FDA Approves Auvelity for Treatment of Agitation Associated with Dementia Due to Alzheimers
Key Takeaways
- FDA cleared the first agent with an NMDA/sigma-1–based mechanism specifically for agitation in Alzheimer’s disease dementia, a symptom complex reported in up to 76% of patients.
- Mechanistic rationale combines dextromethorphan receptor pharmacology with bupropion-mediated inhibition of dextromethorphan breakdown to raise systemic exposure and achieve therapeutic concentrations.
FDA approves Auvelity for Alzheimer’s-related agitation, marking the first therapy targeting NMDA and sigma-1 receptors for this high-burden neuropsychiatric symptom and expanding treatment options for millions of patients.
FDA approved Auvelity (dextromethorphan HBr and bupropion HCl) for the treatment of agitation associated with dementia due to Alzheimer's disease.
The agency’s decision marks the first approval of a drug with this specific mechanism of action for one of the most burdensome and clinically challenging symptoms of the disease.
Jeffrey Cummings, MD, ScD, Chambers-Grundy Professor of Brain Sciences at UNLV, said: "Treatment for agitation associated with Alzheimer's disease dementia has been a critical unmet medical need. The approval of Auvelity for this condition has the potential to play an important role in patient care for this challenging and impactful symptom of Alzheimer's disease."
What is Auvelity?
Auvelity is a first-in-class treatment for Alzheimer's disease agitation that targets the NMDA and sigma-1 receptors in the brain through its dextromethorphan component.1 The bupropion component increases blood levels of dextromethorphan by inhibiting its metabolic breakdown, allowing therapeutic concentrations to be reached. The drug is already FDA-approved for major depressive disorder, an indication also developed with Breakthrough Therapy designation and Priority Review, and has been administered to more than 300,000 patients across clinical and real-world settings.2 The FDA previously granted Breakthrough Therapy designation for this new Alzheimer's agitation indication as well.
Why does Auvelity’s approval matter?
Alzheimer's disease affects more than 7 million Americans and is the most common form of dementia. Agitation is reported in up to 76% of patients and encompasses symptoms ranging from pacing and restlessness to verbal and physical aggression. It is among the most persistent, costly, and distressing aspects of care for patients, families, and caregivers, and is associated with accelerated cognitive decline, placement in residential care facilities, and increased mortality risk.
"The approval of our first-in-class medication for agitation associated with Alzheimer's disease marks an important milestone for the millions of patients living with Alzheimer's disease, their families, and their caregivers," said Herriot Tabuteau, MD, CEO of Axsome. "Alzheimer's disease agitation is the second neuropsychiatric indication for which Auvelity has received FDA Breakthrough Therapy designation, and been granted FDA Priority Review and approval, underscoring Axsome's pioneering work in neuroscience and our dedication to people living with serious brain health conditions."
What is the approval based on?
The approval is supported by two Phase III studies. Advance-1 was a five-week, double-blind, randomized trial in which Auvelity demonstrated statistically significant superiority over placebo in reducing agitation symptoms as measured by the Cohen-Mansfield Agitation Inventory at week five.1
A significantly greater proportion of Auvelity -treated patients were rated as at least minimally improved by clinicians on a key secondary endpoint. Only 1.3% of patients discontinued due to adverse events, the same rate as placebo, with dizziness and dyspepsia the most common adverse reactions.1
Accord-2 was a long-term randomized withdrawal trial in which known Auvelity responders were re-randomized to continue treatment or switch to placebo for up to six months. Patients who continued on Auvelity experienced a statistically significantly longer time to relapse of agitation symptoms compared to those switched to placebo.1
George Grossberg, MD, professor and director of the Division of Geriatric Psychiatry at Saint Louis University School of Medicine, said: "Auvelity is the only FDA-approved product to result in a statistically significantly longer time to relapse of agitation symptoms, compared to placebo, in a long-term study. Importantly, Auvelity showed a compelling safety and tolerability profile, with rates of discontinuation due to adverse events that were low and matched those of placebo."
Sources
- 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 Axsome Therapeutics April 30, 2026
https://axsometherapeuticsinc.gcs-web.com/news-releases/news-release-details/axsome-therapeutics-announces-fda-approval-auvelityr - Axsome Therapeutics Announces FDA Approval of Auvelity, the First and Only Oral NMDA Receptor Antagonist for the Treatment of Major Depressive Disorder in Adults Axsome Therapeutics August 19, 2022
https://axsometherapeuticsinc.gcs-web.com/node/10466/pdf
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