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

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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.

Plain Language Summary

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.

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References

  1. Chaki S, Watanabe M. Antidepressants in the post-ketamine era: pharmacological approaches targeting the glutamatergic system. Neuropharmacology. 2023;223(109348):1–10.

    Google Scholar 

  2. Davoudian PA, Wilkinson ST. Clinical overview of NMDA-R antagonists and clinical practice. Adv Pharmacol. 2020;89:103–29.

    Article  CAS  PubMed  Google Scholar 

  3. Fenton C, Lee A. Glutamatergic modulators are poorly understood, but promising therapies in depressive disorders. Drugs Ther Perspect. 2022;38(1):7–12.

    Article  Google Scholar 

  4. Henter ID, Park LT, Zarate CA Jr. Novel glutamatergic modulators for the treatment of mood disorders: current status. CNS Drugs. 2021;35(5):527–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Sanches M, Quevedo J, Soares JC. New agents and perspectives in the pharmacological treatment of major depressive disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2021;106(110157):1–9.

    Google Scholar 

  6. Axsome Therapeutics, Inc. AUVELITY (dextromethorphan hydrobromide and bupropion hydrochloride) extended-release tablets, for oral use: US prescribing information. 2022. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=dcefda7c-9a68-278e-e053-2995a90aec79. Accessed 19 June 2023.

  7. Stahl SM. Dextromethorphan/bupropion: a novel oral NMDA (N-methyl-d-aspartate) receptor antagonist with multimodal activity. CNS Spectr. 2019;24(5):461–6.

    Article  PubMed  Google Scholar 

  8. Iosifescu DV, Jones A, O’Gorman C, et al. Efficacy and safety of AXS-05 (dextromethorphan-bupropion) in patients with major depressive disorder: a phase 3 randomized clinical trial (GEMINI). J Clin Psychiatry. 2022;83(4):e1-9.

    Article  Google Scholar 

  9. Tabuteau H, Jones A, Anderson A, et al. Effect of AXS-05 (dextromethorphan-bupropion) in major depressive disorder: a randomized double-blind controlled trial. Am J Psychiatry. 2022;179(7):490–9.

    Article  PubMed  Google Scholar 

  10. Jones A, McIntyre RS, Jacobson M, et al. Impact of AXS-05, an oral NMDA receptor antagonist, on anhedonic symptoms in major depressive disorder [poster no. Th22]. In: American Society of Clinical Psychopharmacology (ASCP) annual meeting. 2022.

  11. Jones A, Streicher C, Thomas Z, et al. 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 [abstract]. CNS Spectr. 2022;28(2):247.

    Article  Google Scholar 

  12. O'Gorman C, Jones A, Tabuteau H. Sustained efficacy with long-term treatment with AXS-05: results from the COMET phase 3 trial, a long-term, open-label study evaluating the efficacy and safety of AXS-05 for the treatment of MDD [abstract no. W29 plus poster]. In: American Society of Clinical Psychopharmacology (ASCP) annual meeting. 2021.

  13. O'Gorman C, Jones A, Tabuteau H. Rapid reduction in suicidal ideation in patients treated with AXS-05, an oral NMDA receptor antagonist with multimodal activity: results from the COMET-SI trial [abstract no. T19 plus poster]. In: American Society of Clinical Psychopharmacology (ASCP) annual meeting. 2021.

  14. Nguyen L, Matsumoto RR. Involvement of AMPA receptors in the antidepressant-like effects of dextromethorphan in mice. Behav Brain Res. 2015;295:26–34.

    Article  CAS  PubMed  Google Scholar 

  15. Nguyen L, Robson MJ, Healy JR, et al. Involvement of sigma-1 receptors in the antidepressant-like effects of dextromethorphan. PLoS ONE. 2014;9(2): e89985.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Schatzberg AF. Understanding the efficacy and mechanism of action of a dextromethorphan-bupropion combination: where does it fit in the NMDA versus mu-opioid story? Am J Psychiatry. 2022;179(7):448–50.

    Article  PubMed  Google Scholar 

  17. Gelenberg A, Freeman MP, Markowitz JC, et al. Practice guideline for the treatment of patients with major depressive disorder. 2010. https://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/mdd.pdf. Accessed 19 June 2023.

  18. McQuaid JR, Buelt A, Capaldi V, et al. The management of major depressive disorder: synopsis of the 2022 US Department of Veterans Affairs and US Department of Defense clinical practice guideline. Ann Intern Med. 2022;175(10):1440–51.

  19. Qaseem A, Owens DK, Etxeandia-Ikobaltzeta I, et al. Nonpharmacologic and pharmacologic treatments of adults in the acute phase of major depressive disorder: a living clinical guideline from the American College of Physicians. Ann Intern Med. 2023;176(2):239–52.

    Article  PubMed  Google Scholar 

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Acknowledgements

The manuscript was reviewed by: M. Hahn, Department of Mental Health, Varisano Hospital Frankfurt Hoechst, and Department of Psychiatry, Psychosomatic and Psychotherapy, University Hospital Frankfurt, Frankfurt, Germany; I. D. Henter, National Institute of Mental Health, Bethesda, MD, USA; A. Singh, Department of Pharmacology, All India Institute of Medical Sciences, Raipur, Chhattisgarh, India. During the peer review process, Axsome Therapeutics, Inc., the marketing authorization holder of dextromethorphan/bupropion, was also offered an opportunity to provide a scientific accuracy review of their data. Changes resulting from comments received were made on the basis of scientific and editorial merit.

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    Hannah A. Blair

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H. A. Blair is a salaried employee of Adis International Ltd/Springer Nature and declares no relevant conflicts of interest. All authors contributed to the review and are responsible for the article content.

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Blair, H.A. Dextromethorphan/bupropion in major depressive disorder: a profile of its use. Drugs Ther Perspect 39, 270–278 (2023). https://doi.org/10.1007/s40267-023-01009-w

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