A randomized, double-blind, placebo-controlled study of aripiprazole for the treatment of psychosis in nursing home patients with Alzheimer disease

Objective: To evaluate the efficacy and safety of aripiprazole treatment for psychotic symptoms associated with Alzheimer disease (AD). Methods: In this parallel group, randomized, double-blind, placebo-controlled, flexible-dose trial, institutionalized subjects with AD and psychotic symptoms were randomized to aripiprazole (n = 131) or placebo (n = 125) for 10 weeks. The aripiprazole starting dose was 2 mg/day, and could be titrated to higher doses ( 5, 10, and 15 mg/day) based on efficacy and tolerability. Results: No significant differences in mean change [2 X SD] from baseline between aripiprazole ( mean dose similar to 9 mg/day at endpoint; range = 0.7-15.0 mg) and placebo were detected in the coprimary efficacy endpoints of Neuropsychiatric Inventory-Nursing Home Version (NPI-NH) Psychosis score ( aripiprazole, -4.53 [9.23]; placebo, -4.62 [9.56]; F = 0.02, df = 1, 222, p = 0.883 [ANCOVA]) and Clinical Global Impression (CGI)-Severity score ( aripiprazole, -0.57 [1.63]; placebo, -0.43 [1.65]; F = 1.67, df = 1, 220, p = 0.198 [ANCOVA]) at endpoint. However, improvements in several secondary efficacy measures (NPI-NH Total, Brief Psychiatric Rating Scale Total, CGI - improvement, Cohen-Mansfield Agitation Inventory and Cornell Depression Scale scores) indicated that aripiprazole may confer clinical benefits beyond the primary outcome measures. Treatment-emergent adverse events (AEs) were similar in both groups, except for somnolence ( aripiprazole, 14%; placebo, 4%). Somnolence with aripiprazole was of mild or moderate intensity, and not associated with accidental injury. Incidence of AEs related to extrapyramidal symptoms was low with aripiprazole (5%) and placebo (4%). Conclusions: In nursing home residents with AD and psychosis, aripiprazole did not confer specific benefits for the treatment of psychotic symptoms; but psychological and behavioral symptoms, including agitation, anxiety, and depression, were improved with aripiprazole, with a low risk of AEs.