Dextromethorphan/bupropion in major depressive disorder: a profile of its use

Dextromethorphan/bupropion (AUVELITY®), an oral, fixed-dose combination of dextromethorphan hydrobromide and bupropion hydrochloride, is a useful treatment option for adults with major depressive disorder (MDD). Dextromethorphan is an uncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist and sigma-1 receptor agonist. The antidepressant bupropion (an aminoketone and cytochrome P450 2D6 inhibitor) increases the bioavailability of dextromethorphan. In randomized, double-blind, clinical trials in patients with MDD, dextromethorphan/bupropion demonstrated early, clinically meaningful improvements in depressive symptoms, remission rates, and functional disability compared with placebo or sustained-release (SR) bupropion, with these improvements sustained over the longer term. Dextromethorphan/bupropion was generally well tolerated, including in the long term, and was not associated with a signal for increased psychotomimetic effects, weight gain, or increased suicidal behaviors.