Brexpiprazole Improves Agitation Symptoms in Alzheimer Dementia in 12 Weeks

Patients with Alzheimer dementia experienced a significant improvement in agitation symptoms with brexpiprazole compared to placebo, for according to study findings in published in JAMA Neurology. 

A common manifestation of Alzheimer dementia is agitation, which is characterized by excess motor activity, verbal aggression, or physical aggression. Some atypical antipsychotics are used off-label to treat agitation in dementia, but the benefit-to-risk ratio appears to be unfavorable. 

Researchers conducted a phase 3, multicenter, 12-week, randomized, double-blind, placebo-controlled, parallel-arm study (ClinicalTrials.gov Identifier: NCT03548584) to determine if brexpiprazole, an atypical antipsychotic, is safe and efficacious in treating agitation in dementia. 

Study participants with Alzheimer disease were enrolled from international clinical trial sites in Europe and the United States. Patients were aged 55 to 90 and had a diagnosis of Alzheimer disease and agitation. Some exclusion criteria were dementia or memory loss due to non-Alzheimer disease (AD) reasons or clinically significant neurologic and psychiatric conditions.

The researchers assessed patients using various scales, including the Cohen-Mansfield Agitation Inventor (CMAI) score and the Clinical Global Impression Severity of Illness (CGI-S) score, with higher scores indicating more severe agitation and illness.

A total of 345 patients were included in the study, with 288 randomly assigned to receive brexpiprazole and 117 to receive placebo. The 288 participants who received brexpiprazole were further randomly assigned in a 1:2 ratio to receive either 2 mg daily or 3 mg daily. The 3 mg dose was recommended by the US Food and Drug Administration (FDA) for investigation to determine the safety and efficacy of this higher dose. 

The average age of study participants was 74.0 and 56.5% were women. A total of 198 patients taking brexpiprazole completed the trial and 104 for placebo. 

The researchers found that brexpiprazole at both doses significantly improved the change in CMAI total score compared to placebo from baseline to 12 weeks (least-squares mean difference, -5.32; 95% CI, -8.77 to -1.87; P =.003; Cohen d effect size, 0.35).

When compared to placebo, brexpiprazole at both doses also showed a greater improvement in CGI-S score (Cohen d effect size, 0.31).

The exploratory endpoint showed a nominally significant improvement among patients taking brexpiprazole at both doses compared to placebo when using the NPI-NH total score. 

A total of 92 patients reported treatment-emergent adverse events (TEAEs) with brexpiprazole at both doses and 36 with placebo. There were no TEAEs with an incidence of 5% or more in patients taking brexpiprazole and the incidence was greater than in the placebo group. 

“Based on the results of this trial, together with a previous trial, brexpiprazole was approved in the United States for the treatment of agitation associated with dementia due to Alzheimer disease,” the researchers noted. 

Study limitations are differences in the standard of care for dementia across countries, some assessments relying on caregiver observation, and the lack of generalizability to certain populations. 

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.