NMDA receptor antagonist / norepinephrine-dopamine reuptake inhibitor (NDRI) combination antidepressant
Dextromethorphan acts as an N-methyl-D-aspartate (NMDA) receptor antagonist and a sigma-1 receptor agonist, modulating glutamatergic and neuroplastic activity. Bupropion is a norepinephrine-dopamine reuptake inhibitor (NDRI) and CYP2D6 inhibitor that increases plasma levels of dextromethorphan, enhancing its central effects.
Major depressive disorder (MDD)
Generalized anxiety disorder (GAD), seasonal affective disorder (SAD), depression associated with Alzheimer’s disease (AD)
Oral tablets (45 mg dextromethorphan / 105 mg bupropion ER)
One tablet p.o. daily for 3 days, then increase to one tablet twice daily
45 mg/105 mg twice daily
Dextromethorphan half-life ~22 hours when co-administered with bupropion; bupropion half-life ~21 hours; metabolized primarily via CYP2D6 and CYP2B6
Dizziness, headache, dry mouth, somnolence, sexual dysfunction, increased blood pressure
Hypertension, mania, seizures, hallucinations, serotonin syndrome (if combined with other serotonergic agents)
Monitor blood pressure, mental status, and for signs of serotonin syndrome or mania in at-risk populations
Increased risk of suicidal thoughts and behaviors in children, adolescents, and young adults with MDD and other psychiatric disorders
Dextromethorphan + bupropion is contraindicated in individuals with seizure disorders or a history of bulimia nervosa or anorexia nervosa due to increased seizure risk associated with the bupropion component. Although clinical data remain limited, the dextromethorphan component may offer potential cognitive benefit in individuals with depression-related cognitive dysfunction. Caution is warranted in patients with Alzheimer’s disease (AD) or other neurodegenerative conditions, as dextromethorphan may cause neuropsychiatric effects, including confusion or hallucinations, particularly in more advanced cognitive impairment.