Dose trajectories associated with non-fatal overdose among patients co-prescribed opioids and benzodiazepines:...

To assess opioid and benzodiazepine prescribing trajectories associated with overdose.

Retrospective cohort study of Optum Labs Data Warehouse data which includes de-identified medical and pharmacy claims and enrollment records for commercial and Medicare Advantage enrollees. The database contains longitudinal health information on patients, representing a mixture of ages and geographical regions across the United States. The cohort comprised adults prescribed opioids for 80 % of a 180-day baseline period ending with at least 10 days of overlapping opioid and benzodiazepine coverage from July 1, 2016 to December 31, 2021 (N = 182,477). The primary outcome was an opioid or benzodiazepine overdose resulting in emergency or hospital services through December 31, 2022. Time-varying covariates included: 1) short-term trajectory based on recent change in mean daily morphine milligram equivalents (MME) or diazepam milligram equivalents (DME); and 2) long-term trajectory based on 180-day trend.

For both opioids and benzodiazepines, overdose risk was increased with both decreasing and increasing short-term and long-term trajectories relative to stable doses. Compared to stable dosing, short-term decreases in MME and DME were associated with similar magnitudes of increased overdose risk [adjusted hazard ratios (aHRs) 1.41 (95 % CI: 1.31-1.52) vs. 1.23 (95 % CI: 1.12-1.35), respectively), as were long-term decreases in MME and DME [aHRs 1.29 (95 % CI: 1.21-1.38) vs. 1.36 (95 % CI: 1.24-1.48), respectively).

Among co-prescribed patients, decreasing short- and long-term trajectories of either opioids or benzodiazepines were associated with a similar increase in non-fatal overdose risk.