"Long-term retention on OAT in trials and observational studies is suboptimal, which limits the effect of OAT with regard to reducing drug-related deaths.131 There was consistent evidence that retention was slightly better on methadone than buprenorphine across RCTs and observational studies at timepoints beyond 1 month, although few RCTs examined long-term retention.

"The amount and reporting of other outcome data for comparisons between buprenorphine and methadone were inconsistent. There was inconsistent evidence that extra-medical opioid use and use of cocaine might be lower among people prescribed buprenorphine. Limited evidence (typically from single studies) suggested that some other outcomes might differ between buprenorphine and methadone, more commonly favouring buprenorphine, but overall there remains considerable scope for expanding evidence for many outcomes.

"Previous reviews have shown good evidence that, compared with methadone, sublingual buprenorphine has a lower risk of death due to overdose during the first month of treatment, but not after that time,11 which might be linked to differences in effects on respiratory depression.9 Despite that risk, given the poorer retention in treatment and the absence of clear evidence of strong benefits in other areas, it is not clear that buprenorphine should yet be recommended as a first-line treatment.

"Only one observational study54 has directly compared methadone with extended-release buprenorphine, and few studies have been published on retention in treatment with this new formulation of buprenorphine. Despite small study numbers and an absence of well powered RCTs, there are indications that retention might be higher with extended-release than sublingual buprenorphine, suggesting that the changed formulation might partly address issues related to retention; however, large-scale RCTs and real-world data showing outcomes from large-scale implementation are needed.

"Many outcomes showed no statistically significant difference between medications. Given that few differences were found between methadone and buprenorphine, other factors such as patient preference,132 access to unsupervised dosing, and cost133 to the individual are important factors to consider. Studies should also examine the effect of an individual's medication preference on treatment outcomes, particularly retention."


Louisa Degenhardt, Brodie Clark, Georgina Macpherson, Oscar Leppan, Suzanne Nielsen, Emma Zahra, Briony Larance, Jo Kimber, Daniel Martino-Burke, Matthew Hickman, Michael Farrell. Buprenorphine versus methadone for the treatment of opioid dependence: a systematic review and meta-analysis of randomised and observational studies. The Lancet Psychiatry, 2023. ISSN 2215-0366. doi.org/10.1016/S2215-0366(23)00095-0.