Background Agitation in Alzheimer's disease significantly impacts patient outcomes and caregiver burden. Brexpiprazole has emerged as a promising treatment option, but optimal dosing remains unclear. Objective To evaluate the comparative efficacy and safety of different brexpiprazole doses in treating agitation associated with Alzheimer's disease through a systematic review and network meta-analysis (NMA). Methods Following PRISMA guidelines, we searched PubMed, Embase, Web of Science, and Scopus through January 2025. Four randomized controlled trials (N = 1451) comparing various brexpiprazole doses (0.5–3 mg/day) with placebo were included. Primary outcomes included changes in the Cohen-Mansfield Agitation Inventory (CMAI), the Clinical Global Impression-Severity Scale (CGI-S), and the Neuropsychiatric Inventory-Nursing Home Version (NPI-NH) scores, alongside safety measures. Results Brexpiprazole 2 mg demonstrated significant improvement in CMAI scores versus placebo (mean difference MD: −5.88; 95% CI: −8.13 to −3.63) and CGI-S scores (MD: −0.48; 95% CI: −0.95 to −0.01). Multiple doses showed significant NPI-NH improvements, with 2–3 mg showing the strongest effect (MD: −4.60; 95% CI: −7.54 to −1.66). Higher doses (2–3 mg) increased treatment-emergent adverse events (risk ratio RR: 1.20–1.33) but showed no significant difference in serious adverse events compared to placebo. Conclusions Brexpiprazole 2 mg provides optimal therapeutic benefit while maintaining a favorable safety profile. The findings support initiating treatment at lower doses with careful titration to 2 mg based on individual response and tolerability. Future research should focus on long-term outcomes and real-world effectiveness.
Kandeel et al. (Mon,) studied this question.
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