Choosing Between Approved Therapies: Differentiation, Sequencing, and Black Box Warning Navigation in Alzheimer's Disease Agitation

In 'Choosing Between Approved Therapies: Differentiation, Sequencing, and Black Box Warning Navigation in Alzheimer's Disease Agitation,' the expert neurologists examined the following critical questions: In your practice, how are you differentiating antipsychotic therapies from dextromethorphan-bupropion for patients with Alzheimer's disease agitation? With the introduction of 2 Food and Drug Administration (FDA)-approved therapies in the last few years, how are you sequencing treatments in patients with Alzheimer's disease agitation?How are you navigating black box warnings with certain therapies? Alireza Atri and Anton Porsteinsson discussed how the availability of two approved agents has meaningfully changed the treatment conversation, emphasizing that both brexpiprazole and dextromethorphan-bupropion offer proven efficacy with more favorable adverse event profiles than the off-label alternatives that have historically dominated clinical practice. Dr. Atri highlighted key differentiating factors in agent selection, noting that while brexpiprazole as an atypical antipsychotic carries a black box warning for increased mortality in elderly patients with dementia-related psychosis, it is specifically indicated for agitation rather than psychosis, and that clinicians must clearly communicate this distinction to patients and families during shared decision-making conversations. He outlined the titration schedules for both agents, stressing that neither should be treated as a as-needed medication, that therapeutic benefit typically emerges over 6 to 8 weeks on average for brexpiprazole, and that contraindications for dextromethorphan-bupropion including seizure risk, hyponatremia, elevated blood pressure, serotonin syndrome potential, and monoamine oxidase inhibitor interactions must be carefully reviewed before initiation. Dr. Porsteinsson reinforced that sequencing decisions should remain individualized and that the DICE framework continues to guide ongoing evaluation regardless of which pharmacologic agent is chosen. Throughout the conversation, the experts provided a comprehensive reflection on the field and the factors that may shape how clinicians approach care moving forward. In the next episode, 'Access, Coverage, and Final Reflections on Managing Alzheimer's Disease Agitation,' panelists share their insights on insurance coverage challenges with the two Food and Drug Administration (FDA)-approved therapies, best practices for working with payers to secure patient access, and their final reflections on the management of Alzheimer's disease agitation.