Work

Brexpiprazole for Individual Agitation Symptoms in Alzheimer’s Dementia: A Caregiver-Centered Post Hoc Analysis

Year: 2026

Type: article

Abstract: People with Alzheimer’s dementia commonly experience agitation symptoms, which are distressing to caregivers and can influence long-term care decisions. The aim of this exploratory post hoc analysis was to test the hypothesis that brexpiprazole can improve individual agitation symptoms over 12 and 24 weeks, including symptoms that caregivers find the most distressing. Data were included from two phase 3, 12-week, randomized (brexpiprazole or placebo), double-blind trials and a phase 3, 12-week, brexpiprazole-treatment extension trial. Participants had Alzheimer’s dementia with agitation, and lived at home or in long-term care. The frequency of 29 agitation symptoms over 12 and 24 weeks was assessed using Cohen-Mansfield Agitation Inventory (CMAI) item scores. The focus of this post hoc analysis was the 11 CMAI agitation symptoms that caregivers found the most distressing in a prior survey. Among 610 participants (median age 74 years, 55.5% female, 44.5% male), each of the 11 most-distressing agitation symptoms reduced in frequency from baseline to Week 12, with further improvements to Week 24 (n = 159). Improvements over 12 weeks were numerically greater with brexpiprazole 2 or 3 mg/day (n = 363) compared with placebo (n = 247) on 9 of 11 symptoms: cursing or verbal aggression, spitting, repetitive sentences or questions, hitting, constant unwarranted requests for attention/help, trying to get to a different place, pacing or aimless wandering, grabbing onto people or things, and kicking. Each of the 18 other agitation symptoms (beyond the most distressing) also reduced in frequency. After 24 weeks, 15 of 29 agitation symptoms occurred less than once a week. Brexpiprazole was associated with improvement in a range of agitation symptoms in people with Alzheimer’s dementia, including those that are the most distressing to caregivers. These exploratory results suggest that brexpiprazole may improve the specific agitation symptoms that can have the biggest impact on the caregiver experience. ClinicalTrials.gov identifiers: NCT01862640, NCT03548584, NCT03594123. Alzheimer’s dementia is a brain disease that gradually affects people’s thinking, memory, and behavior. People with Alzheimer’s dementia commonly experience a range of agitation symptoms, such as restlessness, repetitive questions, wandering, shouting, swearing, and kicking. Some of these symptoms are particularly difficult for caregivers to manage, and may be factors in the decision to move a person with dementia from home into long-term care. Previous studies have shown that a medicine called brexpiprazole can improve people’s overall level of agitation. In this study, researchers looked at whether brexpiprazole can improve the specific agitation symptoms that caregivers find the most distressing. This was done by re-analyzing data from existing clinical studies in which 610 people were given brexpiprazole or placebo (which has no medicine in it) at random. The results showed that brexpiprazole can improve a range of different agitation symptoms over 12 weeks, including 9 of the 11 symptoms that are the most distressing to caregivers. Another analysis showed that many agitation symptoms occurred less than once a week in 159 people treated with brexpiprazole for 24 weeks. Overall, this study shows that brexpiprazole can help with the agitation symptoms that caregivers may find the hardest to manage on their own.

Source: Neurology and Therapy

DOI: 10.1007/s40120-026-01037-4