Trazodone: Not Safer Than Atypical Antipsychotics in Patients With Dementia

The use of trazodone in older patients with dementia was associated with similar levels of risk for falls and fractures as atypical antipsychotics and thus cannot be considered a uniformly safer alternative to those agents, according to a retrospective analysis published in the Canadian Medical Association Journal.

Approximately 48% of patients with dementia exhibit aggressive behavior. This is often treated with atypical antipsychotics or trazodone. Antipsychotic use in patients with dementia is high in Canada — where it approaches 34% in adults living with dementia in long-term care facilities — and is also prevalent in Europe and the United States. Still, these medications are often associated with substantial harm to older patients, including myocardial infarction, aspiration pneumonia, and death, as well as fractures as the result of falls. In randomized clinical trials, adverse effects associated with the use of trazodone in patients with dementia included parkinsonism, drowsiness, dizziness, and hypotension, any of which could increase the risk for falls and fracture.

Using data from healthcare databases in Ontario, Canada, Jennifer A. Watt, MD, of the division of geriatric medicine, University of Toronto in Canada, and colleagues evaluated the comparative risks of the primary composite end point of falls and major osteoporotic fractures in older adults with dementia who received treatment with either trazodone or atypical antipsychotics between December 1, 2009 and December 31, 2015.

The investigators identified 6588 older adults who were treated with trazodone and 2875 treated with an atypical antipsychotic. Trazodone therapy resulted in a similar rate of falls or major osteoporotic fractures as therapy with an atypical antipsychotic (weighted hazard ratio [HR] 0.89), major osteoporotic fracture (weighted HR 1.03), falls (weighted HR 0.91), and hip fractures (weighted HR 0.92); however, trazodone was associated with a lower mortality rate (weighted HR 0.75).

The study was limited by its nonrandomized retrospective nature and use of healthcare databases. The use of a moderately to severely frail population of patients with dementia may limit the generalizability of these findings. Furthermore, the investigators noted that as data on falls and fractures were limited to patients presenting to a hospital, the actual incidence of falls and fractures may be underestimated.

The researchers cautioned against consideration of trazodone as a safe alternative to atypical antipsychotics. They further advised that as clinicians rightly move to decrease the use of antipsychotics in patients with dementia, collateral changes in clinical practice must be considered.

Reference

Watt JA, Gomes T, Bronskill SE, et al. Comparative risk of harm associated with trazodone or atypical antipsychotic use in older adults with dementia: a retrospective cohort study. CMAJ. 2018;190:E1376-E1383.