First Non-Antipsychotic Treatment for Agitation Associated with Alzheimer Disease Dementia Approved by FDA
KEY TAKEAWAYS
- Auvelity is the first FDA-approved non-antipsychotic treatment for agitation associated with Alzheimer disease dementia.
- Approval was supported by randomized trials demonstrating improvements in agitation and delayed relapse of symptoms.
The Food and Drug Administration (FDA) has approved Auvelity (dextromethorphan hydrobromide and bupropion hydrochloride; Axsome Therapeutics, New York, NY) for the treatment of agitation associated with dementia due to Alzheimer disease (AD) in adults. The approval marks the first indication for this condition that is not an antipsychotic and expands the use of Auvelity—an N-methyl D-aspartate (NMDA) receptor antagonist, sigma-1 receptor agonist, and aminoketone CYP2D6 inhibitor—beyond its initial approval in 2022 for major depressive disorder. Agitation is a frequent and burdensome neuropsychiatric symptom affecting most people with AD and contributing to caregiver strain, institutionalization, and disease progression.
Key Findings
The FDA’s decision to approve Auvelity was based on a clinical program that included randomized controlled trials evaluating both short-term efficacy and longer-term durability of response. In the 5-week, phase 2/3 ADVANCE-1 clinical trial (NCT03226522), Auvelity treatment demonstrated statistically significant improvement in agitation symptoms compared with placebo, as measured by Cohen-Mansfield Agitation Inventory (CMAI) total score. In the same study, a significantly greater proportion of participants treated with Auvelity were rated as improved on the modified Alzheimer’s Disease Cooperative Study–Clinical Global Impression of Change (mADCS-CGIC) scale compared with placebo.
In the phase 3 randomized withdrawal ACCORD-2 study (NCT04947553), participants who continued treatment with Auvelity experienced a significantly longer time to relapse of agitation symptoms compared with those switched to placebo.
“The approval of Auvelity is a significant advancement that provides patients and their caregivers with a much-needed treatment option for this debilitating condition,” said George Grossberg, MD, Professor and Director of the Division of Geriatric Psychiatry at the Saint Louis University School of Medicine.
The safety profile of Auvelity was consistent with previous findings, with common adverse events including dizziness and dyspepsia. Auvelity’s label includes a Boxed Warning for increased risk of suicidal thoughts and behaviors associated with antidepressants, as well as risks of seizures, hypertension, and neuropsychiatric effects.
Sources
Axsome Therapeutics. Axsome therapeutics announces FDA approval of Auvelity (dextromethorphan HBr and bupropion HCI) for the treatment of agitation associated with dementia due to Alzheimer’s disease. Globe Newswire. Published April 30, 2026. Accessed May 1, 2026. https://axsometherapeuticsinc.gcs-web.com/node/12901/pdf
U.S. Food & Drug Administration. FDA approves first non-antipsychotic drug to treat agitation associated with dementia. Published April 30, 2026. Accessed May 1, 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-first-non-antipsychotic-drug-treat-agitation-associated-dementia?utm_medium=email&utm_source=govdelivery