Meet the newest antidepressant: Auvelity

The U.S. Food and Drug Administration on August 19, 2022 approved dextromethorphan-bupropion, or Auvelity, a drug used to treat major depressive disorder, also known as clinical depression, in adults.

It is the first drug to treat major depressive disorder that works within a week of taking it and is the first new pill to treat depression using a new mechanism of action in more than 60 years, according to the manufacturer, Axsome Therapeutics.

What’s Different About This Depression Drug

There has long been a need for better and more effective drugs to treat depression, as nearly two-thirds of all people diagnosed with depression do not find relief from them, according to Axsome Therapeutics.

In a double-blind phase 3 clinical trial, 163 patients taking Auvelity said their feelings of depression were significantly improved within a week of beginning the drug, as opposed to 164 patients who took a placebo, according to research published in the Journal of Clinical Psychiatry in May 2022. The drug is as an N-methyl D-aspartate (NMDA) receptor antagonist.

In another randomized double-blind multicenter study of 97 patients with major depression, published in the American Journal of Psychiatry in May 2022, patients who took the combination of dextromethorphan-bupropion, as compared with those who took doses of sustained-release buproprion, reported that their depression symptoms were “significantly reduced” on the Auvelity medication. Current depression medications typically need to be taken consistently for about six weeks before patients report feeling better, the company said.

The main advantage demonstrated in the clinical trials is faster onset of action. Auvelity demonstrated improvement in depression rating scale scores compared to placebo at one week of treatment. Usually, it takes several weeks to show a response with current antidepressant treatments. The only other depression treatment shown to act as quickly as Auvelity is ketamine.

How does Auvelity work?

Auvelity has two active ingredients, so it works in a few ways.

Dextromethorphan affects two types of receptors (chemical binding sites) in your brain. It blocks receptors called N-methyl-D-aspartate (NMDA) receptors, but it activates sigma-1 receptors. This helps glutamate and monoamine chemical messengers become more active and available in your brain. It’s thought that this helps contribute to positive changes in mood.

Bupropion helps support dextromethorphan’s efforts. It gets in the way of an enzyme (protein) that breaks down dextromethorphan. By doing this, dextromethorphan lasts longer in your body. This helps make it more effective. Bupropion may also affect chemical messengers like norepinephrine and dopamine.

By comparison, antidepressants like SSRIs affect serotonin.

Dosage and Protocol

During your first 3 days of taking Auvelity, you’ll likely take one tablet by mouth daily. This helps your body get used to the medication. From that point on, it’s recommended to take one tablet by mouth 2 times daily, at least 8 hours apart. You can take your doses with or without food, but you shouldn’t split, crush, or chew the tablets. Each tablet contains 45 mg of dextromethorphan and 105 mg of bupropion.

Common Side Effects

All medications can cause side effects, including Auvelity. These side effects happened to more than 5% of people in Auvelity’s clinical trials:

·         Dizziness

·         Nausea

·         Headache

·         Drowsiness

·         Diarrhea

·         Dry mouth

·         Sexual dysfunction, including erectile dysfunction, orgasm changes, and a lower sex drive

·         More sweating than usual


Like other antidepressants, Auvelity has a number of drug interactions to keep in mind. If you take any of these medications with Auvelity, your healthcare provider and pharmacist may want to adjust your medication doses and/or warn you about an increased risk of side effects:

·         Monoamine oxidase inhibitors (MAOIs), like selegiline (Zelapar, Emsam) or phenelzine (Nardil)

·         Medications that affect serotonin levels, such as triptan migraine medications and many antidepressants

·         Medications that worsen the risk for seizures, like tramadol (Ultram, ConZip)

·         Medications that make Auvelity last longer in your body, like fluoxetine, paroxetine (Paxil), or mirabegron (Myrbetriq)

·         Medications that make Auvelity less effective, like phenobarbital

·         Medications that raise dopamine levels in your body, like carbidopa/levodopa (Sinemet)

·         Digoxin

·         Alcohol

This isn’t a complete list of possible interactions. To help prevent Auvelity interactions, make sure your healthcare provider and pharmacist have an updated list of medications and supplements that you take.


·         Store at room temperature between 68°F to 77°F (20°C to 25°C).

·         Keep all medicines out of the reach of children and pets.


Given that Auvelity is quite affordable, it makes it accessible to patients from different socio-economic backgrounds. This means that those who need the medication but cannot afford it no longer have to choose between affordability and mental health. The medication is available at most drug stores, and there are various generic brands that are just as effective.

The introduction of Auvelity has been a game-changer in the fight against depression. It provides a medication option that is not only effective but also has few side effects. Patients who have tried other antidepressants without success can opt for Auvelity to see if it works for them. Auvelity is an excellent alternative for individuals struggling with the overwhelming symptoms of depression, especially those that cannot afford the high costs of other antidepressants.

In conclusion, Auvelity is an essential addition to antidepressants, and it has many benefits. It offers fast results, is affordable, effective, and has minimal side effects. Patients should talk to their healthcare providers about the advantages and disadvantages of this medication to help determine if it is the right choice for them. With optimistic research outcomes, it is hopeful that the medication will help many individuals who experience depression.


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