The Risk Factors and Mortality Among Patients With Different Combination Patterns of Opioids and Benzodiazepines: A Retrospective Study

The concurrent use of opioids and benzodiazepines (BZDs) has raised safety concerns due to increased risks of respiratory depression and death. To evaluate mortality risks linked to different patterns of co-prescription, we conducted a retrospective cohort study using data from a private hospital system between 2008 and 2018. A total of 418 549 opioid users were classified into four groups based on BZD use: opioids only, past use, continuous use, and new initiation. Cox proportional hazards regression model was used to estimate adjusted hazard ratios (aHRs) for 1-year all-cause mortality following 1-year of concomitant use, adjusting for past medical history and Charlson Comorbidity Index (CCI). Compared to the opioids-only group, mortality risks were significantly higher in the continuous (aHR = 1.78), new (aHR = 1.56), and past BZD use groups (aHR = 1.29). Higher mortality was also associated with older age, cancer, and greater comorbidity burden. These findings emphasize the need for cautious prescribing of opioids and BZDs, especially in older adults and those with complex medical conditions.