Combinations of dextromethorphan for the treatment of mood disorders - a review of the evidence.
Expert review of neurotherapeutics March 1, 2023 Zamfira Parincu, Dan V Iosifescu
Major depressive disorder (MDD) is a leading cause of disability, but many patients do not improve with standard monoamine-targeting drugs, and benefits typically take 4-6 weeks. Combinations of dextromethorphan, an oral NMDA receptor antagonist, may offer faster relief. A systematic search of US Clinical Trials, PubMed, press releases, and poster presentations identified two case reports and eight clinical trials on dextromethorphan for MDD or treatment-resistant depression (TRD), plus additional studies in bipolar disorder. Clinical studies show that dextromethorphan combined with quinidine or bupropion effectively reduces depressive symptoms in MDD. However, results in adults with TRD or bipolar depression were mixed. The dextromethorphan-bupropion combination appears well-tolerated, safe, and efficacious for MDD, but more studies on TRD and bipolar depression are needed.