Brexpiprazole shows promise in reducing agitation due to Alzheimer’s dementia

Treatment with brexpiprazole at either 2 or 3 mg significantly reduced agitation compared with placebo in patients with Alzheimer’s dementia, according to the Trial 331-14-213* presented at AAIC 2022.

“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. However, currently, there are no FDA-approved pharmacological treatments for agitation in this patient population,” said Dr George Grossberg from the Department of Psychiatry and Behavioral Neuroscience at Saint Louis University School of Medicine in St. Louis, Missouri, US.

Hence, following two prior clinical trials of brexpiprazole for the treatment of agitation in Alzheimer’s dementia, Grossberg and his team sought to confirm the efficacy, safety, and tolerability of two fixed doses of brexpiprazole (2 and 3 mg/day) in this patient population.

This multicentre, double-blind, phase III trial involved 345 patients with dementia of Alzheimer’s type who had clinically significant agitation at baseline. Participants were randomized to receive either brexpiprazole (n=228, mean age 74.5 years; 2 mg/day [n=75] or 3 mg/day [n=153]) or placebo (n=117, mean age 73.0 years) for a 12-week treatment period. [AAIC 2022, abstract HO-5-08]

At 12 weeks, patients who received either dose of brexpiprazole had a statistically significant improvement in agitation, as measured using CMAI** total score, than those who received placebo (least squares [LS] mean change from baseline, -22.6 vs -17.30; p=0.0026).

When assessed individually, both the brexpiprazole 2 mg (p=0.024) and 3 mg (p=0.005) doses significantly improved CMAI score compared with placebo.

Compared with placebo recipients, brexpiprazole recipients also achieved statistically significant improvements in CMAI subscale scores for aggressive (-9.09 vs -7.13; p=0.0040), physically nonaggressive (-6.45 vs -5.04; p=0.0296), and verbally agitated behaviours (-4.39 vs -3.14; p=0.0113).

There was also a statistically significant improvement in CGI-S*** score, as related to agitation, among those treated with brexpiprazole compared with placebo at 12 weeks (LS mean change from baseline, -1.22 vs -0.93; p=0.0055).

Treatment-emergent adverse events (TEAEs) occurred at a slightly higher rate in the brexpiprazole arm than the placebo arm (41.0 percent vs 31.0 percent), but serious TEAEs occurred at a similar rate between the two treatment arms (2.7 percent vs 2.6 percent).

Headache was the only AE that occurred at an incidence of ≥5 percent in both treatment arms. “Brexpiprazole was generally safe and well-tolerated, and no new safety signals were observed,” Grossberg noted.

“[Overall,] brexpiprazole treatment resulted in … a statistically significantly greater reduction in agitation and improvement in CGI of agitation [compared with placebo],” said Grossberg.

The findings of this current study were consistent with that observed in previous brexpiprazole studies in patients with aggressive agitation at baseline, he added.

*Trial 331-14-213: A trial to evaluate the safety, efficacy, and tolerability of brexpiprazole in treating agitation associated with dementia of the Alzheimer's type

**CMAI: Cohen-Mansfield Agitation Inventory

***CGI-S: Clinical Global Impression – Severity