Efficacy and Safety of Brexpiprazole for Agitation in Alzheimer’s Disease: A Systematic Review and Meta-Analysis

Abstract Objective: Agitation in Alzheimer’s disease (AD) worsens patient quality of life and increases caregiver burden. Brexpiprazole, a serotonin-dopamine activity modulator, is a potential treatment, but its efficacy and safety remain unclear. This study was conducted to evaluate brexpiprazole’s efficacy and safety for AD-related agitation via a systematic review and meta-analysis. Methods: A systematic search identified randomized controlled trials (RCTs). Primary outcome: Cohen-Mansfield Agitation Inventory (CMAI). Secondary outcomes: Clinical Global Impression-Severity (CGI-S), Neuropsychiatric Inventory-Nursing Home (NPI-NH), adverse events, and discontinuation rates. Data were pooled using a random-effects model, and certainty of evidence was assessed using GRADE. Results: Five RCTs (1,413 participants) showed brexpiprazole significantly reduced CMAI (MD: -3.89, p = 0.0001) and CGI-S (MD: -0.29, p = 0.002) with moderate to high certainty. NPI-NH was not significant. Adverse events were slightly higher (RR: 1.12, p = 0.04). Conclusion: Brexpiprazole reduces agitation symptoms in AD, particularly CMAI and CGI-S scores, with moderate to high certainty of evidence. However, its increased risk of adverse events necessitates careful patient selection and monitoring. Further long-term studies are needed. PROSPERO Registration number: CRD42024622841