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


Project Status:
Project Line:
Health Technology Review
Project Sub Line:
Summary with Critical Appraisal
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  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.