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 × SD] from baseline between aripiprazole (mean dose ∼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.