Only about half of people with major depressive disorder respond to their first antidepressant, and around 30% do not achieve remission despite multiple treatments. For those who fail several first-line agents, options include switching to older or non-generic antidepressants, augmenting with antipsychotics, or using electroconvulsive therapy, transcranial magnetic stimulation, or esketamine. Non-generic antidepressants can be costly and require prior authorization. A new combination therapy, dextromethorphan/bupropion, has shown early promise, with efficacy seen as early as week one, but cost and insurance limits may lead to using its components separately. This case report describes a 31-year-old man with treatment-resistant depression and alcohol use disorder whose symptoms improved on bupropion and dextromethorphan, offering observations for managing such cases.
Adding dextromethorphan (DXM) to an antidepressant that inhibits CYP2D6 did not speed improvement of depressive symptoms in adults hospitalized for depression. In a retrospective chart review of 40 patients, median time to clinical improvement was 3.00 days for those receiving DXM plus an antidepressant versus 2.83 days for those receiving only an antidepressant, a difference that was not statistically significant. Perceptual disturbances and delusions occurred more often in the DXM group (55% and 35%) than in the control group (30% and 25%). The authors suggest the commonly used 30 mg daily dose may have been too low, and bupropion, the most frequently used antidepressant, has weaker CYP2D6 inhibition than fluoxetine or paroxetine.