The Approval of Auvelity, the Second Treatment for Alzheimer Disease Agitation

On April 30, 2026, the US Food and Drug Administration approved Axsome Therapeutics’ oral dextromethorphan-bupropion (Auvelity, formerly known as AXS-05) for the treatment of agitation associated with Alzheimer disease (AD).^1,2 It is only the second approved medication for AD agitation, and it has a novel mechanism of action.

Auvelity is a first-in-class treatment for AD agitation which targets the N-methyl D-aspartate (NMDA) and sigma-1 receptors. Auvelity works on the NMDA receptor, an ionotropic glutamate receptor, and on the sigma-1 receptor in the brain via its dextromethorphan component. The bupropion component of Auvelity is an aminoketone which increases blood levels of dextromethorphan by inhibiting cytochrome P450 2D6 (CYP2D6), which catalyzes a major biotransformation pathway for dextromethorphan. The exact mechanism of action of Auvelity in the treatment of agitation associated with dementia due to AD is unclear.¹

Psychiatric Times sat down with Rajesh R. Tampi, MD, MS, DFAPA, DFAAGP, our geriatric psychiatry Section Editor, about the impact this drug will have on patients with AD.

Notably, Tampi shared that Auvelity has an entirely different mechanism of action to brexpiprazole (Rexulti), the medication first approved to treat agitation in patients with AD.^3,4

While this approval is very welcome, Tampi also implored psychiatric clinicians to be cautious about prescribing, as this treatment may not work for every patient. “Be thoughtful and do a good assessment. Decide on treatment planning in conjunction with the patient’s family members. Remember, front and center of the treatment of Alzheimer disease and other neurodegenerative diseases, is the patient and their family,” said Tampi.

Dr Tampi is professor and chair of the Department of Psychiatry at Creighton University School of Medicine and Catholic Health Initiatives Health Behavioral Health Services. He is also an adjunct professor of psychiatry at Yale School of Medicine in New Haven, Connecticut, and a member of the Psychiatric Times editorial board.

References

1. Axsome Therapeutics announces FDA approval of Auvelity® (dextromethorphan hbr and bupropion hcl) for the treatment of agitation associated with dementia due to Alzheimer’s disease. News release. April 30, 2026. Accessed April 30, 2026. https://axsometherapeuticsinc.gcs-web.com/news-releases/news-release-details/axsome-therapeutics-announces-fda-approval-auvelityr

2. Kuntz L. FDA approves Auvelity for treatment of agitation in Alzheimer disease. Psychiatric Times. April 30, 2026. https://www.psychiatrictimes.com/view/fda-approves-auvelity-for-treatment-of-agitation-in-alzheimer-disease

3. Lee D, Slomkowski M, Hefting N, et al. Brexpiprazole for the treatment of agitation in Alzheimer dementia: a randomized clinical trial. JAMA Neurol. Published online November 6, 2023.

4. Allen J, Dickan A, Woo J, et al. Exploring the role of brexpiprazole in Alzheimer dementia agitation. Psychiatric Times. 2024;41(1).