Comparative Risk of Harm Associated with Zopiclone or Trazodone Use in Nursing Home Residents: a Retrospective Cohort Study in Alberta, Canada.

Abstract

There is growing evidence of harm associated with trazodone and nonbenzodiazepine sedative hypnotics (e.g., zopiclone); however, their comparative risk of harm is unknown. We conducted a retrospective cohort study with linked health administrative data, which enrolled older (≥66 years old) nursing home residents living in Alberta, Canada, between December 1, 2009, and December 31, 2018; the last follow-up date was June 30, 2019. We compared the rate of injurious falls and major osteoporotic fractures (primary outcome) and all-cause mortality (secondary outcome) within 180 days of first prescription of zopiclone or trazodone with cause-specific hazard models and inverse probability of treatment weights to control for confounding; primary analysis was intention-to-treat and secondary analysis was per-protocol (i.e., residents censored if dispensed the other exposure drug). Our cohort included 1,403 residents newly dispensed trazodone and 1,599 residents newly dispensed zopiclone. At cohort entry, the mean resident age was 85.7 (standard deviation [SD] 7.4), 61.6% were female, and 81.2% had dementia. New zopiclone use was associated with similar rates of injurious falls and major osteoporotic fractures (intention-to-treat-weighted hazard ratio 1.15, 95% confidence interval [CI] 0.90-1.48; per-protocol-weighted hazard ratio 0.85, 95% CI 0.60-1.21) and all-cause mortality (intention-to-treat-weighted hazard ratio 0.96, 95% CI 0.79-1.16; per-protocol-weighted hazard ratio 0.90, 95% CI 0.66-1.23) compared to trazodone. Zopiclone was associated with a similar rate of injurious falls, major osteoporotic fractures, and all-cause mortality compared to trazodone-suggesting one medication should not be used in lieu of the other. Appropriate prescribing initiatives should also target zopiclone and trazodone.