Dextromethorphan-bupropion (Auvelity) for the Treatment of Major Depressive Disorder

Dextromethorphan-bupropion (Auvelity), an FDA-approved treatment for major depressive disorder in adults, is an effective, fast-acting, and well-tolerated option. In a phase 3 trial, the 45–105 mg dose produced significant reductions in Montgomery–Åsberg Depression Rating Scale scores compared to placebo. A phase 2 trial showed similar significant reductions versus bupropion alone. Improvements appeared within two weeks in both trials, with significantly higher remission and response rates. Two long-term open-label studies found large reductions maintained through 12 and 15 months, with remission rates approaching 70% and response rates above 80%. Common adverse events were mild-to-moderate.

Study at a glance

Abstract

Depression is a significant cause of morbidity and mortality globally. Although various pharmacologic options exist for depression, treatments are limited by delayed or incomplete therapeutic response, low rates of remission, and adverse effects necessitating effective, fast-acting, and better tolerated alternatives. The purpose of this review is to describe the safety and efficacy of dextromethorphan-bupropion (Auvelity), a Food and Drug Administration approved treatment for major depressive disorder in adults. Dextromethorphan modulates glutamate signaling through uncompetitive antagonism of N-methyl-D-aspartate receptors and sigma-1 agonism, while bupropion increases the bioavailability of dextromethorphan by CYP2D6 inhibition. In a phase 3 trial with dextromethorphan-bupropion 45−105 mg for patients with major depressive disorder saw significant reductions in their Montgomery–Åsberg Depression Rating Scale total scores compared to placebo. A phase 2 trial comparing dextromethorphan-bupropion 45−105 mg to bupropion monotherapy led to significant reduction in Montgomery-Åsberg Depression Rating Scale score. Changes in Montgomery–Åsberg Depression Rating Scale with dextromethorphan-bupropion were seen within two weeks in both clinical trials. Remission and response rates were significantly higher with dextromethorphan-bupropion in both studies. The medication was well-tolerated in both trials, with the most common adverse events being rated as mild-to-moderate. Two long-term, open-label studies with dextromethorphan-bupropion saw large reductions in Montgomery–Åsberg Depression Rating Scale scores that were maintained through 12 and 15 months of treatment. In both long-term studies, remission rates approached 70%, while response rates were greater than 80%. These data suggest that dextromethorphan-bupropion is an effective, fast-acting, and well tolerated option for depression treatment and produced remission in a large percentage of patients.