Efficacy of Brexpiprazole in Participants with Agitation Associated with Dementia Due to Alzheimer's Disease: Pooled Analysis of Randomized Controlled Trials.

OBJECTIVE: This analysis aimed to evaluate the efficacy of brexpiprazole 2 or 3 mg/day for the treatment of agitation associated with dementia due to Alzheimer's disease, on the basis of pooled clinical trial data. METHODS: Data were pooled from two similarly designed, phase 3, 12-week, multicenter, randomized, double-blind, placebo-controlled trials of fixed-dose brexpiprazole in participants in care facilities or community-based settings who had agitation associated with dementia due to Alzheimer's disease. Efficacy outcomes included Cohen-Mansfield Agitation Inventory (CMAI) total score (which measures the frequency of 29 different agitation symptoms), Clinical Global Impression-Severity of illness (CGI-S) score, CMAI factor scores (aggressive behaviors, physically nonaggressive behaviors, and verbally agitated behaviors), and response rates. A sensitivity analysis included a third trial with flexible dosing. RESULTS: In total, 621 participants were randomized (brexpiprazole, 368; placebo, 253), and completion rates were 320/368 (87.0%) and 225/253 (88.9%), respectively. Mean (SD) baseline CMAI total scores were: brexpiprazole 76.9 (17.2) points and placebo 75.5 (18.0) points. Over 12 weeks, CMAI total scores improved by least squares mean (SE) - 22.8 (0.8) points for brexpiprazole and - 18.3 (1.0) points for placebo, with a least squares mean difference between treatment arms of - 4.50 points (95% CI - 6.90 to - 2.10; p < 0.001; Cohen's d 0.30). CGI-S, CMAI factor, and response analyses also showed greater improvement with brexpiprazole versus placebo. The sensitivity analysis was supportive. CONCLUSIONS: Brexpiprazole 2 or 3 mg/day reduced agitation symptoms compared with placebo over 12 weeks in this large, pooled sample of participants with dementia due to Alzheimer's disease. STUDY REGISTRATION: ClinicalTrials.gov identifiers: NCT01862640, NCT03548584, and NCT01922258. Many people with Alzheimer’s dementia experience agitation as well as a decline in their memory and ability to think. Agitation can take a variety of forms, including movement-related agitation (such as pacing or restlessness), verbal agitation (such as shouting or swearing), and aggression (such as grabbing or shoving). Agitation can make life difficult for the person with Alzheimer’s dementia and for the people caring for them. Some people may need medicine for their agitation. Large clinical trials have investigated the effects of brexpiprazole, an atypical antipsychotic medicine, on agitation in people with Alzheimer’s dementia. In this analysis, researchers combined information from different trials to gain a comprehensive picture of brexpiprazole for the treatment of agitation. Agitation was measured using questionnaires that were completed by doctors on the basis of discussions with caregivers. The results showed that brexpiprazole improved overall agitation frequency as well as the frequency of specific types of agitation, including movement-related agitation, verbal agitation, and aggression. This means that brexpiprazole may be an effective treatment for agitation in people with Alzheimer’s dementia.