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FDA approves second-ever treatment for Alzheimer's agitation

FDA approves second-ever treatment for Alzheimer's agitation

New Capabilities

Axsome's Auvelity joins Rexulti in a treatment category that did not exist three years ago

May 4th, 2026: Q1 2026 earnings call scheduled

Overview

Updated May 31

Until May 2023, no drug was approved in the United States to treat the agitation that affects up to three-quarters of people with Alzheimer's disease. Doctors reached for antipsychotics off-label, a class of medicines that carries a black-box warning for increased death risk in older dementia patients. On April 30, 2026, the FDA approved Axsome Therapeutics' Auvelity for the indication, doubling approved options from one to two. The FDA called it the 'first non-antipsychotic drug to treat agitation associated with dementia' — what sets it apart from Rexulti.

Auvelity is an oral pill combining dextromethorphan, the cough-suppressant ingredient, with bupropion, an older antidepressant that slows dextromethorphan's breakdown so it can act on the brain. In two pivotal trials, patients on Auvelity relapsed into agitation at 8.4 percent versus 28.6 percent on placebo. Axsome had doubled its salesforce to 600 in the months before approval and activated its Auvelity OnMySide patient support program on approval day, offering savings cards and prior authorization assistance for commercially insured patients. AXSM shares surged, and the company is scheduled to report Q1 2026 financial results on May 4 — its first quarterly disclosure following the new indication.

Why it matters

If a parent develops Alzheimer's agitation, the doctor now has two approved treatments to try—up from zero in 2022.

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Key Indicators

2nd
FDA-approved treatment for Alzheimer's agitation
Joins brexpiprazole (Rexulti), approved in May 2023 as the first ever.
~76%
of Alzheimer's patients experience agitation
Symptoms range from restlessness and pacing to aggression and shouting.
8.4% vs 28.6%
relapse rate on Auvelity vs placebo
ACCORD-2 randomized withdrawal trial measured time to agitation relapse.
~7M
Americans living with Alzheimer's
Population that defines the addressable patient pool for the new indication.
0
approved treatments before May 2023
Off-label antipsychotics carried a black-box warning for increased death risk.

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People Involved

Herriot Tabuteau
Herriot Tabuteau
Chief Executive Officer, Axsome Therapeutics
Leading commercial launch of second Auvelity indication
 George Grossberg
George Grossberg
Professor and Director, Division of Geriatric Psychiatry, Saint Louis University School of Medicine
Provided clinical endorsement at Auvelity approval

Organizations Involved

Axsome Therapeutics
Axsome Therapeutics
Biopharmaceutical company
Commercial launch underway; 600-rep salesforce and OnMySide patient support program activated on day of approval

A New York-based biotech focused on central nervous system disorders, built around reformulating known compounds for new indications.
U.S. Food and Drug Administration
U.S. Food and Drug Administration
Federal regulatory agency
Issued approval on PDUFA action date

The federal agency that reviews and approves prescription drugs in the United States.
OL
Otsuka & Lundbeck
Pharmaceutical co-developers
Maker of incumbent treatment Rexulti

The pharmaceutical partners that brought brexpiprazole (Rexulti)—the first FDA-approved Alzheimer's agitation treatment—to market in 2023.

Timeline

April 2005 May 2026

9 events Latest: May 4th, 2026 · 4 months ago
Tap a bar to jump to that date

  1. Q1 2026 earnings call scheduled

    Latest Corporate

    Axsome is set to report first-quarter 2026 financial results before U.S. markets open — the first quarterly report to include management commentary on Alzheimer's agitation launch momentum.

  2. Axsome holds post-approval investor webcast

    Corporate

    Axsome hosted a conference call at 8:00 a.m. ET to discuss the FDA approval, immediate commercial launch infrastructure, and the Auvelity OnMySide patient support program.

  3. FDA approves Auvelity for Alzheimer's agitation

    Approval

    On the assigned action date, the FDA clears Auvelity as the second-ever approved treatment for agitation associated with dementia due to Alzheimer's disease.

  4. Axsome submits supplemental New Drug Application

    Regulatory

    Company files for the Alzheimer's agitation indication; FDA accepts the submission and assigns a 2026 action date.

  5. ACCORD-2 relapse-prevention trial reports

    Clinical Trial

    Patients stabilized on Auvelity relapsed at 8.4 percent versus 28.6 percent on placebo, providing the relapse-prevention evidence the FDA reviewed.

  6. ADVANCE-1 Phase 3 results published

    Clinical Trial

    Axsome reports that Auvelity significantly reduced agitation versus placebo in patients with Alzheimer's, supporting the regulatory filing.

  7. Rexulti becomes first-ever Alzheimer's agitation treatment

    Approval

    FDA approves brexpiprazole for agitation associated with dementia due to Alzheimer's disease, ending decades without an approved option.

  8. Auvelity wins first FDA approval, for depression

    Approval

    FDA clears Axsome's dextromethorphan-bupropion combination for major depressive disorder, establishing the safety and pharmacology base for later indications.

  9. FDA black-box warning shapes off-label landscape

    Regulatory

    The FDA warns that atypical antipsychotics increase mortality in elderly dementia patients, leaving clinicians with no approved option and a dangerous off-label one.

Historical Context

3 moments from history that rhyme with this story — and how they unfolded.

April 2005

FDA black-box warning on antipsychotics for dementia (2005)

The FDA required a black-box warning on atypical antipsychotics—including risperidone, olanzapine, and quetiapine—after pooled trial data showed elderly patients with dementia-related psychosis faced roughly 1.6 to 1.7 times the mortality risk of those on placebo. The warning was extended to all antipsychotics in 2008.

Then

Off-label prescribing dropped initially but rebounded because clinicians had no approved alternatives for severe agitation.

Now

The warning created a durable regulatory and ethical incentive to develop dementia-specific drugs without antipsychotic mechanisms—the gap Auvelity now partially fills.

Why this matters now

Auvelity's value is defined by what it is not: an antipsychotic. The black-box warning is the policy backdrop that makes a non-antipsychotic mechanism commercially and clinically meaningful.

June 2021 to early 2024

Aduhelm conditional approval and rollback (2021–2024)

The FDA granted accelerated approval to Biogen's Aduhelm for Alzheimer's disease over the objections of its own advisory committee, citing reductions in amyloid plaques rather than clear cognitive benefit. Medicare restricted coverage, sales collapsed, and Biogen discontinued the drug in early 2024.

Then

The approval triggered congressional investigations and damaged trust in the FDA's accelerated approval pathway.

Now

Subsequent Alzheimer's-related approvals have faced sharper scrutiny on trial design and clinical meaningfulness, raising the evidentiary bar that Auvelity's program had to clear.

Why this matters now

Auvelity entered FDA review in the post-Aduhelm environment, where dementia drug approvals attract heightened scrutiny. Its replicated, placebo-controlled trial package reflects what the agency now requires to act in this space.

May 2023

Rexulti approved as first Alzheimer's agitation treatment (2023)

After more than a decade of failed trials by multiple sponsors, the FDA approved Otsuka and Lundbeck's brexpiprazole for agitation in dementia due to Alzheimer's disease. Two pivotal trials showed modest but statistically significant reductions in agitation scores versus placebo.

Then

The approval established the first FDA-cleared option in a category where doctors had relied on off-label antipsychotics carrying mortality warnings.

Now

It validated the regulatory pathway for dementia-symptom drugs and incentivized other sponsors—including Axsome—to push their own programs to filing.

Why this matters now

Rexulti's approval created the category that Auvelity now expands. Without that 2023 precedent, the regulatory and reimbursement frameworks Auvelity steps into would not exist.

Sources

(11)
+5
NeurologyLive Psychiatric Times StockTitan BioWorld U.S. Food and Drug Administration Investing.com BioSpace Healio Pharmacy Times StockTitan / GlobeNewswire Psychiatric Times