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 Aug 23:1-16. doi: 10.1080/03007995.2025.2552278. Online ahead of print.

ABSTRACT

OBJECTIVE: To explore the efficacy and safety of brexpiprazole for the treatment of agitation symptoms in clinically relevant subgroups of patients with dementia due to Alzheimer’s disease.

METHODS: Data were pooled for brexpiprazole (2 or 3 mg/day) and placebo from two international, randomized, double-blind trials in adults with a clinical diagnosis of Alzheimer’s dementia with mild-to-severe cognitive dysfunction and with agitation (ClinicalTrials.gov identifiers: NCT01862640, NCT03548584). Change in agitation frequency over 12 weeks was measured using the Cohen-Mansfield Agitation Inventory (CMAI). Safety measures included treatment-emergent adverse events (TEAEs). In this post hoc analysis, thirteen clinically relevant subgroups were investigated based on care setting (institutionalized, non-institutionalized), severity of cognitive dysfunction (mild/moderate, severe), co-occurring behavioral symptoms (psychosis, depression, anxiety, irritability, sleep disturbance), and use of concomitant medications for dementia (acetylcholinesterase inhibitor, memantine) and psychiatric conditions (antidepressant, benzodiazepine).

RESULTS: In the randomized sample (N = 621), mean age was 74 years (range 55-90 years), 344 (55.4%) participants were female, and 277 (44.6%) were male. Over 12 weeks, brexpiprazole showed numerically greater reduction in agitation frequency than placebo in 12 of 13 subgroups. The only exception was ‘concomitant benzodiazepines’, which was a small subgroup (n = 71), but showed efficacy for brexpiprazole in secondary analyses. The largest differences in favor of brexpiprazole versus placebo were for the concomitant antidepressant, co-occurring sleep disorder, and co-occurring psychosis subgroups. The overall incidence of TEAEs was generally consistent across subgroups.

CONCLUSION: In these exploratory analyses, brexpiprazole reduced symptoms of agitation across a wide range of patients with agitation associated with dementia due to Alzheimer’s disease.

PMID:40847656 | DOI:10.1080/03007995.2025.2552278