Risk of drug-related death associated with co-prescribing of gabapentinoids and Z-drugs among people receiving opioid-agonist treatment: A national retrospective cohort study.

Background: Prescribing of gabapentinoids and Z-drug-hypnotics has increased in the population and among people receiving opioid-agonist treatment (OAT) for opioid dependence. Evidence is mixed on whether co-prescribing of sedatives such as gabapentinoids and Z-drugs during OAT increases risk of drug-related death (DRD).

Methods: We conducted a retrospective cohort study of individuals prescribed OAT between 2011 and 2020 in Scotland. Prescribing records were linked to mortality data and other healthcare datasets (sociodemographic, comorbidity). We identified episodes of treatment with gabapentinoids/Z-drugs and used multivariable quasi-Poisson regression to model associations between co-prescription and DRD risk.

Results: Among 46,602 individuals with 304,783 person-years of follow-up, we found that co-prescription was common, with 25 % and 34 % ever being co-prescribed gabapentinoids and Z-drugs, respectively. Gabapentinoid exposure was strongly associated (adjusted hazard ratio (aHR)=2·18, 95 % CI=1·92, 2·46) and Z-drug exposure moderately associated (aHR=1·39, 95 % CI=1·15, 1·66) with elevated risk of DRD. Gabapentinoid exposure was associated with DRD risk on and off OAT; Z-drug exposure was less strongly associated with DRD risk when on OAT.

Conclusions: Co-prescription of gabapentinoids and Z-drugs is common among OAT patients. However, co-prescription is associated with increased risk of DRD. Alternatives to prescribing sedative medications to OAT patients and/or greater monitoring - if prescribed - are needed.