What Is the New Depression Medication Auvelity?

Summary: The new depression medication Auvelity is a combination of two medications, designed to work together to improve outcomes for people with major depressive disorder (MDD).

Key Points:

• Auvelity was approved by the Food and Drug Administration (FDA) for the treatment of major depressive disorder (MDD) in 2022.
• Auvelity was also FDA-approved for the treatment of agitation in Alzheimer’s dementia in 2026.
• The new formulation of Auvelity includes the medications bupropion and dextromethorphan.
• In Auvelity, the two medications target different brain mechanisms associated with major depressive disorder (MDD) and Alzheimer’s disease.

The Ongoing Effort to Improve Treatment for Depression and Other Mental Health Disorders

While Auvelity made news recently because of its approval for agitation in Alzheimer’s disease, we’ll focus on the use of the new depression medication Auvelity for the treatment of major depressive disorder (MDD).

The symptoms of depression can disrupt daily life and have a negative effect on relationships, work, school, and overall emotional and psychological wellness. In addition, when compared to people without a diagnosis of major depressive disorder (MDD), people diagnosed with MDD show an increased prevalence of chronic physical diseases and conditions, including:

• Cardiovascular conditions, i.e. heart problems, heart failure, hypertension
• Metabolic disorders, including diabetes and some endocrine disorders
• Neurological disorders, including Alzheimer’s disease and Parkinson’s disease
• Muscular and skeletal disorders, including osteoarthritis
• Gastrointestinal disorders, including gastritis, duodenitis
• Some cancer, including breast cancer

Diagnosis of MDD is also associated with increased risk of co-occurring mental health and behavioral disorders, including:

• Anxiety disorders (GAD, SAD, PD, others)
• Bipolar disorders (BD I&II)
• Alcohol and/or substance use disorder (AUD/SUD)
• Eating disorders
• Post-traumatic stress disorder (PTSD)

That’s why it’s important for researchers to keep looking for ways to improve treatment, like with the new depression mediation Auvelity. There are several things we can improve about depression treatment:

1. Not all people with MDD respond to treatment, whether that means psychotherapy or pharmacology (medication)
2. The antidepressive benefits of antidepressant medication can take weeks, or longer, to appear.
3. For some patients, the negative side effects of antidepressants outweigh the symptom relief benefits.

With all that in mind, let’s take a look at how many people in the U.S. have MDD, how many have severe MDD, and how many get treatment for MDD.

Major Depressive Disorder (MDD): Prevalence and Treatment Facts and Figures

The following data is available from a National Institutes of Health (NIH) resource called the 2024 National Survey on Drug Use and Health (2024 NSDUH). This annual survey of over 70,000 people offers insight into the current prevalence of mental health – and other – disorders in any given year. The NSDUH is valuable because the sample size is large enough to draw population-level conclusions, and it breaks data down by age, demographic, and various other categories that help mental health providers and public officials understand where we most need to concentrate our treatment and prevention efforts.

Here’s the latest data on major depressive episodes in the U.S., which is a proxy metric for MDD.

MDE in 2024

21.4 million adults

• Total: 8.2%
• 18-25: 15.9%
• 26-49: 10.0%
• 50+: 4.4%

MDE with Severe Impairment in 2024

14.7 million adults

• Total: 5.6%
• 18-25: 11.5%
• 26-49: 7.0%
• 50+: 2.6%

In this data, severe impairment means the symptoms of MDD prevented the individual from full participation in the activities of daily life, such as school, work, and family responsibilities. In some cases, people with severe impairment associated with MDD may also have problems attending to personal necessities such as hygiene, eating, rest, and basic self-care.

Now let’s look at treatment statistics.

Received Treatment for MDD in 2024 Among People With MDE

Inpatient:

• Total: 4.9%
• 18-25: 5.7%
• 26-49: 5.5%
• 50+: 2.8%

Outpatient:

• Total: 46.4%
• 18-25: 46.2%
• 26-49: 47.0%
• 50+: 45.2%

And finally, the statistics on the prevalence of treatment with prescription medication, i.e., the number people most likely to consider treatment with the new depression medication Auvelity.

Received Prescription Medication for MDD Among People With MDE

• Total: 50.9%
• 18-25: 44.2%
• 26-49: 50.0%
• 50+: 59.5%

Based on a total of 21.4 million people with MDE, those figures mean that roughly 10.5 million people may be likely to consider treatment with a new antidepressant, based on their previous willingness to engage in pharmacologic treatment – i.e. take medication – for MDD.

What’s Different About Auvelity?

Here’s the primary reason a patient might consider Auvelity rather than earlier antidepresssant, as reported in the publication “Rapid-Acting Oral Drug (Auvelity) For Major Depressive Disorder:

“It’s the first and only oral medication with a fast onset of action that has been approved for the treatment of MDD and carries a label indicating statistically significant antidepressant efficacy starting at one week when compared to a placebo.”

That’s a big deal, and potentially significant advantage over medications that take two weeks or longer to achieve a clinically significant antidepressant effect. The rapid effect of this new medication is related to the novel combination of two medications, dextromethorphan and bupropion. We’ll explain how they work, starting with dextromethorphan.

Dextromethorphan for Depression:

You may recognize dextromethorphan as a cough suppressant, and it is. It achieves its cough suppressing effect by acting on brain systems that send signals to the body to cough, with one of the systems also impacting chemicals associated with mood.

Additional details:

• Dextromethorphan an NMDA receptor antagonist.
• NMDA improves neuroplasticity and affects neurons associated with circulating levels of glutamate and serotonin, both of which have a positive impact on mood in people with major depressive disorder.

Bupropion for Depression:

You may recognize bupropion as the active ingredient in the antidepressant Wellbutrin. To learn more about Wellbutrin, please read this article on our blog:

How Does Wellbutrin Help With Depression?

• Bupropion is an atypical antidepressant invented in 1969 and approved by the FDA in 1985
• It’s a norepinephrine-dopamine reuptake inhibitor (NDRI)
• Bupropion blocks a molecule called the norepinephrine transporter (NET) and inhibits the action of a molecule called the dopamine transporter (DAT)
• This action increases the amount of dopamine and norepinephrine in the brain, which is associated with improved mood and decreased depressive symptoms

Additional details:

• Bupropion blocks the action of an enzyme called CYP2D6
• This decreases the speed at body breaks down dextromethorphan, which increases the amount of the medication available in the bloodstream, i.e. its bioavailability.

We’ll discuss these medications further, below.

How This Medication Can Improve Treatment for Our Patients

Experts theorize that the combined, multifaceted action of dextromethorphan and bupropion account for the rapid symptom relief associated with Auvelity. As indicated above, clinical trials comparing combined dextromethorphan and bupropion to placebo alone show improvement in depressive symptoms within one week, with symptom relief lasting for up to 4-6 weeks.

That’s a significant development in antidepressant medication and depression treatment overall. It’s common for antidepressants to take two weeks or longer to relieve symptoms, and patients often wait 6-8 weeks before switching medication or trying a different treatment approach. This new medication has the potential to streamline the treatment process and – in a best case scenario – may offer fast relief and eliminate the need for the time-consuming trial and error period that often accompanies treatment for depression.

Choosing the Right Medication

When we read that a new medication might work more quickly than previous medications, and offer relief for just as long, or longer, than other medications, it begs the question: why would anyone use a different medication?

The answer is that treatment for mental health disorders is an individualized process that involves a combination of psychotherapy, counseling, education, lifestyle changes, social support, and medication when indicated.

In mental health treatment, every medication doesn’t work for everyone, and every psychotherapeutic approach doesn’t work for everyone. Finding the right combination of treatment takes time: therapy and yoga might work for one person, meditation and medication might work for another, and medication and group counseling might work for another.

When antidepressant medication is involved, there are also genetic factors at play, interactions with other medications for other medical conditions involved. While Auvelity may shorten the process of choosing a medication, it may take time to discover the appropriate mix of additional therapies and allow them to work.

Finally, there are side effects to consider:

• Dizziness
• Diarrhea
• Dry mouth
• Sweating
• Drowsiness
• Decreased libido

There are also a number of more serious side effects in specific populations:

• Seizures
• Hypertension
• Manic episodes in people with bipolar disorder
• Psychosis (when taken at higher doses)
• Glaucoma
• Serotonin syndrome

Like all antidepressants in this class, Auvelity carries a black box warning indicating that antidepressants have increased risk of suicidal thoughts and behaviors in children and young adults.

Therefore, while Auvelity is an important development in medication for depression, it’s essential to remember that treatment for mental health disorders involves a wide variety of factors. When choosing a medication and developing a treatment plan, patients and providers consider the options and weigh the risks and benefits of each aspect of treatment, including medication.