FDA Approves First Non-Antipsychotic for Alzheimer’s Agitation

Written by Ted Samson

Posted on May 18, 2026

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The U.S. Food and Drug Administration (FDA) has approved Auvelity, a combination of dextromethorphan hydrobromide and bupropion hydrochloride, to treat agitation linked to Alzheimer’s dementia in adults.

Auvelity is the first FDA-approved treatment for Alzheimer’s-related agitation that isn’t an antipsychotic. Brexpiprazole (Rexulti), an antipsychotic medication, was FDA-approved for this same condition in May 2023.

This drug combination may give doctors another option when calming routines, better communication, and other nonmedication approaches aren’t enough.

Auvelity was first approved in 2022 to treat major depressive disorder. The new approval means Auvelity can also be used to treat agitation linked to Alzheimer’s disease.

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What Is Agitation in Alzheimer’s Disease?

Agitation is common in people living with Alzheimer’s disease, especially as the condition progresses. Agitation may involve:

Pacing, wandering, or repeated movements
Shouting, arguing, or using angry language
Hitting, pushing, or resisting care

These symptoms can happen for many reasons, including confusion, frustration, pain, changes in environment, poor sleep, or difficulty communicating needs.

Agitation can be one of the most stressful parts of Alzheimer’s disease, often affecting relationships, safety, and quality of life.

What Is Auvelity and How Does It Work?

Auvelity is a prescription tablet that contains two medications: dextromethorphan and bupropion. It is not meant to be taken only when agitation happens.

Researchers don’t yet know exactly how this drug combination helps reduce agitation in people with Alzheimer’s disease. However, the drug seems to affect brain signals involved in mood, behavior, and emotional control.

What Clinical Trials Found

The FDA approval was based on two randomized clinical trials involving adults with Alzheimer’s-related agitation.

In the first study, those who received the drug combination showed an average 14.9-point improvement in their Cohen-Mansfield Agitation Inventory (CMAI) score. Those who received a placebo (inactive treatment) saw an average 11.6-point improvement.

The CMAI is a caregiver-reported questionnaire used to measure how often agitated behaviors happen in older adults.

In the second study, participants who improved while taking the drug combination were randomly assigned to either continue the drug or switch to a placebo. Those who stayed on treatment had a significantly longer time before agitation symptoms returned compared with those who switched to placebo.

Common and Serious Side Effects

Like all treatments, Auvelity can cause side effects.

In clinical trials for agitation linked to Alzheimer’s dementia, the most common side effects were dizziness and dyspepsia, or upset stomach. The FDA also lists other common side effects for Auvelity, including:

Headache
Diarrhea
Drowsiness
Dry mouth
Sexual dysfunction
Uncontrolled sweating

Auvelity has a boxed warning about increased risk of suicidal thoughts and behaviors in adolescents and young adults taking antidepressants.

Serious risks may include:

Seizures
Increased blood pressure or hypertension (high blood pressure)
Mania or hypomania (unusually elevated mood or energy)
Serotonin syndrome (a potentially serious drug reaction)
Dizziness that may increase fall risk
Severe allergic reactions

Why This Approval Matters for Alzheimer’s

Treatment options for agitation in Alzheimer’s have been limited. Doctors usually try nonmedication treatments first. These approaches can include keeping routines calm, improving communication, treating pain, and reducing stress in the person’s surroundings.

However, when symptoms become severe or disruptive, a doctor may recommend medication. The antipsychotic brexpiprazole is FDA-approved for agitation associated with dementia due to Alzheimer’s disease. Other antipsychotic medications may still be used off-label, meaning they’re prescribed for a use that isn’t specifically FDA-approved.

Although these drugs can help some people, antipsychotics have serious safety warnings, including an increased risk of death in older adults with dementia-related psychosis.

The combination of dextromethorphan and bupropion offers an alternative to antipsychotic medications. It also has serious safety warnings.

If you or a loved one living with Alzheimer’s disease is experiencing agitation, talk with a healthcare provider about options that fit your treatment goals.