OBJECTIVES: The main objectives were: (1) characterize patients in the UK who received a prescription for buprenorphine/naloxone (BUP/NLX), buprenorphine alone, or methadone; and (2) assess all-cause mortality rates in these medication groups.

METHODS: In this retrospective observational study, electronic records from The Health Improvement Network (THIN) database were searched for BUP/NLX (sublingual tablet), buprenorphine (sublingual tablet), and methadone prescriptions issued between 1-Jan-2007 and 31-Dec-2015. Mortality rates were analyzed in the overall population (BUP/NLX=964; buprenorphine=1865; methadone=6363). Two designs were used for comparative analyses: (1) new-user cohort, defined as patients (case subjects) with ≥1 year enrollment before first prescription (BUP/NLX=615; buprenorphine=1011; methadone=2723); and (2) case-control design, nested within the new-user cohort with ≤5 matched-controls randomly sampled for each case subject. Cox regression was used to analyze hazard ratios (HRs) for mortality in the new-user cohort; logistic regression was used to analyze odds ratios (ORs) for exposure to study drug (defined as “current”, “recent”, or “past or never”) in the nested case-control cohort. Analyses were adjusted for baseline covariates, and all P-values were two-sided.

RESULTS: Most of the 964 BUP/NLX users were male (70.5%) and aged 20-49 years (94.2%). Mortality rates per 1000 person-year (95% CI) were: BUP/NLX, 5.29 (3.02-8.58); buprenorphine, 10.79 (8.50-13.50); methadone, 28.34 (26.18-30.63). In the new-user cohort, HRs for all-cause mortality for buprenorphine and methadone relative to BUP/NLX were 1.05 (P=0.90) and 4.47 (P<0.001), respectively. ORs for “current” and “recent” BUP/NLX exposure relative to “past or never” exposure were 0.47 (P=0.06) and 1.57 (P=0.36), respectively.

LIMITATIONS: This was a retrospective analysis of an EMR database, with no randomization to treatment. Results may be confounded by unknown/unmeasured factors such as comorbid mental disorders and/or substance-related disorders.

CONCLUSIONS: All-cause mortality rates were lowest among BUP/NLX users and highest among methadone users. Methadone was associated with 3-5 fold increased risk of all-cause mortality.