FDA Approves Brexpiprazole for Agitation Associated With Dementia Related to Alzheimer Disease

The FDA has approved brexpiprazole (Rexulti; Otsuka Pharmaceutical Company Ltd, Lundbeck Inc.) as the first treatment indicated for agitation associated with dementia due to Alzheimer disease. At 12 weeks, brexpiprazole 2 mg or 3 mg was associated with a statistically and clinically meaningful improvement in agitative behaviors caused by dementia compared to placebo, according to the results of a recent placebo-controlled study.

“Agitation is one of the most common and challenging aspects of care among patients with dementia due to Alzheimer disease,” said Tiffany Farchione, MD, director of the Division of Psychiatry in the FDA’s Center for Drug Evaluation and Research, in a press release.

Agitation can be pacing, restlessness, and aggression (verbal and physical).

“These symptoms are leading causes of assisted living or nursing home placement and have been associated with accelerated disease progression,” Farchione said.

Investigators conducted a pair of 12-week, randomized, double-blind, placebo-controlled, fixed-dose studies to evaluate the safety and efficacy of brexpiprazole for agitation associated with dementia related to Alzheimer disease. Investigators enrolled patients with probable diagnosis of Alzheimer dementia (aged 51 to 90 years), a score between 5 and 22 on the Mini-Mental State Examination, and certain agitation behaviors that require medication.

In the first study, patients received 1 or 2 mg of brexpiprazole and for the second, patients received 2 or 3 mg of brexpiprazole. The primary outcome of both studies was change of score on the Cohen-Mansfield Agitation Inventory total (CMAI) from baseline to week 12. CMAI scores—which rates the frequency of agitative behaviors in patients with dementia—improved with 2 mg and 3 mg of brexpiprazole compared to placebo.

Patients are recommended to start at a dosage of 0.5 mg once daily for 1 week. Dosage can increase to 1 mg once daily during week 2 (days 8-14) and 2 mg on day 15. Although the target dose is 2 mg, it can increase to a maximum of 3 mg once daily after 14 days, based on tolerability and clinical response.

The most common adverse events (AEs) include headache, dizziness, urinary tract infection, nasopharyngitis, and sleep disturbances (somnolence and insomnia). Brexpiprazole will have a Boxed Warning that states this medication class increases the risk of death in older adults with dementia-related psychosis who are treated with antipsychotic drugs.

More than 6.5 million people in the United States have Alzheimer disease, which is the leading cause of dementia. Dementia is a serious and debilitating neurological condition characterized by a progressive decline of 1 or more cognitive domains in the brain. Dementia causes psychological and behavioral disturbances—the most common is agitation, which is a persistent, complex, stressful, and costly result of the brain disorder.

Brexpiprazole received FDA Fast Track designation because it treats a serious condition and fills an unmet medical need.

Reference

FDA. FDA Approves First Drug to Treat Agitation Symptoms Associated with Dementia due to Alzheimer’s Disease. News Release. May 11, 2023. Accessed on May 1, 2023. https://www.fda.gov/news-events/press-announcements/fda-approves-first-drug-treat-agitation-symptoms-associated-dementia-due-alzheimers-disease