Comparative risk of harm associated with trazodone or atypical antipsychotic use in older adults with dementia: a retrospective cohort study

BACKGROUND: Trazodone is increasingly prescribed for behavioural and psychological symptoms of dementia, but little is known about its risk of harm. Our objective was to describe the comparative risk of falls and fractures among older adults with dementia dispensed trazodone or atypical antipsychotics. METHODS: The study cohort included adults with dementia (excluding patients with chronic psychotic illnesses) living in long-term care and aged 66 years and older. Data were obtained from routinely collected, linked health administrative databases in Ontario, Canada. We compared new users of trazodone with new users of atypical antipsychotics (quetiapine, olanzapine or risperidone) between Dec. 1, 2009, and Dec. 31, 2015. The primary outcome was a composite of fall or major osteoporotic fracture within 90 days of first prescription. Secondary outcomes were falls, major osteoporotic fractures, hip fractures and all-cause mortality. RESULTS: We included 6588 older adults dispensed trazodone and 2875 dispensed an atypical antipsychotic, of whom 95.2% received a low dose of these medications. Compared with use of atypical antipsychotics, use of trazodone was associated with similar rates of falls or major osteoporotic fractures (weighted hazard ratio [HR] 0.89, 95% confidence interval [CI] 0.73 to 1.07), major osteoporotic fracture (weighted HR 1.03, 95% CI 0.73 to 1.47), falls (weighted HR 0.91, 95% CI 0.75 to 1.11) and hip fractures (weighted HR 0.92, 95% CI 0.59 to 1.43). Use of trazodone was associated with a lower rate of mortality (weighted HR 0.75, 95% CI 0.66 to 0.85). INTERPRETATION: Trazodone is not a uniformly safer alternative to atypical antipsychotics, given the similar risk of falls and fractures among older adults with dementia.