Brexpiprazole safe, effective to treat agitation in Alzheimer’s-related dementia

SAN DIEGO — In older adult patients with Alzheimer’s-related dementia, treatment with brexpiprazole resulted in greater reduction in agitation compared with placebo, while proving to be safe and well-tolerated.

“Agitation is a prevalent clinical manifestation of Alzheimer’s dementia and is one of the most stressful aspects of care in patients affected by the disease,” George T. Grossberg, MD, professor of psychiatry at Saint Louis University School of Medicine, wrote in a presentation made at the Alzheimer’s Association International Conference.

“However, currently, there are no FDA-approved pharmacological treatments for agitation in this patient population.”

Following two prior clinical trials of brexpiprazole in this patient population, Grossberg and colleagues sought to confirm the efficacy, safety and tolerability of brexpiprazole in patients with agitation in Alzheimer’s dementia.

The trial was a 12-week, multicenter, randomized, double-blind, placebo-controlled, parallel-arm study that included 345 patients aged 55 to 90 years, in care facilities or community-based setting, had a diagnosis of probable Alzheimer’s disease and met criteria for agitation as defined by the International Psychogeriatric Association. Participants were randomized on a 2:1 basis to either brexpiprazole or placebo; within the brexpiprazole group, participants were further randomized 1:2 to either fixed dose of 2 mg per day or 3 mg per day.

Stable background medications for the treatment of Alzheimer’s disease were permitted. The primary endpoint was change from baseline to week 12 in Cohen–Mansfield Agitation Inventory (CMAI) total score, with the secondary endpoint change from baseline to week 12 in Clinical Global Impression Severity of illness (CGI-S) score, as related to agitation. Safety was additionally assessed.

Results showed that the mean change from baseline to Week 12 in CMAI total score was statistically significantly greater in the brexpiprazole group compared with the placebo group. Statistically significant separation between the brexpiprazole and placebo groups was also observed on the key secondary endpoint of change from baseline to week 12 in CGI-S score. Aside from headache (6.6%), no other treatment-emergent adverse events occurred with an incidence 5% in the brexpiprazole cohort.

“We are incredibly grateful to all the patients with Alzheimer's dementia, their families and the investigators who participated in the trials and contributed greatly to this research,” Johan Luthman, PhD, executive vice president and head of research and development at Lundbeck, said in a release that accompanied the study.

Reference:

• Otsuka Pharmaceutical and Lundbeck present positive results showing reduced agitation in patients with Alzheimer’s dementia treated with brexpiprazole at the 2022 Alzheimer's Association International Conference. Published Aug 4, 2022. Accessed Aug. 11, 2022.