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And now, the FDA approves a medication for behavioral symptoms of Alzheimer’s disease

David Sultzer, MD

David Sultzer, MD

May 12, 2023–Brexpiprazole has now been approved by the FDA for the treatment of agitation in Alzheimer’s dementia.  Agitated behaviors are common in those with moderate or advanced Alzheimer’s dementia and these symptoms contribute substantially to caregiver burden, institutionalization, and faster cognitive decline.  Yesterday’s decision marks the first approval in the United States of a medication for these symptoms.

The approval was based on the results of three 12-week treatment studies.  The studies collectively showed modest reduction in the frequency of specific agitated behaviors and lower severity on a clinician-rated measure.  In one of the studies, 56% of those treated with brexpiprazole met a threshold for meaningful improvement, compared to 37% of those treated with placebo.  Benefit was apparent across the three main types of agitated behaviors: aggressive, physically non-aggressive, and verbally agitated, although none were eliminated with treatment.  There were some side effects with brexpiprazole treatment – headache, dizziness, sedation – although these effects were not common in these relatively short-term trials.

This is a step forward for those with Alzheimer’s dementia and their families.  Historically, antipsychotic medications have been used to treat various behavioral symptoms, despite limited evidence of benefit and well-known risks of treatment, including mortality.  While it’s not possible to fully compare brexpiprazole’s beneficial and adverse effects with other antipsychotic drugs, some of the common adverse effects of antipsychotic treatment such as muscle rigidity and falls did not seem to occur in the brexpiprazole trials.  These trials also reflect some improvements in the quality of behavioral symptom trials, with careful inclusion criteria, valid measures of target symptoms, and convergent findings across several trials.

There are still important questions to be answered: Which specific behavioral symptoms respond best to treatment?  What are the side effects (and potential benefits) of treatment longer than 12 weeks?  How can medication treatments be integrated with important behavioral strategies, such as environmental adjustments and caregiver education and support, to best address agitated behaviors?

Like the recent accelerated approval of two anti-amyloid antibody treatments for early AD, the brexpiprazole approval represents an incomplete solution to the causes and symptoms of this debilitating disorder.  However, they are important next-steps in the evolution of Alzheimer’s interventions and the brexpiprazole approval helps to broaden the treatment landscape to include the disabling behavioral symptoms of the illness.