The first N-methyl D-aspartate (NMDA) receptor antagonist for the treatment of major depressive disorder (MDD) in adults has been accorded FDA approval. It is a combination of dextromethorphan, an uncompetitive NMDA receptor antagonist and sigma-1 receptor agonist with bupropion, which is an aminoketone and CYP450 2D6 inhibitor. The drug is not approved for use in children. In trials, the efficacy has been seen as early as one week. The drug is expected to be launched in the later part of this year.

Formulation: Oral extended-release tablet in the strength of dextromethorphan hydrobromide (45 mg) and bupropion hydrochloride (105 mg).

Dose and administration: One tablet once daily in the morning x 3 days (starting dose); increase to one tablet twice daily (maximum dose). In patients with moderate renal impairment or persons who are CYP2D6 poor metabolizers, the dose is one tablet orally once daily in the morning.

Contraindications: Known hypersensitivity to bupropion, dextromethorphan or other components, seizure disorders, diagnosed bulimia or anorexia nervosa, suddenly stopping alcohol, benzodiazepines, barbiturates and antiepileptic drugs, pregnant and lactating women, severe hepatic and renal impairment.

Side effects: Headache, diarrhea, dizziness, somnolence, dry mouth, hyperhidrosis, sexual dysfunction.

Warnings and precautions

• Before initiating treatment, evaluate the patient for high blood pressure and enquire about history of bipolar disorder, mania or hypomania.
• Be on the lookout for seizures, the risk of which is dose-related. Stop the drug if seizure occurs.
• Monitor the blood pressure of the patient as the drug may cause hypertension.
• Psychosis/other neuropsychiatric reactions, including closed angle glaucoma may occur.
• Avoid within 2 weeks of discontinuing a monoamine oxidase inhibitor (MAOI).
• Potential embryo-fetal toxicity.

Sources

1. AUVELITY prescribing information, FDA https://www.auvelity.com/prescribing-information.pdf
2. FDA approves rapid-acting oral drug for major depression - Medscape - Aug 22, 2022.