We observed an increased risk of mortality associated with benzodiazepine-opioid coprescriptions among younger but not older participants (adjusted HR, 3.27 [95% CI, 2.40-4.47] vs 1.21 [95% CI, 0.86-1.70]), with similar findings among those receiving benzodiazepines without opioids (adjusted HR, 1.81 [95% CI, 1.29-2.54] vs 0.84 [95% CI, 0.67-1.05]) (Table 2). Among those older than 65 years in age-stratified analyses, we consistently observed no increased risk of death associated with cotreatment across all adjusted comparisons. Analyses were also repeated across participants of different follow-up periods, using the 50th percentile as a threshold between short-term and long-term follow-up strata. Among those receiving benzodiazepines without opioids, weighted analyses showed an increased risk of death in those with longer (≥50th percentile) but not shorter follow-up times (HR, 2.17 [95% CI, 1.59-2.98] vs 1.17 [95% CI, 0.92-1.50]). Weighted analyses showed similarly elevated hazards of death among those receiving benzodiazepine and opioid cotreatment regardless of follow-up time (<50th percentile: HR, 1.35 [95% CI, 1.04-1.76] vs ≥50th percentile: HR, 1.93 [95% CI, 1.29-2.88]).
