Christopher Breder

Aripiprazole for the treatment of psychosis in patients with Alzheimer's disease: a randomized, placebo-controlled study.

Abstract: This study compared the efficacy, safety, and tolerability of aripiprazole, a novel antipsychotic, with placebo in patients with psychosis associated with Alzheimers Disease (AD). This 10-week, double-blind, multicenter study randomized 208 outpatients (mean age, 81.5 years) with AD-associated psychosis to aripiprazole (n = 106) or placebo (n = 102). The initial aripiprazole dose of 2 mg/d was titrated upwards (5, 10, or 15 mg/d) according to efficacy and tolerability. Evaluations included Neuropsychiatric Inventory (NPI) Psychosis subscale and Brief Psychiatric Rating Scale (BPRS), adverse event (AE) reports, extrapyramidal symptoms (EPS) rating scales, and body weight. Overall, 172 patients (83%) completed the study. Mean aripiprazole dose at end point was 10.0 mg/d. The NPI Psychosis subscale score showed improvements in both groups (aripiprazole, −6.55; placebo, −5.52; P = 0.17 at end point). Aripiprazole-treated patients showed significantly greater improvements from baseline in BPRS Psychosis and BPRS Core subscale scores at end point compared with placebo. AEs were generally mild to moderate in severity and included (aripiprazole vs. placebo): urinary tract infection (8% vs. 12%), accidental injury (8% vs. 5%), somnolence (8% vs. 1%), and bronchitis (6% vs. 3%). Somnolence was mild and not associated with falls or accidental injury. There were no significant differences from placebo in EPS scores, or clinically significant ECG abnormalities, vital signs, or weight. In conclusion, aripiprazole showed similar improvements to placebo in psychotic symptoms as assessed by NPI Psychosis subscale scores, but significantly greater effects on BPRS Core and Psychosis assessments in community-living AD patients with psychosis. Aripiprazole was safe and well tolerated in this patient population.

A randomized, multicenter, double-blind, placebo-controlled study of the efficacy and safety of aripiprazole for the treatment of alcohol dependence.

The purpose of this study was to compare the efficacy and safety of aripiprazole with placebo in the treatment of alcoholics. In this 12-week multicenter, double-blind study, 295 patients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition alcohol dependence were randomized to treatment with aripiprazole (initiated at 2 mg/d, titrated to a maximum dose of 30mg/d at day 28) or placebo after screening, wherein patients maintained alcohol abstinence for 3 days or more. The primary efficacy measure was the percentage of days abstinent over 12 weeks. Discontinuations (40.3% vs 26.7%) and treatment-related adverse events (82.8% vs 63.6%) were higher with aripiprazole than with placebo. Mean percentage of days abstinent was similar between aripiprazole and placebo (58.7% vs 63.3%; P = 0.227). Percentage of subjects without a heavy drinking day and the time to first drinking day were also comparable between groups, although the aripiprazole group had fewer drinks per drinking day (4.4 vs 5.5 drinks; P < 0.001). The aripiprazole group showed a larger decrease in percent carbohydrate-deficient transferrin, a biomarker of heavy alcohol consumption at weeks 4 (−14.91% vs −2.23%; P = 0.020) and 8 (−16.92% vs −5.33%; P = 0.021), although not at week 12 (−9.06% vs −4.12%; P = 0.298). At study end point, aripiprazole-treated subjects reported more positive subjective treatment effects and less overall severity of alcohol dependence than placebo-treated subjects. Although there was no difference between aripiprazole and placebo on the primary end point, possibly because of dose-related attrition, effects on the secondary outcomes suggest that further study of aripiprazole for treatment of alcohol dependence may be warranted at lower doses.

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 approximately 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.