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

B. McCarthy, Hannah Bunn, Morgan Santalucia, Charlotte Wilmouth, A. Muzyk, Colin M Smith

Clinical Psychopharmacology and Neuroscience July 17, 2023 DOI: 10.9758/cpn.23.1081 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Review Open-label Peer reviewed
Intervention Dextromethorphan-bupropion (Auvelity)
Dose 45−105 mg
Topics Depression
Key findings Dextromethorphan-bupropion is an effective, fast-acting, and well-tolerated treatment for major depressive disorder, producing remission in a large percentage of patients.

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.

Comparable studies

Other narrative reviews on depression, most cited first.

Study Year Design Participants
Synaptic Dysfunction in Depression: Potential Therapeutic Targets 2012 Review
Mindfulness-Based Cognitive Therapy for Depression: A New Approach to Preventing Relapse 2003 Review
Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation Adults with treatment-resistant depression 2021 Review
Classic psychedelics: An integrative review of epidemiology, therapeutics, mystical experience, and brain network function. General population 2019 Integrative review
Sudarshan Kriya Yogic Breathing in the Treatment of Stress, Anxiety, and Depression: Part II—Clinical Applications and Guidelines 2005 Review

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