Scientific article
Published by / Citation
Degenhardt, L., Clark, B., Macpherson, G., Leppan, O., Nielsen, S., Zahra, E., ... & Farrell, M. (2023). Buprenorphine versus methadone for the treatment of opioid dependence: a systematic review and meta-analysis of randomised and observational studies. The Lancet Psychiatry.

Buprenorphine versus methadone for the treatment of opioid dependence



Opioid dependence is associated with substantial health and social burdens, and opioid agonist treatment (OAT) is highly effective in improving multiple outcomes for people who receive this treatment. Methadone and buprenorphine are common medications provided as OAT. We aimed to examine buprenorphine compared with methadone in the treatment of opioid dependence across a wide range of primary and secondary outcomes.


The authors conducted a systematic review and meta-analysis of studies comparing treatment with buprenorphine or methadone. Primary outcomes were retention in treatment at 1, 3, 6, 12, and 24 months, treatment adherence (measured through doses taken as prescribed, dosing visits attended, and biological measures), or extra-medical opioid use (measured by urinalysis and self-report). Secondary outcomes were the use of benzodiazepines, cannabis, cocaine, amphetamines, and alcohol; withdrawal; craving; criminal activity and engagement with the criminal justice system; overdose; mental and physical health; sleep; pain; global functioning; suicidality and self-harm; and adverse events. S


The researches identified 32 eligible randomised control trials and 69 observational studies comparing buprenorphine and methadone, in addition to 51 randomised control trials and 124 observational studies that reported on treatment retention with buprenorphine.

Overall, 61 studies were done in western Europe, 162 in North America, 14 in north Africa and the Middle East, 20 in Australasia, five in southeast Asia, seven in south Asia, two in eastern Europe, three in central Europe, one in east Asia, and one in central Asia.

  • At timepoints beyond 1 month, retention was better for methadone than for buprenorphine
  • Retention was generally higher in randomised control trials than observational studies.
  • There was no evidence suggesting that adherence to treatment differed with buprenorphine compared with methadone.
  • There was some evidence that extra-medical opioid use was lower in those receiving buprenorphine in RCTs that measured this outcome by urinalysis, but no differences were found when using other measures.
  • There was evidence of reduced cocaine use, cravings, anxiety, and cardiac dysfunction, as well as increased treatment satisfaction among people receiving buprenorphine compared with methadone
  • There was evidence of reduced hospitalisation and alcohol use in people receiving methadone. 


Evidence from trials and observational studies suggests that treatment retention is better for methadone than for buprenorphine. Comparative evidence on other outcomes examined showed few statistically significant differences and was generally based on small numbers of studies. These findings highlight the imperative for interventions to improve retention, consideration of client-centred factors (such as client preference) when selecting between methadone and buprenorphine, and improved data collection and reporting to strengthen future research.

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