A review of treatment-emergent adverse events during olanzapine clinical trials in elderly patients with dementia.

OBJECTIVE: Olanzapine and other antipsychotics are not approved by the U.S. Food and Drug Administration to treat behavioral disturbances associated with dementia, but they are often prescribed to these patients. Although antipsychotics may be efficacious in this population, elderly patients with dementia may be particularly vulnerable to adverse events. This article reviews the safety of olanzapine in elderly patients with dementia. DATA SOURCES: Data from 6 studies comparing olanzapine to placebo, risperidone, or conventional antipsychotics in elderly patients with dementia were analyzed for mortality, cerebrovascular adverse events (CVAEs), and other adverse events. These trials represent all Lilly olanzapine-comparator trials in this population. The data included integration of 5 double-blind, placebo-controlled studies (olanzapine, N = 1184; placebo, N = 478; median age = 79 years; 1 study also compared olanzapine with risperidone, N = 196) and an open-label study comparing olanzapine (N = 150) with conventional antipsychotics (N = 143). DATA SYNTHESIS: Incidence of mortality was significantly higher in olanzapine- (3.5%) than in placebo-treated patients (1.5%; p = .024). There were no significant differences in the crude incidence of mortality between olanzapine- (2.9%) and risperidone- (2.0%) or olanzapine- (14.8%) and conventional antipsychotic-treated patients (16.1%; p = .871). Risk factors associated with mortality in olanzapine-treated patients included age >/= 80, concurrent benzodiazepine use, treatment-emergent sedation, or treatment-emergent pulmonary conditions. Incidence of CVAEs was approximately 3 times higher in olanzapine- (1.3%) than in placebo-treated patients (0.4%). There were no significant differences in the incidence of CVAEs between olanzapine- (2.5%) and risperidone- (2.0%; p = 1.0) or olanzapine- (3.4%) and conventional antipsychotic-treated patients (4.3%; p = .765). CONCLUSION: These findings should be considered if prescribers elect to treat behavioral disturbances associated with dementia in the elderly with olanzapine or other antipsychotics.