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Alpha2-Adrenergic Agonists for the Reduction or Discontinuation of Opioids or Opioid Substitution Therapy: A Review of Clinical Effectiveness and Guidelines

Last updated: February 23, 2018
Project Number: RC0968-000
Product Line: Rapid Response
Research Type: Drug
Report Type: Summary with Critical Appraisal
Result type: Report


  1. What is the clinical effectiveness of alpha2-adrenergic agonists when used as a tool for the reduction or discontinuation of opioids or opioid substitution therapy?
  2. What are the evidence-based guidelines regarding the use of alpha2-adrenergic agonists for the treatment of patients who are reducing or discontinuing opioids or opioid substitution therapy?

Key Message

Alpha2-adrenergic agonists were found to be more effective than placebo for managing withdrawal, however less effective than buprenorphine and potentially similar to methadone. Hypotension was a common adverse effect with clonidine specifically. Evidence comparing alpha2-adrenergic agonists to non-medicinal support therapies was not identified. Overall the quality of studies was highest in comparisons of alpha2-adrenergic agonists against buprenorphine and placebo, followed by alpha2-adrenergic agonists against methadone, but the evidence was limited in quantity for comparing alpha2-adrenergic agonists to each other. The identified guidelines do not recommend alpha2-adrenergic agonists as a first-line medication when buprenorphine and methadone are an option.