Assessing Potential Treatment Options for Agitation in Older Adults With Alzheimer Disease: George Grossberg, MD

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“I think the next steps would be to look at the same compound in delirium. We do not have anything that's FDA-approved for delirium, or acute confusion and disorientation in older adults with or without dementia. This type of treatment would be beneficial for where we're needing to get the patient under control because of acute confusion and disorientation that is often accompanied by irritability.”

In Alzheimer disease (AD), agitation is characterized as a behavioral syndrome among patients who experience an increased, often undirected, motor activity, restlessness, aggressiveness, and emotional distress. According to a review published in Frontiers in Neurology, research shows agitation prevalence ranges from 30% to 50% in patients with AD and is the third most common neuropsychiatric symptom in dementia, following apathy and depression.¹ In the past few years, agitation incidence has increased in AD because of the COVID-19 pandemic and with that, has also increased levels of distress in patients and caregivers.

Recently, investigators published the full data set of the phase 3 Study 331-12-283 (NCT01862640) that assessed brexpiprazole (Rexulti; Otsuka/Lundbeck), the first FDA–approved agent to treat patients with Alzheimer disease (AD) agitation.² The trial featured 345 patients with AD agitation who were randomly assigned 2:1 to either brexpiprazole (n = 228) or placebo (n = 117) and assessed on change in Cohen-Mansfield Agitation Inventory (CMAI) total score, the primary end point. In the study, patients on 2 or 3 mg brexpiprazole showed statistically significant improvement vs placebo in reducing agitation symptoms over a 12-week period.

Senior author George Grossberg, MD, Samuel W. Fordyce professor and director of Geriatric Psychiatry in the Department of Psychiatry at St. Louis University School of Medicine, sat down in a recent interview with NeurologyLive® to discuss how frequently patients might be able to use BXCL501 (Igalmi; BioXcel Therapeutics), an investigational treatment for agitation, and its potential for preventive administration in chronic agitation cases. He also talked about what distinguishes this compound from existing antiagitation therapies, particularly brexpiprazole, and how it might address the unique challenges of geriatric care. In addition, Grossberg spoke about the potential implications and applications of this compound in addressing other cognitive conditions, such as delirium, in older adults.

REFERENCES
1. Carrarini C, Russo M, Dono F, et al. Agitation and Dementia: Prevention and Treatment Strategies in Acute and Chronic Conditions. Front Neurol. 2021;12:644317. Published 2021 Apr 16. doi:10.3389/fneur.2021.644317
2. Lee D, Slomkowski M, Hefting N, et al. Brexpiprazole for the Treatment of Agitation in Alzheimer Dementia: A Randomized Clinical Trial. JAMA Neurol. 2023;80(12):1307-1316. doi:10.1001/jamaneurol.2023.3810