Cochrane 2014: buprenorphine keeps people in treatment better than placebo; methadone keeps more at flexible doses
31 trials, 5,430 people. Buprenorphine kept people in treatment better than placebo at every dose above 2 mg, and cut illicit opioid use at 16 mg or more. Flexibly dosed, methadone retained more people.
Well-supported by good-quality research. how we score evidence
Caveat on this rating: Flexible-dose methadone retained more people; buprenorphine reduced illicit use only at 16 mg or more. Pre-dates long-acting injectables.
The Cochrane review behind most guidance on buprenorphine maintenance, in both directions.
Significant findings
Mattick, Breen, Kimber and Davoli (Cochrane, 2014) pooled 31 randomised trials with 5,430 participants comparing buprenorphine maintenance with placebo or with methadone. "There is high quality of evidence that buprenorphine was superior to placebo medication in retention of participants in treatment at all doses examined": risk ratios of 1.50 at low doses (2 to 6 mg), 1.74 at medium (7 to 15 mg) and 1.82 at high doses (16 mg or more). On illicit opioid use by urine test, "only high-dose buprenorphine (≥ 16 mg) was more effective than placebo" (SMD -1.17); low and medium doses were not.
Against methadone: "buprenorphine in flexible doses adjusted to participant need, was less effective than methadone in retaining participants" (5 studies, 788 participants, RR 0.83), with no difference in opioid use among those who stayed. At fixed medium or high doses the two "appear no different in effectiveness". The authors' bottom line: "Methadone is superior to buprenorphine in retaining people in treatment, and methadone equally suppresses illicit opioid use."
The other direction
The review found few trials reported adverse events; two that compared them statistically found no difference except more sedation with methadone. Fixed doses are rarely used in practice, the authors note, so the flexible-dose result is the more relevant one. The first author led one included trial and has received untied educational funds from the buprenorphine maker for post-marketing surveillance required by the Australian government; he reports no personal income from it. The review is from 2014, before long-acting injectable buprenorphine.
What this does not show
It does not say one medicine is right for everyone; retention differs by dose and setting. It is not a reason to stop or switch either medicine without the prescriber.
Worth asking
Is my dose high enough to do what the trials found it does, and what would make us change it?
Source
Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence — Mattick RP, Breen C, Kimber J, Davoli M (2014)
Top-tier peer-reviewed journal
Read the source: https://doi.org/10.1002/14651858.CD002207.pub4
DOI: 10.1002/14651858.CD002207.pub4
How this was scored
- Study design
- Meta-analysis of randomised trials
- Funding
- Funding not disclosed
- Published in
- Top-tier peer-reviewed journal
- Sample size
- 5,430
- Preregistered
- not recorded
- Conflicts disclosed
- Yes
- Independent of proponent
- not recorded
- Retracted
- No
Read the full scoring rubric, including what it can't tell you.
Published October 21, 2026.
Questions
How strong is the evidence behind this?
veisund rates this source "strong evidence". Well-supported by good-quality research. It scores 75 out of 100 on our published rubric. One caveat travels with that badge: Flexible-dose methadone retained more people; buprenorphine reduced illicit use only at 16 mg or more. Pre-dates long-acting injectables. The score is calculated from recorded facts about the source — study design, funding, publication venue, sample size, preregistration — not typed in by an editor.
What is the source for this?
Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence — Mattick RP, Breen C, Kimber J, Davoli M (2014). Published in: Top-tier peer-reviewed journal. DOI: 10.1002/14651858.CD002207.pub4. The full source is linked on this page so you can read it yourself.
Who paid for this research, and does that matter?
Study design: Meta-analysis of randomised trials. Funding: Funding not disclosed. Independence from the proponent is not recorded. Industry sponsorship is one of the most reliably measured biases in medicine, which is why funding carries real weight in the score rather than sitting in a footnote.
Is this medical advice?
This is information to bring to your prescriber, not medical advice and not a reason to change anything on your own. Nothing here is an instruction to stop or reduce a medication. If you are in crisis, call or text 988.
This is information to bring to your prescriber, not medical advice and not a reason to change anything on your own. Nothing here is an instruction to stop or reduce a medication. If you are in crisis, call or text 988.