<p><strong>Declarations</strong></p> <p><strong>Funding</strong> The preparation of this review was not supported by any external funding.</p> <p><strong>Authorship and Conflict of interest</strong> During the peer review process the manufacturer of the agent under review was offered an opportunity to comment on the article. Changes resulting from any comments received were made by the authors on the basis of scientific completeness and accuracy. Susan J. Keam is a contracted 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.</p> <p><strong>Ethics approval, Consent to participate, Consent to publish, Availability of data and material, Code availability</strong> not applicable</p> <p>Additional information about this Adis Drug Review can be found<a href="https://www.springer.com/gp/adis/products-services/adis-journals-newsletters/adis-drug-reviews" target="_blank"> here.</a></p> <p><strong>Abstract</strong></p> <p>An oral, fixed-dose combination of dextromethorphan hydrobromide [an uncompetitive <em>N</em>-methyl-D-aspartate (NMDA) receptor antagonist and sigma-1 receptor agonist] and the antidepressant bupropion hydrochloride (an aminoketone and CYP2D6 inhibitor that increases dextromethorphan bioavailability) [AUVELITYTM; dextromethorphan/bupropion], is being developed by Axsome Therapeutics, Inc. for the treatment of major depressive disorder (MDD), Alzheimer’s disease agitation and smoking cessation. Dextromethorphan/bupropion was approved in the USA in August 2022 for the treatment of MDD in adults. This article summarizes the milestones in the development of dextromethorphan/bupropion leading to this first approval for the treatment of adults with MDD.  </p> <p>© Springer Nature Switzerland AG 2022</p>