Dextromethorphan & Bupropion: Pharmacology, Indications, Dosing Guidelines and Adverse Effects

Dextromethorphan/bupropion is an oral NMDA receptor antagonist combination that produces rapid antidepressant effects within the first week of treatment. Bupropion inhibits CYP2D6, enhancing dextromethorphan's bioavailability. Absolute contraindications include seizure disorders, eating disorders, and abrupt discontinuation of alcohol or benzodiazepines. Dosing adjustments are needed for patients taking strong CYP2D6 inhibitors or those with moderate renal impairment. Clinical use requires assessing abuse potential, managing common adverse effects like dizziness and nausea, and monitoring for severe events such as serotonin syndrome and angle-closure glaucoma.

Study at a glance

Abstract

After completing this activity, participants should be able to: Identify the unique pharmacological mechanism of dextromethorphan/bupropion as an oral NMDA receptor antagonist combination and describe how bupropion's CYP2D6 inhibition enhances dextromethorphan's bioavailability to produce rapid antidepressant effects within the first week of treatment. Recognize absolute contraindications for dextromethorphan/bupropion (including seizure disorders, eating disorders, and abrupt discontinuation of alcohol or benzodiazepines) and apply appropriate dosing adjustments for patients taking strong CYP2D6 inhibitors or those with moderate renal impairment. Evaluate the risk-benefit profile of dextromethorphan/bupropion in clinical practice, including assessment of abuse potential, management of common adverse effects (dizziness, nausea), and monitoring requirements for severe adverse events such as serotonin syndrome and angle-closure glaucoma.