Auvelity: Difference between revisions
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| intro = '''Auvelity''' is a fixed-dose combination of dextromethorphan 45 mg and bupropion 105 mg, FDA-approved August 2022 for major depressive disorder. The combination addresses dextromethorphan's rapid first-pass CYP2D6 metabolism by exploiting bupropion's CYP2D6 inhibition | | intro = '''Auvelity''' is a fixed-dose combination of dextromethorphan 45 mg and bupropion 105 mg, FDA-approved August 2022 for major depressive disorder. The combination addresses dextromethorphan's rapid first-pass CYP2D6 metabolism by exploiting bupropion's CYP2D6 inhibition, without bupropion, oral dextromethorphan never reaches plasma levels sufficient for NMDA antagonism. The rationale builds on ketamine's antidepressant effect: low-dose NMDA antagonism may produce rapid antidepressant response through downstream AMPA/BDNF/synaptogenesis pathways rather than monoamine modulation. Significant antidepressant separation from placebo by week 1 in trials. | ||
| pharmacodynamics= '''Dextromethorphan:''' Uncompetitive NMDA receptor antagonist (binds open channel like ketamine/memantine), sigma-1 receptor agonist, modest SERT and NET inhibition. '''Bupropion:''' Norepinephrine-dopamine reuptake inhibitor (NDRI) plus potent CYP2D6 inhibition (blocking dextromethorphan's metabolism to dextrorphan). | | pharmacodynamics= '''Dextromethorphan:''' Uncompetitive NMDA receptor antagonist (binds open channel like ketamine/memantine), sigma-1 receptor agonist, modest SERT and NET inhibition. '''Bupropion:''' Norepinephrine-dopamine reuptake inhibitor (NDRI) plus potent CYP2D6 inhibition (blocking dextromethorphan's metabolism to dextrorphan). | ||
| effects = Dizziness, headache, diarrhea, somnolence, dry mouth, sexual dysfunction. Lower seizure risk than higher-dose bupropion alone. Avoid in patients with seizure disorders or eating disorders (bupropion contraindication). Avoid with MAOIs (serotonin syndrome / hypertensive crisis risk). | | effects = Dizziness, headache, diarrhea, somnolence, dry mouth, sexual dysfunction. Lower seizure risk than higher-dose bupropion alone. Avoid in patients with seizure disorders or eating disorders (bupropion contraindication). Avoid with MAOIs (serotonin syndrome / hypertensive crisis risk). | ||