Combinations of dextromethorphan for the treatment of mood disorders - a review of the evidence.

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.

Study at a glance

Abstract

Major depressive disorder (MDD) is one of the leading causes of disability worldwide. However, many patients do not achieve an adequate clinical improvement with pharmacotherapies targeting monoamine receptors, and the onset of therapeutic benefit typically lags by 4-6 weeks. There is a significant need for mechanistically novel treatments with more rapid efficacy. Combinations of dextromethorphan, an oral N-methyl-D-aspartate (NMDA) receptor antagonist, can potentially fill this gap. US Clinical Trials registration was systematically searched for studies examining the effects of dextromethorphan in mood disorders. Results were gathered via a PubMed search, adding also press releases, and poster presentations. Two case reports and eight clinical trials were identified for the treatment of MDD or treatment resistant depression (TRD); we also reviewed additional studies in bipolar disorder. Clinical studies show that the combinations of dextromethorphan with quinidine or bupropion have been effective in decreasing depressive symptomatology in MDD. However, dextromethorphan studies in adults with TRD or with bipolar depression have shown mixed results. The combination of dextromethorphan and bupropion is a well-tolerated, safe, and efficacious treatment option for adults with MDD. Additional studies analyzing the effects of dextromethorphan and bupropion for TRD and bipolar depression are needed.