Objective
The use of antipsychotics to treat the behavioral symptoms of dementia is associated with increased mortality. However, there remains limited information regarding individual agents’ risks.
Method
This was a retrospective cohort study using national data from the US Department of Veterans Affairs (fiscal years 1999–2008) for patients ≥65 years old with dementia, beginning outpatient treatment with an antipsychotic (risperidone, olanzapine, quetiapine, and haloperidol) or valproic acid and its derivatives (as a non-antipsychotic comparison). The total sample included 33,604 patients. Individual drug groups were compared for 180-day mortality rates. Potential confounding was addressed using multivariate models and propensity adjustments.
Results
In covariate-adjusted intent to treat analyses, haloperidol users had the highest mortality rates (relative risk 1.54, 95% confidence interval 1.38–1.73) followed by risperidone (reference), olanzapine (RR 0.99, 95% CI 0.89–1.10), valproic acid and its derivatives (RR 0.91, 95% CI 0.78–1.06) and quetiapine (RR 0.73, 95% CI 0.67–0.80). Propensity-stratified and propensity-weighted models as well as analyses controlling for site of care and medication dosage showed similar patterns. Haloperidol risk was highest in the first 30 days and then significantly and sharply decreased. Among the other agents, mortality risk differences were most significant in the first 120 days and declined in the subsequent 60 days during 180-day follow-up.
Conclusions
There may be differences in mortality risks among individual antipsychotic agents. Further, the use of valproic acid and its derivatives as alternative agents to address the neuropsychiatric symptoms of dementia may carry associated risks as well.
Use of atypical antipsychotics began to decline significantly in 2003, and the Food and Drug Administration advisory was temporally associated with a significant acceleration in the decline.
Antipsychotic medications taken by patients with dementia were associated with higher mortality rates than were most other medications used for neuropsychiatric symptoms. The association between mortality and antipsychotics is not well understood and may be due to a direct medication effect or the pathophysiology underlying neuropsychiatric symptoms that prompt antipsychotic use.
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