From the Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, Bethesda, MD.
J Clin Psychopharmacol. 2023;43(5):422-427. doi: 10.1097/JCP.0000000000001738. Epub 2023 Jul 26.
Approximately one third of individuals with major depressive disorder have treatment-resistant depression (TRD). Glutamatergic modulators such as the N -methyl- d -aspartate receptor antagonist ketamine have rapid and robust antidepressant effects, but their use has been limited by accessibility and route of administration. This open-label pilot study assessed the adjunctive antidepressant efficacy of dextromethorphan/quinidine (DM/Q) in TRD.
Inpatients with TRD (n = 17, 40.8 ± 12.3 years; 9 females/8 males) received adjunctive open-label DM/Q (20 mg/10 mg) up to 3 times daily. The study had no set endpoint; participants were followed until they discontinued DM/Q or were discharged. Montgomery-Asberg Depression Rating Scale (MADRS) scores were obtained at baseline (before DM/Q administration) and regularly during hospitalization. Full response was defined as a ≥50% reduction in baseline MADRS score, partial response as a 25% to 50% decrease in baseline MADRS score, and nonresponse as a <25% reduction or an increase in baseline MADRS score.
The 17 inpatients received open-label DM/Q for 5.1 ± 2.7 weeks. Forty-seven percent of participants responded to DM/Q-12% achieved a full response and 35% achieved a partial response. The largest MADRS difference observed at any time point was -6.4 ± 8.4 (-21.0% ± 29.9%), and the MADRS difference observed at time of DM/Q discontinuation or hospital discharge was -4.8 ± 8.4 (-15.9% ± 29.7%). Twenty-four percent of participants experienced a nonserious adverse event; none experienced a serious adverse event.
In this open-label pilot study, 47% of participants responded to adjunctive DM/Q, which was well tolerated. Larger placebo-controlled trials are needed to determine the real-world efficacy of DM/Q.
大约三分之一的重度抑郁症患者患有治疗抵抗性抑郁症（TRD）。谷氨酸能调节剂，如 N -甲基- D -天冬氨酸受体拮抗剂氯胺酮，具有快速而强大的抗抑郁作用，但由于其可及性和给药途径的限制，其应用受到限制。这项开放标签的初步研究评估了辅助性右美沙芬/奎尼丁（DM/Q）在 TRD 中的抗抑郁作用。
TRD 住院患者（n=17，40.8±12.3 岁；9 名女性/8 名男性）接受辅助性开放标签 DM/Q（20mg/10mg），每日最多 3 次。该研究没有设定终点；参与者继续接受 DM/Q治疗，直到他们停止或出院。入院前（开始 DM/Q 治疗前）和住院期间定期使用蒙哥马利-阿斯伯格抑郁评定量表（MADRS）评分。完全反应定义为基线 MADRS 评分降低≥50%，部分反应定义为基线 MADRS 评分降低 25%至 50%，无反应定义为基线 MADRS 评分降低<25%或升高。
17 名住院患者接受了为期 5.1±2.7 周的开放标签 DM/Q 治疗。47%的参与者对 DM/Q 有反应-12%达到完全反应，35%达到部分反应。任何时间点观察到的最大 MADRS 差异为-6.4±8.4（-21.0%±29.9%），DM/Q 停药或出院时的 MADRS 差异为-4.8±8.4（-15.9%±29.7%）。24%的参与者出现非严重不良事件；无严重不良事件。
在这项开放标签的初步研究中，47%的参与者对辅助性 DM/Q 有反应，且耐受性良好。需要更大规模的安慰剂对照试验来确定 DM/Q 的实际疗效。
