Temerty Faculty of Medicine, University of Toronto, Canada.
Department of Pharmacology, University of Toronto, Toronto, Canada.
Expert Opin Emerg Drugs. 2021 Mar;26(1):63-74. doi: 10.1080/14728214.2021.1898588. Epub 2021 Mar 12.
The large percentage of adults with major depressive disorder (MDD) insufficiently responding and/or tolerating conventional monoamine-based antidepressants invites the need for mechanistically novel treatments. Convergent evidence implicates glutamatergic signaling as a potential therapeutic target in MDD.
The synthesis herein of preclinical and clinical studies indicates that dextromethorphan (DXM) is well tolerated and exhibits clinically significant antidepressant effects; DXM combined with bupropion has demonstrated replicated and relatively rapid onset efficacy in adults with MDD. DXM efficacy has been preliminarily reported in adults with bipolar depression. The combination of DXM and bupropion represents a pharmacokinetic and pharmacodynamic synergy which may account for the rapidity of action in MDD.
The combination of DXM and bupropion is a safe, well tolerated and efficacious treatment option in adults with MDD. Priority questions are whether DXM/bupropion is uniquely effective across discrete domains of psychopathology (e.g. anhedonia, reward processing, general cognitive systems) and/or whether it is able to significantly improve patient-reported outcomes (e.g. quality of life, psychosocial functioning). The availability of ketamine/esketamine and DXM/bupropion instantiates the relevance of glutamate as a treatment target in MDD. Studies in bipolar depression with DXM/bupropion are warranted as well as in MDD with suicidality.
大量患有重度抑郁症（MDD）的成年人对常规单胺类抗抑郁药反应不足和/或耐受，这需要新的治疗机制。大量证据表明，谷氨酸能信号是 MDD 的潜在治疗靶点。
本文对临床前和临床研究进行综述，表明右美沙芬（DXM）具有良好的耐受性，并表现出显著的临床抗抑郁作用；DXM 与安非他酮联合使用在 MDD 成人中显示出可复制和相对快速的疗效。DXM 在双相抑郁成人中也有初步疗效报告。DXM 和安非他酮的联合使用代表了一种药代动力学和药效学的协同作用，这可能是 MDD 起效迅速的原因。
DXM 和安非他酮的联合使用是 MDD 成人安全、耐受性好且有效的治疗选择。优先考虑的问题是 DXM/安非他酮是否在精神病学的不同领域（如快感缺失、奖励处理、一般认知系统）具有独特的疗效，或者是否能显著改善患者报告的结果（如生活质量、社会心理功能）。氯胺酮/ Esketamine 和 DXM/安非他酮的出现证实了谷氨酸作为 MDD 治疗靶点的相关性。有必要在双相抑郁中进行 DXM/安非他酮的研究，以及在有自杀意念的 MDD 中进行研究。
