Benzodiazepine, z-drug and pregabalin prescriptions and mortality among patients in opioid maintenance treatment-A nation-wide register-based open cohort study

- Prescriptions of sedatives were common in subjects with opioid dependence.
- Prescriptions of pregabalin and z-drugs were associated with overdose mortality.
- Benzodiazepine prescription approached significant association with overdose death.
- Benzodiazepines were strongly associated with all-cause and non-overdose deaths.
- Physicians should be cautious about sedative prescription in opioid dependence.

BackgroundUse of sedatives may increase risk of death in opioid users. The aim of the study was to assess whether prescription of sedatives may be associated with mortality in patients in opioid maintenance treatment.MethodsThis retrospective register-based open cohort study included nation-wide register data including all individuals who were dispensed methadone or buprenorphine as opioid maintenance treatment for opioid dependence between July, 2005 and December, 2012 (N = 4501). Outcome variables were overdose mortality and non-overdose mortality, respectively. Extended Cox regression analyses examined associations between type of sedative prescriptions and death, controlling for sex, age, previous overdoses and suicide attempts, psychiatric in-patient treatment and opioid maintenance treatment status. Opioid maintenance was assumed to last for 90 days (or 30 days in a sensitivity analysis) after the last methadone or buprenorphine prescription.ResultsBenzodiazepine prescriptions were associated with non-overdose death (HR: 2.02, 95% CI: 1.29-3.18) but not significantly associated with overdose death (1.49, 0.97-2.29). Z-drug (1.60, 1.07-2.39) and pregabalin prescriptions (2.82, 1.79-4.43) were associated with overdose death. In the sensitivity analysis, all categories of sedatives, including benzodiazepines, were significantly associated with overdose death.ConclusionsCaution is advised when prescribing sedative drugs, including benzodiazepines, z-drugs and pregabalin, to patients in opioid maintenance treatment.