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

A fixed-dose combination of dextromethorphan and bupropion (AUVELITY) is an effective and generally well-tolerated treatment for adults with major depressive disorder. In randomized, double-blind clinical trials, it produced early, clinically meaningful improvements in depressive symptoms, remission rates, and functional disability compared with placebo or bupropion alone, with benefits sustained over the longer term. The combination was not associated with increased psychotomimetic effects, weight gain, or suicidal behaviors; common adverse events were dizziness and nausea.

Study at a glance

Abstract

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. Major depressive disorder (MDD) is one of the most common mental health conditions in the world and poses a serious public health problem. Some patients do not respond to conventional antidepressants, prompting the need for new treatments that are effective and fast-acting. A fixed-dose combination tablet containing dextromethorphan and bupropion (AUVELITY®) has been approved for the treatment of MDD in adults. Evidence for the efficacy of dextromethorphan/bupropion has been demonstrated in clinical trials in patients with MDD, where it rapidly improved depressive symptoms compared with placebo or sustained-release (SR) bupropion within 1–2 weeks. Dextromethorphan/bupropion also improved remission rates compared with placebo or bupropion SR. The benefits of dextromethorphan/bupropion were maintained during longer term treatment. Dextromethorphan/bupropion was generally well tolerated; the most common adverse events were dizziness and nausea. Given its efficacy and tolerability profile, dextromethorphan/bupropion is a useful treatment option for adults with MDD.