Are all commonly prescribed antipsychotics associated with increased mortality in reased mortality in elderly male veterans with dementia?

Abstract

Objective: Estimate mortality risk associated with individual commonly-prescribed antipsychotics. Design: 5-year retrospective cohort study. Setting: Veterans national health care data. Participants: Predominantly male, 65 years or older with a diagnosis of dementia and no other known indication for an antipsychotic. Subjects who received an antipsychotic were compared to controls selected randomly from veterans with similar dates of dementia diagnosis and time elapsed from diagnosis to the start of antipsychotic therapy. Exposed and control cohorts were matched by their date of dementia diagnosis and time elapsed from diagnosis to the start of antipsychotic therapy. Measurements: Mortality during incident antipsychotic use. Results: Subjects who were exposed to haloperidol (n=2217), olanzapine (n=3384), quetiapine (n=4277) or risperidone (n=8249) had more co-morbidities than control cohorts. During the first 30 days, there was a significant increase in mortality in subgroups prescribed a daily dose of haloperidol>1mg (hazard ratio (HR) = 3.2, 95% confidence interval (CI): 2.2-4.5, p<0.0001), olanzapine>2.5 mg (HR=1.5, 95%CI: 1.1-2.0, p=0.01) or risperidone>1mg (HR=1.6, 95%CI: 1.1-2.2, p=0.01) adjusted for demographic, co-morbidity and medication history using Cox regression analyses. Increased mortality was not seen when quetiapine >50 mg (HR=1.2, 95%CI: 0.7-1.8, p=0.5) was prescribed, and there was no increased mortality associated with a dose iii <50 mg (HR=0.7, 95%CI 0.5 to 1.0, p=0.03). No antipsychotic was associated with increased mortality after the first 30 days. Conclusions: Commonly prescribed doses of haloperidol, olanzapine and risperidone, but not quetiapine, were associated with a short-term increase in mortality. Further investigations are warranted to determine causality and identify patient characteristics and antipsychotic dosage regimens that are not associated with an increased risk of mortality in elderly patients with dementia.