Brexpiprazole Demonstrates Clinically Meaningful Improvements for Agitation Due to Alzheimer Disease


In May 2023, the FDA approved brexpiprazole as the first and only drug to receive approval for treatment of agitation associated with Alzheimer Disease dementia.

Treatment with brexpiprazole (Rexulti; Otsuka Pharmaceutical Development & Commercialization Inc, Lundbeck Pharmaceuticals LLC) has demonstrated statistically significant and clinically meaningful improvements for those with agitation associated with dementia from Alzheimer disease (AD), according to results from the phase 3 Study 213 (NCT03548584).1

Memory loss due to dementia. Senior man losing parts of head as symbol of decreased mind function. | Image Credit: pathdoc -

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In May 2023, the FDA approved brexpiprazole as the first and only drug to receive approval for treatment of agitation associated with AD dementia.2 It is not indicated as an “as needed” regimen for this indication.1

“One of the most challenging aspects of caring for someone with [AD] dementia, whether it be a health care provider or loved one, is when they develop agitation symptoms that become increasingly difficult to manage alone,” George T. Grossberg, MD, from the department of Psychiatry and Behavioral Neuroscience at Saint Louis University School of Medicine, said in a statement. “The findings of this study provide evidence that brexpiprazole meets the needs of patients and their caregivers and is an efficacious, well-tolerated treatment for the often-debilitating symptoms of agitation associated with dementia due to [AD].”1

Study 213 is the second pivotal phase 3 study to report positive findings with brexpiprazole, in addition to Study 283 (NCT01862640). Individuals in the study had mild to severe dementia, defined as a score between 5 and 22 on the Mini Mental State Examination, a tool for screening of cognitive impairment in older adults. Furthermore, investigators used the Cohen-Mansfield Agitation Inventory (CMAI) aggressive behavior subscale to identify symptoms of agitation, which can include hitting, kicking, scratching, grabbing, verbal aggression, spitting, and more.1

The individuals in the study also needed a diagnosis that met The International Association’s provisional definition of agitation in individuals with cognitive impairment or dementia, including evidence of emotional distress, verbal aggression, or physical aggression, according to the statement.1

In the study, individuals received either 2 mg or 3 mg daily of brexpiprazole or the placebo. Investigators found that the drug significantly improved symptoms after 12 weeks of treatment, for both strengths, when compared to the placebo, according to the results published in JAMA Neurology. The drug improved all 3 classifications of agitation symptoms, including aggressive behavior, physically nonaggressive behavior, and verbally agitated behavior, according to the statement.1,3

Furthermore, brexpiprazole also demonstrated a 22.6-point reduction in mean CMAI total scores compared to the placebo, which had a reduction of 17.6 points in mean CMAI scores.1

Brexpiprazole was also well-tolerated in the study, demonstrating a clinical safety profile consistent of the known profile for this indication. Approximately 86.8% of individuals completed the trial in the brexpiprazole group compared to 88.9% in the placebo group. Also, from baseline to week 12, there was no indication that individual’s cognitive functions worsened during the study.1

The most common adverse events included weight gain, akathisia, headache, somnolence, anxiety, and restlessness.1

“Agitation associated with dementia due to [AD] can be very challenging and emotionally distressing for patients and family members caring for them. With the publication of the complete Study 213 data, the evidence of brexpiprazole as an effective, well-tolerated treatment for this indication will help clinicians, families, and caregivers make informed decisions about what is best for their patient or loved one who lives with this complex condition,” John Kraus, MD, PhD, executive vice president and chief medical officer at Otsuka, said in the statement.1


  1. JAMA Neurology Publishes Complete Results of Positive Phase 3 Study of REXULTI® (brexpiprazole) for Agitation Associated with Dementia Due to Alzheimer’s Disease. News release. Lundbeck. November 6, 2023. Accessed November 6, 2023. Email.
  2. Hunter, E. FDA Approves Brexpiprazole for agitation Associated with Dementia Related to Alzheimer Disease. Pharmacy Times. May 12, 2023. Accessed November 6, 2023.
  3. Lee D, Slomkowski M, Hefting N, Chen D, et al. Brexpiprazole for the Treatment of Agitation in Alzheimer Dementia: A Randomized Clinical Trial. JAMA Neurol. doi:10.1001/jamaneurol.2023.3810
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