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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.

Objective To assess the efficacy and safety of aripiprazole for psychosis associated with Alzheimer dementia (AD). Methods In this double-blind, multicenter study, 487 institutionalized patients with psychosis associated with AD were randomized to placebo or aripiprazole, 2, 5 or 10 mg/day. Primary efficacy assessment was the mean change from baseline to week 10 on the Neuropsychiatric Inventory–Nursing Home (NPI-NH) version Psychosis Subscale score. Secondary measures included NPI-NH Total, Clinical Global Impression–Severity of Illness (CGI-S), Brief Psychiatric Rating Scale (BPRS) Core and Total, and the Cohen–Mansfield Agitation Inventory (CMAI) scores. Results Aripiprazole 10 mg/day showed significantly greater improvements (mean change [2 × SD]) than placebo on the NPI-NH Psychosis Subscale (−6.87 [8.6] versus −5.13 [10.0]; F=6.29, df=1, 422, p=0.013 by analysis of covariance [ANCOVA]); CGI-S (−0.72 [1.8] versus −0.46 [1.6]; F=4.68, df=1, 419, p=0.031 [ANCOVA]); BPRS Total (−7.12 [18.4] versus −4.17 [21.6]; F=4.72, df=1, 399, p=0.030 [ANCOVA]); BPRS Core (−3.07 [6.9] versus −1.74 [7.8]; F=7.30, df=1, 407, p=0.007 [ANCOVA]); CMAI (−10.96 [22.6] versus −6.64 [28.6]; F=5.23, df=1, 410, p=0.023 [ANCOVA]), and NPI-NH Psychosis response rate (65 versus 50%; χ 2 = 5.52, df=1, p=0.019 [CMH]). Aripiprazole 5 mg/day showed significant improvements versus placebo on BPRS and CMAI scores. Aripiprazole 2 mg/day was not efficacious. Cerebrovascular adverse events were reported: aripiprazole 2 mg/day, N=1; 5 mg/day, N=2; 10 mg/day, N=4; placebo, N=0. No deaths in any group (aripiprazole 2 mg/day, 3%; 5 mg/day, 2%; 10 mg/day, 7%; placebo, 3%) were considered to be treatment-related. Conclusion Aripiprazole 10 mg/day was efficacious and safe for psychosis associated with AD, significantly improving psychotic symptoms, agitation, and clinical global impression. However, clinicians should be aware of the safety considerations of atypical antipsychotic uses in this population.