Brexpiprazole Shows Consistent Efficacy Across Subgroups in Alzheimer-Related Agitation
An exploratory, post hoc pooled analysis of two international, randomized, double-blind trials suggests that brexpiprazole at doses of 2 or 3 mg per day may offer consistent efficacy and tolerability for the treatment of agitation symptoms in patients with dementia due to Alzheimer disease. The analysis provides additional insight into how the therapy performs in diverse clinical scenarios commonly encountered in practice.
The pooled dataset included 621 adults with Alzheimer dementia and mild-to-severe cognitive dysfunction who exhibited agitation. Participants received either brexpiprazole (2 or 3 mg/day) or placebo for 12 weeks. Agitation was assessed using the Cohen-Mansfield Agitation Inventory (CMAI), with safety outcomes measured through treatment-emergent adverse events (TEAEs). Investigators examined 13 clinically relevant subgroups based on care setting, cognitive severity, behavioral comorbidities, and use of concomitant medications for dementia and psychiatric conditions.
Brexpiprazole demonstrated numerically greater reductions in agitation frequency than placebo in 12 of 13 subgroups. The only exception was the small subgroup of patients receiving concomitant benzodiazepines (n = 71), although efficacy was observed for this group in secondary analyses. The largest differences favoring brexpiprazole were seen among patients using concomitant antidepressants and those with co-occurring sleep disorders or psychosis—groups that often present significant treatment challenges in long-term care and memory care settings.
Patients treated with brexpiprazole also showed improvements in overall symptom severity, reflected by lower Clinical Global Impression–Severity (CGI-S) scores, regardless of care environment or degree of cognitive impairment. Across subgroups, a higher proportion of brexpiprazole-treated participants achieved clinically meaningful responses, consistent with what the authors describe as “an important, noticeable improvement in agitation.”
The incidence of TEAEs was comparable across subgroups, indicating that brexpiprazole’s safety profile remained stable across a range of patient types and concomitant medication use. No new safety concerns emerged, and adverse events were generally consistent with those previously observed in the parent trials.
For clinicians managing patients in long-term care or community settings, this consistency is clinically significant. The ability to maintain efficacy and tolerability across varying levels of cognitive function and behavioral comorbidity suggests brexpiprazole may offer a flexible option for addressing agitation—a symptom known to increase caregiver burden, accelerate institutionalization, and complicate dementia management.
These findings support brexpiprazole’s utility in routine care of patients with Alzheimer-related agitation, extending beyond controlled trial conditions. In practice, many individuals present with overlapping neuropsychiatric symptoms or are treated with multiple medications, factors that often complicate pharmacologic decision-making. The current analysis provides clinicians with reassurance that brexpiprazole’s efficacy and safety are not confined to narrowly defined patient populations.
For long-term care physicians, the data suggest that brexpiprazole may represent a viable therapeutic option across a broad spectrum of patients, including those with coexisting behavioral symptoms or concurrent dementia medications. Continued research will help define optimal patient selection and confirm these findings in real-world practice, but this analysis reinforces the potential of brexpiprazole to address one of the most challenging behavioral manifestations of Alzheimer disease.
Reference
Stroud J, Cumming JL, Chumki SR, et al. Brexpiprazole for agitation in clinically relevant patient subgroups: a post hoc analysis of efficacy and safety in patients with agitation associated with dementia due to Alzheimer’s disease. Curr Med Res Opin. 2025;41(8):1523-1534. doi: 10.1080/03007995.2025.2552278
