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Buprenorphine/Naloxone Versus Methadone for the Treatment of Opioid Dependence: A Review of Comparative Clinical Effectiveness, Cost-Effectiveness and Guidelines

Last updated: September 2, 2016
Project Number: RD0032-000
Product Line: Rapid Response
Research Type: Drug
Report Type: Peer-reviewed summary with critical appraisal
Result type: Report


  1. What is the clinical effectiveness of buprenorphine/naloxone compared with methadone for the treatment of patients with opioid dependence?
  2. What is the cost-effectiveness of buprenorphine/naloxone compared with methadone for the treatment of patients with opioid dependence?
  3. What are the evidence-based guidelines associated with the use of buprenorphine/naloxone for the treatment of patients with opioid dependence?

Key Message

​The comparative clinical effectiveness of maintenance treatment with buprenorphine/naloxone and methadone for the treatment of opioid use disorder was assessed in five randomized controlled trials and five non-randomized studies.

It was shown that more methadone patients were retained in treatment compared with buprenorphine/naloxone. Patients who stopped treatment did so for a variety of reasons including loss to follow-up and non-compliance with medication. Patients on buprenorphine/naloxone were more likely than patients on methadone to abstain from opioid use when measured quantitatively through urine testing. Of note, patients may have been under-dosed in the studies and hence, the true effectiveness of buprenorphine/naloxone and methadone may actually be greater than what was reported in the studies. Specifically, in one study buprenorphine/naloxone showed a linear dose-response relationship. Higher doses of methadone and of buprenorphine/naloxone were more effective than lower doses.

There was no statistically significant difference between buprenorphine/naloxone and methadone in the number of patients experiencing harms, including mortality.

The results of four economic evaluations showed that treatment with buprenorphine/naloxone was more effective but more costly than treatment with methadone; however the incremental cost effectiveness ratios were small. In some scenarios, buprenorphine/naloxone was dominant (more effective and less costly).  Applicability of these results to the Canadian setting is unclear.

One Canadian clinical practice guideline specific to buprenorphine/naloxone and dated 2011 recommends that the choice of treatment be guided by the individual clinical circumstances and patient preference.

Overall, buprenorphine/naloxone appears to be a safe, effective, and cost-effective choice for treating opioid use disorder compared with methadone.