FDA
FDA clears Auvelity as first non‑antipsychotic for agitation in Alzheimer’s dementia
On April 30, 2026, FDA approved Auvelity (dextromethorphan/bupropion hydrochloride extended‑release) for the treatment of agitation associated with dementia due to Alzheimer’s disease in adults. The oral therapy is the first non‑antipsychotic approved for this indication and targets NMDA and sigma‑1 receptors, offering a differentiated approach for a long‑standing unmet need.
Approval was supported by a phase 3 program including ADVANCE‑1 and ACCORD‑2. In ADVANCE‑1, a 5‑week randomized, double‑blind trial, Auvelity produced statistically significant improvement in agitation vs. placebo on the Cohen‑Mansfield Agitation Inventory (CMAI) at week 5, with more patients rated at least minimally improved on a clinician‑reported global change scale. In the long‑term ACCORD‑2 randomized withdrawal study (up to 6 months), patients who continued Auvelity had a significantly longer time to relapse of agitation symptoms than those switched to placebo.
Across short‑ and long‑term studies, Auvelity showed a generally favorable tolerability profile. The most common adverse events in agitation trials were dizziness and dyspepsia, and discontinuation due to adverse events was low (1.3%), matching placebo.
“Agitation is highly prevalent in patients with Alzheimer’s disease and among the most burdensome aspects of the disease for patients and families," said Jeffrey Cummings, MD, ScD, Chambers-Grundy Professor of Brain Sciences, UNLV Kirk Kerkorian School of Medicine. "Alzheimer’s disease agitation is associated with accelerated cognitive decline, placement in assisted living and long-term care facilities, and increased mortality risk. 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."
Sources:
Axsome Therapeutics. (2026, April 30). Press release. 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
U.S. Food and Drug Administration. (2026, April 30). News release. FDA Approves First Non-Antipsychotic Drug to Treat Agitation Associated with Dementia