Dose-dependent Efficacy and Safety of Brexpiprazole in Agitation Associated with Dementia in Alzheimer's Disease: A Systematic Review and Meta-analysis
Hammad Javaid1, Anurag Jha1, Umaima Cheema1, Meeram Noor1, Shamikha Cheema1, Mahnoor Arfan1, Maryyam Aqeel1, Erum Habib2, Muhammad Nabeel Saddique1, Maria Qadri3, Muhammad Moiz Javed4, Areej Riaz1
1King Edward Medical University, 2Dow University of Health Sciences, 3Jinnah Sindh Medical University, 4Geisinger College of Health Sciences
Objective:
This systematic review and meta-analysis evaluates the efficacy and safety of brexpiprazole in managing agitation associated dementia in Alzheimer's disease at different doses.
Background:
Agitation is one of the most distressing neuropsychiatric symptoms in patients with dementia due to Alzheimer’s disease (AD), significantly impacting patients' quality of life and increasing caregiver burden. Brexpiprazole, a serotonin-dopamine modulator, shows up a promising option for managing agitation.
Design/Methods:
A comprehensive literature search was conducted across PubMed, Cochrane, Scopus, Embase and ClinicalTrials.gov from inception until January 2025. We pooled dichotomous outcomes as risk ratios (RR) and continuous outcomes as mean differences (MD) with 95% confidence intervals (CI), using random-effects models. Heterogeneity was assessed using I² and X² statistics. A p-value of <0.05 was considered statistically significant. All the calculations were performed using RevMan 5.4.
Results:
This meta-analysis included 4 studies involving 1440 patients (944 vs. 496) suffering from agitation associated with dementia in AD. Brexpiprazole significantly reduced agitation on CMAI (MD: -3.94, 95% CI [-6.21 to -1.67], p<0.001) and NPI-NH (MD: -0.67, 95% CI [-1.08 to -0.26], p=0.002) with optimal efficacy at 2–3 mg/day. SAS scores increased significantly (MD: 0.38, 95% CI [0.18–0.58], p=0.0002) while MMSE (p=0.06) and CGI-S (p=0.06) remained unchanged. No significant differences emerged in serious adverse events (p = 0.57), mortality (p = 0.22), dizziness (p = 0.51) and extrapyramidal effects (p = 0.18).
Conclusions:
Brexpiprazole effectively reduces agitation in AD without major safety concerns, though mild motor effects were noted. Study limitations include moderate heterogeneity and short trial durations. Future research should explore long-term outcomes and patient stratification.
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