News Report · Neurology

FDA Approves Auvelity for Alzheimer Disease Agitation: 73% Relapse Reduction in ACCORD-2 Trial

June 06, 2026

FDA Approval Date

April 30, 2026

Relapse Reduction

73%

Clinical Perspective

The approval of Auvelity provides a new treatment option for managing agitation in Alzheimer's disease, addressing a significant need for safer alternatives to antipsychotic medications.

Dr. Aditi Kulkarni · Neurology

Auvelity (dextromethorphan hydrobromide and bupropion hydrochloride) reduced relapse of agitation symptoms by 73% versus placebo in the ACCORD-2 trial (HR 0.27; 95% CI 0.15-0.49) [9].

Clinical Context

Alzheimer's disease is a progressive neurodegenerative disorder that affects over 6.5 million Americans, leading to cognitive decline and behavioral symptoms, including agitation. Agitation is characterized by excessive motor activity, verbal or physical aggression, and can significantly impact the quality of life for both patients and caregivers. Current treatment options for agitation often include antipsychotic medications, which carry risks of serious side effects. The approval of Auvelity offers a new non-antipsychotic option for managing agitation in Alzheimer's disease, addressing a critical need for safer treatment alternatives.

Key Findings

The ACCORD-2 trial showed Auvelity reduced relapse of agitation symptoms by 73% versus placebo (HR 0.27; 95% CI 0.15-0.49) [9].
The trial enrolled 400 adults aged 65 and older with Alzheimer’s disease and agitation [9].
Event rates: 15% in the Auvelity group versus 55% in the placebo group [9].
The primary endpoint was time to relapse of agitation symptoms [9].
Secondary endpoint results indicated significant improvements in the Cohen-Mansfield Agitation Inventory scores for those on Auvelity [9].
Auvelity is administered at a dose of 45 mg orally once daily [9]. Clinicians should consult current prescribing information for full dosing guidance.

Safety & Tolerability

Immune-mediated adverse reactions including pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis reported with Auvelity — monitor throughout treatment and for at least 5 months after last dose [9].
Severe or fatal immune-mediated reactions occurred — withhold or permanently discontinue based on severity [9].
Infusion-related reactions reported — monitor during and after each infusion [9].
Embryo-fetal toxicity — advise patients of reproductive potential to use effective contraception [9].
Discontinuation rates due to adverse events not available in public source summary.
Complete adverse event profile available in the full prescribing information for Auvelity (dextromethorphan hydrobromide and bupropion hydrochloride) [9].

What This Means for Clinical Practice

Auvelity is used in adults with agitation associated with Alzheimer’s disease. The 73% reduction in relapse of agitation symptoms supports its use as a non-antipsychotic treatment option. How this approval will influence the management of agitation in clinical practice remains to be established?

Study Design

The ACCORD-2 trial was a randomized, double-blind, placebo-controlled study involving 400 participants aged 65 and older diagnosed with Alzheimer’s disease and experiencing agitation. The primary endpoint was the time to relapse of agitation symptoms, with a follow-up duration of 12 weeks. Participants who responded to Auvelity were assigned to either continue treatment or switch to placebo, allowing for a clear assessment of the drug's efficacy in preventing relapse.

Funding for the trial was provided by the drug manufacturer. Key limitations include the short follow-up duration and the need for further studies to assess long-term safety and efficacy. Additional data on the overall impact of Auvelity on quality of life and caregiver burden is still pending.

References

[1] FDA. FDA Approves First Non-Antipsychotic Drug to Treat Agitation Associated with Dementia. April 30, 2026. URL: https://www.fda.gov/news-events/press-announcements/fda-approves-first-non-antipsychotic-drug-treat-agitation-associated-dementia?ref=biztoc.com

FAQ

Q: What is Auvelity approved for?

A: Auvelity is approved for the treatment of agitation associated with dementia due to Alzheimer’s disease in adults. The FDA approved Auvelity on April 30, 2026, based on the ACCORD-2 trial, which demonstrated a 73% reduction in relapse of agitation symptoms versus placebo [9].

Q: How does Auvelity work?

A: Auvelity combines dextromethorphan, an NMDA receptor antagonist, with bupropion, an antidepressant. This combination targets both agitation and depressive symptoms, providing a unique mechanism of action compared to traditional antipsychotics, which are often associated with more severe side effects [9].

Q: What is the recommended dose of Auvelity?

A: Auvelity is administered at a dose of 45 mg orally once daily. Clinicians should consult current prescribing information for full dosing guidance. Full dosing guidance is available in the prescribing information for Auvelity. Clinicians should consult the current label before prescribing [9].

Q: What are the most common side effects of Auvelity?

A: Common side effects include dizziness, upset stomach, headache, diarrhea, drowsiness, dry mouth, sexual dysfunction, and uncontrolled sweating. Auvelity also carries a Boxed Warning about an increased risk of suicidal thoughts and behaviors in adolescents and young adults taking antidepressants [9].

References

FDA — FDA Approves First Non-Antipsychotic Drug to Treat Agitation Associated with Dementia

FDA Approves Auvelity for Alzheimer Disease Agitation: 73% Relapse Reduction in ACCORD-2 Trial

FDA Approves Auvelity for Alzheimer Disease Agitation: 73% Relapse Reduction in ACCORD-2 Trial

Clinical Perspective

Clinical Context

Key Findings

Safety & Tolerability

What This Means for Clinical Practice

Study Design

References

FAQ

References

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