jan;97(1):49-58. doi: 10.1046/j.1360-0443.2002.00037.x.


Objectives: This paper presents the main findings of a systematic (Cochrane) review of the effectiveness of alpha2-adrenergic agonists in managing opioid withdrawal.

Design: The original systematic review included controlled trials that compared alpha2-adrenergic agonists with another form of treatment (or placebo) in participants who were primarily opioid-dependent.

Main findings: Ten studies compared a treatment regime based on an alpha2-adrenergic agonist with one based on reducing doses of methadone. Withdrawal intensity is similar to, or marginally greater with alpha2-adrenergic agonists, but signs and symptoms of withdrawal occur and resolve earlier in treatment. Participants stay in treatment longer with methadone. The likelihood of completing withdrawal is similar, or slightly less, with clonidine or lofexidine. Clonidine is associated with more adverse effects than reducing doses of methadone. Three studies compared the alpha2-adrenergic agonists, clonidine and lofexidine. Lofexidine does not reduce blood pressure to the same extent as clonidine, but is otherwise similar to clonidine.

Conclusions: Participants stay in treatment longer with methadone regimes, which may provide greater opportunity for psychosocial intervention. Methadone regimes may be preferable for withdrawal in outpatient settings where the risk of relapse to heroin use is high. The use of methadone may also facilitate transfer to maintenance treatment should completion of withdrawal become unlikely. For those who are well prepared for withdrawal and seeking earlier resolution of withdrawal symptoms, alpha2-adrenergic agonist treatment may be preferred. Clonidine and lofexidine appear equally effective for inpatient settings, but the lower incidence of hypotension makes lofexidine more suited to use in outpatient settings.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Adrenergic alpha-Agonists / therapeutic use*
  • Clonidine / analogs & derivatives*
  • Clonidine / therapeutic use
  • Confidence Intervals
  • Controlled Clinical Trials as Topic
  • Humans
  • Methadone / therapeutic use
  • Narcotics / therapeutic use
  • Odds Ratio
  • Opioid-Related Disorders / drug therapy*
  • Substance Withdrawal Syndrome / drug therapy*
  • Treatment Outcome


  • Adrenergic alpha-Agonists
  • Narcotics
  • Clonidine
  • Methadone
  • lofexidine