FDA expands Auvelity use for Alzheimer’s agitation, first non-antipsychotic option

Alzheimer’s agitation can upend a household, turning restlessness, emotional distress and verbal or physical aggression into a daily caregiving emergency. The Food and Drug Administration’s expansion of Auvelity on April 30 gave doctors the first FDA-approved treatment for agitation linked to dementia due to Alzheimer’s disease that is not an antipsychotic, a shift with clear implications for safety, caregiver burden and the limits of current dementia care.

Auvelity was first approved in 2022 for major depressive disorder in adults. For the new indication, the FDA said its decision rested on randomized clinical trials, including a five-week placebo-controlled study that measured change from baseline to week five on the Cohen-Mansfield Agitation Inventory and a randomized-withdrawal relapse study. In the withdrawal trial, patients who stayed on Auvelity remained free of relapse longer than those switched to placebo. The agency said the drug’s most common side effects included dizziness, upset stomach, headache, diarrhea, drowsiness, dry mouth, sexual dysfunction and sweating. It also noted the boxed warning on suicidal thoughts and behaviors in adolescents and young adults that applies to antidepressants.

FDA Commissioner Marty Makary called the decision a “significant advancement” for patients and families struggling with Alzheimer’s agitation. Tracy Beth Hoeg, acting director of the FDA’s Center for Drug Evaluation and Research, said the medication gives clinicians an additional option for one of the disease’s most difficult sequelae. That matters because agitation is not a minor behavioral issue. It can trigger injuries, emergency visits, caregiver burnout and eventual institutionalization, especially when symptoms become hard to manage at home or in long-term care.

The Alzheimer’s Association welcomed the approval and said agitation can include restlessness, emotional distress and physical or verbal aggression. Joanne Pike said people with Alzheimer’s agitation and their families have had limited options and that existing options carried significant risks. The group said non-pharmacological strategies, including environmental modifications, structured routines and psychosocial interventions, remain first-line treatment for behavioral and psychological symptoms of dementia. Auvelity offers another tool when those measures are not enough.

Axsome Therapeutics said the drug targets NMDA and sigma-1 receptors and that the approval was supported by the Phase 3 ADVANCE-1 and ACCORD-2 studies. The company also said Auvelity had received Breakthrough Therapy designation and Priority Review for this indication. Axsome said Alzheimer’s disease affects more than 7 million Americans and that agitation is reported in up to 76% of patients. The approval arrives after Rexulti, or brexpiprazole, won FDA clearance in May 2023 as the first treatment for Alzheimer’s agitation, but Auvelity now stands apart as the first non-antipsychotic option. That leaves unanswered questions about cost, access and how well the drug will perform outside clinical trials, even as it broadens the medical response to one of dementia’s most disruptive symptoms.