AIMS: To estimate whether opioid substitution treatment (OST) with buprenorphine or methadone is associated with a greater reduction in the risk of all-cause mortality (ACM) and opioid drug-related poisoning (DRP) mortality.

DESIGN: Cohort study with linkage between clinical records from Clinical Practice Research Datalink and mortality register.

PARTICIPANTS: A total of 11 033 opioid-dependent patients in the UK who received OST from 1998 to 2014, followed-up for 30 410 person-years.

MEASUREMENTS: Exposure to methadone (17 373, 61%) OST episodes or buprenorphine (9173, 39%) OST episodes. ACM was available for all patients; information on cause of death and DRP was available for 5935 patients (54%) followed-up for 16 363 person-years. Poisson regression modelled mortality by treatment period with an interaction between OST type and treatment period (first 4 weeks on OST, rest of time off OST, first 4 weeks off OST, rest of time out of OST censored at 12 months) to test whether ACM or DRP differed between methadone and buprenorphine. Inverse probability weights were included to adjust for confounding and balance characteristics of patients prescribed methadone or buprenorphine.

FINDINGS: ACM and DRP rates were 1.93 and 0.53 per 100 person-years, respectively. DRP was elevated during the first 4 weeks of OST [incidence rate ratio (IRR) = 1.93 95% confidence interval (CI) = 0.97-3.82], the first 4 weeks off OST (IRR = 8.15, 95% CI = 5.45-12.19) and the rest of time out of OST (IRR = 2.13, 95% CI = 1.47-3.09) compared with mortality risk from 4 weeks to end of treatment. Patients on buprenorphine compared with methadone had lower ACM rates in each treatment period. After adjustment, there was evidence of a lower DRP risk for patients on buprenorphine compared with methadone at treatment initiation (IRR = 0.08, 95% CI = 0.01-0.48) and rest of time on treatment (IRR = 0.37, 95% CI = 0.17-0.79). Treatment duration (mean and median) was shorter on buprenorphine than methadone (173 and 40 versus 363 and 111, respectively). Model estimates suggest that there was a low probability that methadone or buprenorphine reduced the number of DRP in the population: 28 and 21%, respectively.

CONCLUSIONS: In UK general medical practice, opioid substitution treatment with buprenorphine is associated with a lower risk of all-cause and drug-related poisoning mortality than methadone. In the population, buprenorphine is unlikely to give greater overall protection because of the relatively shorter duration of treatment.