Daily Medication Pearl: Dextromethorphan and Bupropion (Auvelity)

Auvelity is a combination of dextromethorphan and bupropion indicated for the treatment of major depressive disorder in adults.

Pearl of the day medication: Dextromethorphan and Bupropion (Auvelity)

Indication: Auvelity is a combination of dextromethorphan, a non-competitive N-methyl D-aspartate (NDMA) receptor antagonist and sigma-1 receptor agonist, and bupropion, an aminoketone and CYP450 2D6 inhibitor, indicated for the treatment of depressive disorder major (CT) in adults.


  • Dosage: The starting dose is 1 tablet once a day in the morning. After 3 days, increase to the maximum recommended dose of 1 tablet twice a day, spaced at least 8 hours apart. Do not exceed 2 doses in the same day.
  • Dosage forms: Prolonged-release tablets 45 mg/105 mg dextromethorphan/bupropion.
  • Adverse events: The most common adverse reactions (≥5% and more than twice as common as placebo) are dizziness, headache, diarrhea, somnolence, dry mouth, sexual dysfunction, and hyperhidrosis.
  • Action mechanism: Dextromethorphan is a non-competitive antagonist of the NMDA receptor (an ionotropic glutamate receptor) and an agonist of the sigma-1 receptor. The mechanism of dextromethorphan in the treatment of MDD is unclear. The mechanism of action of bupropion in the treatment of MDD is unclear; however, it may be related to noradrenergic and/or dopaminergic mechanisms. Bupropion increases plasma dextromethorphan levels by competitively inhibiting cytochrome P450 2D6, which catalyzes a major dextromethorphan biotransformation pathway. Bupropion is a relatively weak inhibitor of neuronal norepinephrine and dopamine reuptake and does not inhibit monoamine oxidase or serotonin reuptake.

Reference: prescribing-information-auvelity.pdf (axsome.com)

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