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Clinical Overview: Auvelity (Dextromethorphan and Bupropion) for Major Depressive Disorder

Clinical Overview: Auvelity (Dextromethorphan and Bupropion) for Major Depressive Disorder

Major depressive disorder (MDD) is diagnosed using the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5) criteria, which includes symptoms such as depressed mood, loss of interest or pleasure, weight loss or gain, insomnia or hypersomnia, agitation, fatigue, feelings of worthlessness, decreased concentration, and thoughts of death or suicide.

With an abundance of medications and different classes of medications used in the treatment of MDD, pharmacists play a major role and can have a large impact on patients’ lives, from counseling on medications to assisting physicians and patients with finding the right medication. Because pharmacists are the medication experts, it is important that we are educated about the new depression medication, dextromethorphan and bupropion (Auvelity), so we are comfortable with counseling and recommending this medication to treat our patient's depression.


In August 2022, Axsome Therapeutics achieved FDA approval for the first of its kind antidepressant sold under the brand name of Auvelity, which is a combination of the FDA-approved medications dextromethorphan and bupropion. Auvelity is indicated for the treatment of MDD in adults.

Mechanism of Action

This new antidepressant has a unique mechanism of action and is the only rapid-acting oral treatment for MDD. Dextromethorphan is an uncompetitive N-methyl-d-aspart (NMDA) receptor antagonist, which increases glutamate.

Dextromethorphan is also an agonist at the sigma-1 receptor, which increases serotonin levels. Bupropion blocks reuptake of norepinephrine and dopamine, which increases availability. It also acts as an inhibitor of CYP2D6, which then increases the concentration of dextromethorphan.

Dosing and Administration

Auvelity is an extended-release tablet containing 45 mg of dextromethorphan hydrobromide and 105 mg of bupropion hydrochloride.


The efficacy was based on the GEMINI phase 3, randomized, placebo-controlled clinical trial.

November 8, 2022


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