Axsome's Auvelity Gains FDA Approval as First Non-Antipsychotic for Alzheimer's Agitation, Challenging Rexulti

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On April 30, 2026, the FDA approved Auvelity (dextromethorphan-bupropion) for treating agitation associated with Alzheimer's disease dementia in adults, marking it as the first non-antipsychotic option.1234

Auvelity, initially approved in 2022 for major depressive disorder, targets NMDA and sigma-1 receptors and showed significant improvements in agitation scores and relapse prevention in two Phase 3 trials (ADVANCE-1 and ACCORD-2).124

Unlike Rexulti (brexpiprazole), approved in 2023 for the same indication, Auvelity lacks a black box warning for increased mortality in elderly dementia patients, positioning it as a potential first-line treatment.12

Auvelity was well-tolerated with common side effects like dizziness and indigestion, no sedation or cognitive decline observed.123

Analysts project Auvelity could achieve peak sales over $2.1 billion in Alzheimer's agitation, a market previously holding only 4.6% by Rexulti in 2025.1

Sources:

1. https://medcitynews.com/2026/05/axsome-alzheimers-disease-agitation-auvelity-fda-approval-axsm/

2. https://www.clinicaltrialsarena.com/analyst-comment/auvelity-first-non-antipsychotic-alzheimers-agitation/

3. https://www.alz.org/news/2026/alzheimers-association-welcomes-fda-approval-treatment-for-agitation

4. https://www.fda.gov/news-events/press-announcements/fda-approves-first-non-antipsychotic-drug-treat-agitation-associated-dementia