New REXULTI® Efficacy Insights for Alzheimer’s-Related Dementia Agitation

Recent studies indicate that REXULTI (brexpiprazole) has been linked to a decrease in the overall symptoms of neuropsychiatric conditions and specifically agitation in patients with dementia caused by Alzheimer's disease. The drug demonstrated its effectiveness in reducing agitation symptoms within the first four weeks of treatment and showed consistent results across various factors such as the severity of dementia, the environment of care, and the use of other medications.

REXULTI is the first medication to be approved by the U.S. Food and Drug Administration (FDA) for the treatment of agitation associated with Alzheimer's disease-related dementia. This condition affects about half of all dementia patients and is characterized by behaviors like pacing, shouting, and physical aggression, which can be highly distressing for both patients and caregivers.

At the American Association for Geriatric Psychiatry (AAGP) 2024 Annual Meeting, Otsuka Pharmaceutical Development & Commercialization, Inc. and Lundbeck U.S. presented three posters detailing the results of post hoc pooled analyses from two pivotal Phase 3 trials. These analyses revealed that REXULTI not only reduced neuropsychiatric symptoms but also lessened the disruptiveness of patients' behavior, which in turn alleviated caregiver distress.

The Neuropsychiatric Inventory (NPI), a tool used to assess the frequency and severity of neuropsychiatric symptoms, was employed in one of the posters to demonstrate the drug's impact. The findings showed that REXULTI led to a significant reduction in the NPI scores, indicating an improvement in agitation symptoms compared to placebo.

Another poster examined the drug's efficacy across different patient subgroups, including those with varying degrees of dementia severity and those receiving different care settings or medications. A responder analysis, which measures the change in the Cohen-Mansfield Agitation Inventory (CMAI) total score, showed that REXULTI was more effective than placebo in improving agitation symptoms.

The final poster focused on the efficacy and safety of REXULTI in patients with and without psychosis symptoms at baseline. The results indicated that fixed doses of REXULTI led to greater improvements in agitation symptoms compared to placebo, and the safety profile of the drug was consistent between the two subgroups.

Experts in the field, such as George T. Grossberg, MD, have emphasized the importance of these findings, as they highlight the potential positive impact of treating agitation symptoms on caregiver distress. The data also support the separate treatment of agitation from dementia and provide prescribers with confidence in choosing an FDA-approved therapy.

Brexpiprazole, the active ingredient in REXULTI, was discovered by Otsuka and is being co-developed by Otsuka and Lundbeck. Its mechanism of action is not fully understood but is believed to involve partial agonist activity at certain serotonin and dopamine receptors, as well as antagonist activity at serotonin receptors.

REXULTI is indicated for use alongside antidepressants to treat major depressive disorder in adults, for the treatment of schizophrenia in adults and children over 13, and for the treatment of agitation associated with Alzheimer's disease dementia. However, it is not intended for the "as needed" treatment of agitation or for use in children with MDD or under 13 with schizophrenia.

The safety information for REXULTI includes warnings about the increased risk of death in elderly patients with dementia-related psychosis, the potential for suicidal thoughts and actions, and serious side effects such as cerebrovascular problems, neuroleptic malignant syndrome, uncontrolled body movements, and metabolic issues. It is crucial for patients and healthcare providers to be aware of these risks and monitor for any changes in symptoms or side effects.