Objective: Mortality from opioid use disorder (OUD) can be reduced for patients who receive opioid agonist treatment (OAT). In the United States (US), OATs have different requirements including nearly daily visits to a dispensing facility for methadone but weekly to monthly prescriptions for buprenorphine. Our objective was to compare mortality rates for buprenorphine and methadone treatments among a large sample of US patients with OUD.
Methods: We measured all-cause mortality, overdose mortality, and suicide mortality among US Department of Veterans Affairs patients with a diagnosis of OUD who received OAT from 2010 through 2019. We leveraged substantial and sustained regional variation in prescribing buprenorphine versus methadone as an instrumental variable (IV) and used inverse propensity of treatment weighting to balance relevant covariates across treatment groups. We compared mortality with true two-stage IV using both probit and linear probability models, as well as a reduced form IV model, adjusting for demographics and health status.
Results: Our cohort consisted of 61,997 patients with OUD who received OAT, of whom 92.7% were male with a mean age of 47.9 (SD = 14.1) years. Patients were followed for a median of 2 (IQR = 1,4) calendar years. Across regional terciles, mean methadone prescribing was 4.8%, 19.5%, and 75.1% of OAT patients. All models identified significant reductions in all-cause and suicide mortality for buprenorphine relative to methadone. For example, predicted all-cause mortality from the probit model was 169.7 per 10,000 person years (95% CI, 157.8, 179.6) in the lowest tercile of methadone prescribing compared with 206.1 (95% CI, 196.0, 216.3) in the highest tercile. No difference was identified for overdose mortality.
Conclusion: We found significantly lower all-cause mortality and suicide mortality rates for buprenorphine compared with methadone. Our results support the less restrictive prescribing practices for buprenorphine as OAT in the US.
Keywords: instrumental variable analysis; mortality; opioid agonist treatment; opioid use disorder; veterans.
Published 2022. This article is a U.S. Government work and is in the public domain in the USA.