Playing with a full dex of cards: Treatment resistant depression with suicidality responds to inpatient dextromethorphan therapy

Treatment resistance is common in major depressive disorder (MDD), prompting the development of new and novel therapies. While historically many antidepressants have targeted monoamine pathways, recently there has been increased interest in glutamatergic therapies, most prominently ketamine and esketamine, which more rapidly induce remission of depressive symptoms. Dextromethorphan (DXM), an FDA approved antitussive medication, exhibits similar subjective effects and pharmacodynamics to ketamine, in particular N-methyl-D-aspartate (NMDA) receptor antagonism, and a combination treatment of DXM with bupropion (BUP), which inhibits CYP2D6 and increases the bioavailability and half-life of DXM, has shown efficacy in MDD in Phase 3 clinical trials and was recently FDA approved for the treatment of MDD in adults. Our case describes a patient with relapse of MDD and suicidality who responded well to an approximately two-week course of DXM in combination with BUP. Our case offers an example of DXM/BUP efficacy in the acute inpatient setting, raising the potential of DXM/BUP to modify the course of and effectively treat MDD relapse, and suggests that this may be a plausible strategy for shortening hospital stay.