Dextromethorphan/bupropion in major depressive disorder: a profile of its use
Hannah A. Blair
Drugs & therapy perspectives July 6, 2023 DOI: 10.1007/s40267-023-01009-w (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Randomized Double-blind Peer reviewed |
|---|---|
| Intervention | Dextromethorphan/bupropion |
| Topics | Depression |
| Key findings | Dextromethorphan/bupropion rapidly improved depressive symptoms and remission rates compared with placebo or bupropion alone in adults with major depressive disorder. |
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.
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 |
Citations in the library
Cited by 3
- Molecular Mechanisms of Emerging Antidepressant Strategies: From Ketamine to Neuromodulation International Journal of Molecular Sciences December 28, 2025
- Next-Generation Pharmacotherapy for Depressive Disorders: From Novel Compounds to Optimized Use of Available Drugs. Drug Design, Development and Therapy 2026
- Profiling the combination of bupropion and dextromethorphan as a treatment option for major depressive disorder. Expert Review of Neurotherapeutics September 1, 2024
Cites 6
- AXS-05 (DEXTROMETHORPHAN-BUPROPION) Improves Depressive Symptoms and Functioning in Patients With One Prior Treatment Failure: Results From the Evolve Long-Term, Open Label Study CNS Spectrums April 1, 2023
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and 1 more in the library