美国布列根和妇女医院Amit Anand团队比较了电休克治疗（ECT）与氯胺酮治疗非精神病难治性抑郁症的疗效。相关论文发表在2023年5月24日出版的《新英格兰医学杂志》上。

电休克治疗（ECT）和亚麻醉静脉注射氯胺酮目前都用于治疗难治性重度抑郁症，但这两种治疗方法的相对有效性仍不确定。

研究组进行了一项开放标签、随机、非劣效性试验，招募因难治性重度抑郁症而转诊至ECT诊所的患者，并以1:1的比例分配无精神病的难治性重度抑郁症患者接受氯胺酮或ECT治疗。在最初的3周治疗阶段，患者每周接受三次ECT治疗，或每周接受两次氯胺酮（40分钟内每公斤体重0.5 mg）治疗。

主要结局是对治疗的缓解（即，16项抑郁症状快速清单-自我报告的得分比基线下降≥50%；得分范围从0到27，得分越高表示抑郁越严重）。非劣效边缘为-10个百分点。次要结局包括记忆力测试得分和患者报告的生活质量。在最初的治疗阶段后，对有缓解的患者进行为期6个月的随访。

共有403名患者在五个临床机构接受了随机分组；200名患者被分配到氯胺酮组，203名患者被分到ECT组。38名患者在指定治疗开始前退出，最终195名患者接受氯胺酮治疗，170名患者接受ECT。氯胺酮组和ECT组共有55.4%的患者有缓解（差异为14.2个百分点；氯胺酮对ECT的非劣效性P<0.001）。

ECT似乎与治疗3周后记忆回忆的减少有关（霍普金斯言语学习测试中延迟回忆的平均[±SE]T评分下降，氯胺酮组为−0.9±1.1，ECT组为−9.7±1.2；评分范围为−300至200，评分越高表示功能越好），随访期间逐渐恢复。两个试验组患者报告的生活质量改善情况相似。ECT与肌肉骨骼不良反应有关，而氯胺酮与解离有关。

研究结果表明，氯胺酮对无精神病的难治性重度抑郁症的治疗效果不劣于ECT。

附：英文原文

Title: Ketamine versus ECT for Nonpsychotic Treatment-Resistant Major Depression | NEJM

Author: Amit Anand, M.D.,, Sanjay J. Mathew, M.D.,, Gerard Sanacora, M.D., Ph.D.,, James W. Murrough, M.D., Ph.D.,, Fernando S. Goes, M.D.,, Murat Altinay, M.D.,, Amy S. Aloysi, M.D.,, Ali A. Asghar-Ali, M.D.,, Brian S. Barnett, M.D.,, Lee C. Chang, M.D.,, Katherine A. Collins, M.S.W., Ph.D.,, Sara Costi, M.D.,, Sidra Iqbal, M.S.,, Manish K. Jha, M.D.,, Kamini Krishnan, Ph.D.,, Donald A. Malone, M.D.,, Sina Nikayin, M.D.,, Steven E. Nissen, M.D.,, Robert B. Ostroff, M.D.,, Irving M. Reti, M.D.,, Samuel T. Wilkinson, M.D.,, Kathy Wolski, M.P.H.,, and Bo Hu, Ph.D.

Issue&Volume: 2023-05-24

Abstract:

Background

Electroconvulsive therapy (ECT) and subanesthetic intravenous ketamine are both currently used for treatment-resistant major depression, but the comparative effectiveness of the two treatments remains uncertain.

Methods

We conducted an open-label, randomized, noninferiority trial involving patients referred to ECT clinics for treatment-resistant major depression. Patients with treatment-resistant major depression without psychosis were recruited and assigned in a 1:1 ratio to receive ketamine or ECT. During an initial 3-week treatment phase, patients received either ECT three times per week or ketamine (0.5 mg per kilogram of body weight over 40 minutes) twice per week. The primary outcome was a response to treatment (i.e., a decrease of ≥50% from baseline in the score on the 16-item Quick Inventory of Depressive Symptomatology–Self-Report; scores range from 0 to 27, with higher scores indicating greater depression). The noninferiority margin was 10 percentage points. Secondary outcomes included scores on memory tests and patient-reported quality of life. After the initial treatment phase, the patients who had a response were followed over a 6-month period.

Results

A total of 403 patients underwent randomization at five clinical sites; 200 patients were assigned to the ketamine group and 203 to the ECT group. After 38 patients had withdrawn before initiation of the assigned treatment, ketamine was administered to 195 patients and ECT to 170 patients. A total of 55.4% of the patients in the ketamine group and 41.2% of those in the ECT group had a response (difference, 14.2 percentage points; 95% confidence interval, 3.9 to 24.2; P<0.001 for the noninferiority of ketamine to ECT). ECT appeared to be associated with a decrease in memory recall after 3 weeks of treatment (mean [±SE] decrease in the T-score for delayed recall on the Hopkins Verbal Learning Test–Revised, 0.9±1.1 in the ketamine group vs. 9.7±1.2 in the ECT group; scores range from 300 to 200, with higher scores indicating better function) with gradual recovery during follow-up. Improvement in patient-reported quality-of-life was similar in the two trial groups. ECT was associated with musculoskeletal adverse effects, whereas ketamine was associated with dissociation.

Conclusions

Ketamine was noninferior to ECT as therapy for treatment-resistant major depression without psychosis.

DOI: 10.1056/NEJMoa2302399

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2302399