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.
The prevalence of dementia in Canada is 7.1%, but the rate approaches 25% among Canadians aged 85 years and older. Importantly, 61.9% of residents in continuing care facilities have dementia, and 48% have demonstrated aggressive behaviours. The behavioural and psychological symptoms of dementia (e.g., aggression) can lead to caregiver burden and difficulty in providing safe and timely care for patients with dementia. Despite the limited evidence of treatment efficacy, both antipsychotics and trazodone (an antidepressant medication) are commonly used to alleviate the behavioural and psychological symptoms of dementia. In 2013, 34% of older adults with dementia living in a long-term care facility in Ontario, Canada, were dispensed an atypical antipsychotic, and 21.3% were dispensed trazodone. Similarly high rates of antidepressant and atypical antipsychotic use were reported among patients with dementia in the United States and Europe.
Antipsychotics are associated with substantial harm among older adults with dementia, including myocardial infarction, aspiration pneumonia and death. There is growing concern about the use of antipsychotics for indications other than the treatment of chronic psychotic illnesses. Clinical practice guidelines and quality-improvement initiatives have encouraged clinicians to decrease antipsychotic use in older adults with dementia. Comparatively, little is known about the risk of harm from trazodone in older adults with dementia — despite its increasing use. In Ontario, the prevalence of trazodone prescriptions has risen sharply, from 7.7% in 2002 to 21.3% in 2013.3 Randomized controlled trials (RCTs) of trazodone in patients with dementia described adverse effects, including parkinsonism, drowsiness, dizziness and hypotension, which could contribute to an increased risk of falls or fractures; only one study reported a patient was lost to follow-up in its placebo arm for having a fracture. Understanding how potential harms associated with trazodone compare with the harms associated with antipsychotics is important because we know there are risks associated with antipsychotic use in older adults. Clinicians might use trazodone to treat the behavioural and psychological symptoms of dementia instead of antipsychotics to avoid these risks.
We examined the comparative risk of the composite outcome of falls and major osteoporotic fractures, falls, major osteoporotic fractures, hip fractures and all-cause mortality among older adults with dementia dispensed trazodone or atypical antipsychotics.
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