Brexpiprazole With Antidepressants for Agitation in Alzheimer's Dementia: Post Hoc Analysis

To analyze the efficacy and safety of brexpiprazole versus placebo on agitation symptoms in participants with Alzheimer's dementia, with and without concomitant antidepressants.

Data were pooled from two Phase 3, 12-week, randomized, double-blind, placebo-controlled trials of brexpiprazole (ClinicalTrials.gov identifiers: NCT01862640, NCT03548584). Post hoc, participants were stratified by antidepressant use. Efficacy was assessed using the Cohen-Mansfield Agitation Inventory (CMAI) and safety using treatment-emergent adverse events (TEAEs).

Brexpiprazole 2 or 3 mg/day improved CMAI Total score versus placebo in participants with concomitant antidepressant (n = 97; least squares mean difference at Week 12, -12.1 [95% confidence interval, -19.1 to -5.05]; t₍₇₇₎ = -3.4, p = 0.001; Cohen's d = 0.72) and without concomitant antidepressant (n = 513; -2.93 [-5.49 to -0.37]; t₍₄₈₇₎ = -2.2, p = 0.025; Cohen's d = 0.20). Falls were the only TEAE reported for ≥5% of participants with concomitant antidepressant (brexpiprazole, 6.5%; placebo, 5.7%).

In this exploratory post hoc analysis, brexpiprazole improved agitation symptoms and was generally well tolerated in participants with Alzheimer's dementia with and without concomitant antidepressants.