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04-10-2023 | Dextromethorphan | Systematic Review

Dextromethorphan-Bupropion for the Treatment of Depression: A Systematic Review of Efficacy and Safety in Clinical Trials

Authors: Dania Akbar, Taeho Greg Rhee, Felicia Ceban, Roger Ho, Kayla M. Teopiz, Bing Cao, Mehala Subramaniapillai, Angela T. H. Kwan, Joshua D. Rosenblat, Roger S. McIntyre

Published in: CNS Drugs | Issue 10/2023

Abstract

Background

A significant proportion of adults with major depressive disorder (MDD) do not respond to treatments which are currently used in clinical practice such as first-generation monoamine-based antidepressants.

Objectives

The objective of this systematic review was to assess the efficacy, safety, and mechanisms of action of AXS-05, a combination of the NMDA-receptor antagonist dextromethorphan with bupropion, in adults with MDD.

Methods

We searched PubMed, Embase, Google Scholar, and ClinicalTrials.gov for current studies reporting on efficacy and/or safety of AXS-05 in patients with MDD. The search terms included: “AXS-05” OR “dextromethorphan and bupropion” AND “depression”. Studies from database inception to January 2023 were evaluated. Risk of bias was assessed using the Cochrane Risk of Bias tool.

Results

The search yielded 54 studies of which 5 were included. All studies had low risk of bias. Depression severity, measured with the Montgomery–Åsberg Depression Rating Scale (MADRS) significantly decreased as early as 1-week post-treatment from baseline when compared to a placebo-controlled group (LS mean difference 2.2; 95% CI 0.6–3.9; p = 0.007) and at 2 weeks compared to an active control group (LS mean difference 4.7; 95% CI 0.6–8.8; p = 0.024). Treatment efficacy could be maintained for up to 12 months with mean MADRS score reduction of 23 points from baseline. Clinical remission and response rates also improved at week 1 and were maintained for 12 months. The treatment was well-tolerated, with some transient adverse events reported.

Conclusion

Current evidence suggests that the combination of dextromethorphan and bupropion is a well-tolerated, rapid-acting treatment option for adults with MDD. Initial success with AXS-05 supports the mechanistic role of glutamatergeric and sigma 1 signaling in the pathophysiology of MDD.

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Title: Dextromethorphan-Bupropion for the Treatment of Depression: A Systematic Review of Efficacy and Safety in Clinical Trials
Authors: Dania Akbar
Taeho Greg Rhee
Felicia Ceban
Roger Ho
Kayla M. Teopiz
Bing Cao
Mehala Subramaniapillai
Angela T. H. Kwan
Joshua D. Rosenblat
Roger S. McIntyre
Publication date: 04-10-2023
Publisher: Springer International Publishing
Keywords: Dextromethorphan
Bupropion
Antidepressant Drugs
Antidepressant Drugs
Mood Disorders
Affective Disorder
Published in: CNS Drugs / Issue 10/2023
Print ISSN: 1172-7047
Electronic ISSN: 1179-1934
DOI: https://doi.org/10.1007/s40263-023-01032-5

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Dextromethorphan-Bupropion for the Treatment of Depression: A Systematic Review of Efficacy and Safety in Clinical Trials

Abstract

Background

Objectives

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Objectives

Methods

Results

Conclusion

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