The U.S. Food and Drug Administration has approved an expanded use for Auvelity, marking the first non-antipsychotic medication authorized to treat agitation associated with dementia due to Alzheimer’s disease in adults.

The drug, a combination of dextromethorphan hydrobromide and bupropion hydrochloride in extended-release tablet form, was initially approved in 2022 for major depressive disorder. According to a news release, the latest decision provides a new treatment option for one of the most challenging symptoms of Alzheimer’s disease, a condition that affects millions of Americans and places significant strain on patients, families and caregivers.

"This approval represents a significant advancement in our ability to help patients and families dealing with one of the most challenging aspects of Alzheimer's disease," FDA Commissioner Marty Makary, M.D., M.P.H. said in the release. "With today’s action, patients and their families have access to an additional important treatment for complications of this devastating disease."

Agitation is a frequent and often severe symptom in Alzheimer’s patients. It can include excessive movement as well as verbal or physical aggression, and it is widely recognized as a major factor in declining quality of life and increased caregiver burden. Until now, treatment options have been limited, often relying on antipsychotic medications that carry their own risks.

"Auvelity was found to be efficacious for treating agitation in Alzheimer’s disease in two randomized trials and now represents an additional option to address one of the most difficult sequelae of the disease, especially as it progresses,” said Tracy Beth Hoeg, M.D., Ph.D., Acting Director of the FDA’s Center for Drug Evaluation and Research. "We hope this approval will provide meaningful benefit to patients, their families, and caregivers."

The FDA based its decision on results from two clinical trials. The first, a five-week randomized study identified as NCT 03226522, compared Auvelity with a placebo. Researchers measured outcomes using the Cohen-Mansfield Agitation Inventory, a caregiver-reported tool that tracks the frequency of agitated behaviors in elderly patients. Participants receiving Auvelity showed significantly greater improvement than those given a placebo.

A second trial, NCT 04947553, evaluated patients who had already responded to the medication. In this randomized withdrawal study, participants either continued Auvelity or were switched to a placebo. The primary measure was time to relapse. Patients who remained on Auvelity experienced a significantly longer delay before agitation symptoms returned compared with those who stopped treatment.

The medication carries potential risks and side effects. The most common include dizziness, upset stomach, headache, diarrhea, drowsiness, dry mouth, sexual dysfunction and excessive sweating. Auvelity also includes a boxed warning about an increased risk of suicidal thoughts and behaviors in adolescents and young adults taking antidepressants. Health care providers are advised to closely monitor patients for worsening symptoms or emerging suicidal thoughts, particularly during early treatment.

Additional risks include seizures, which are more likely at higher doses, as well as elevated blood pressure, hypertension and the potential to trigger mania or hypomania in susceptible individuals. Before prescribing the drug, clinicians are advised to evaluate blood pressure, review any history of bipolar disorder and assess whether patients are taking other medications containing bupropion or dextromethorphan.

The FDA granted both breakthrough therapy and priority review designations for the expanded use, accelerating its evaluation. Approval was awarded to Axsome Therapeutics, the drug’s manufacturer.