Dextromethorphan/Bupropion: A Novel Oral NMDA (N-methyl-d-aspartate) Receptor Antagonist with Multimodal Activity

Standard antidepressants boost monoamine levels quickly, but therapeutic effects often take weeks and many patients with major depressive disorder do not respond adequately to first- or second-line monoamine-targeting treatments. The recent approval of the NMDA antagonist esketamine (intranasal) for treatment-resistant depression highlights the need for rapid-acting drugs with different mechanisms. Dextromethorphan/bupropion, an investigational medicine in development, is one such candidate.

Study at a glance

Abstract

Although currently available antidepressants increase monoamine levels soon after the start of treatment, therapeutic benefits are often delayed by several weeks and the majority of patients with major depressive disorder fail to achieve an adequate response to first- or second-line therapies targeting monoamines. The recent approval of the NMDA (N-methyl-d-aspartate) antagonist esketamine given intranasally for treatment-resistant depression has reinforced the need for agents with rapid onset with alternate mechanisms of action. Dextromethorphan/bupropion, an investigational medicine currently in development, is one such candidate.