From the Department of Psychiatry, Mass General Brigham, and Harvard Medical School - both in Boston (A.A.); Baylor College of Medicine (S.J.M., A.A.A.-A., S.I., L.C.C.) and Michael E. DeBakey Veterans Affairs Medical Center, Houston (S.J.M., A.A.A.-A., S.I.), and the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas (M.K.J.) - all in Texas; the Department of Psychiatry, Yale University School of Medicine, New Haven, CT (G.S., S.N., R.B.O., S.T.W.); the Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York (J.W.M., A.S.A.), and the Division of Clinical Research, Nathan Kline Institute for Psychiatric Research, Orangeburg (K.A.C.) - both in New York; the Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore (F.S.G., I.M.R.); the Department of Psychiatry and Psychology, Center for Behavioral Health, Neurological Institute (M.A., B.S.B., D.A.M.), Lou Ruvo Center for Brain Health (K.K.), Cleveland Clinic Center for Clinical Research (C5Research), Heart, Vascular, and Thoracic Institute (S.E.N., K.W.), and the Department of Quantitative Health Sciences (B.H.), Cleveland Clinic, Cleveland; and the Psychopharmacology Laboratory, Department of Psychiatry, University of Oxford, Oxford, United Kingdom (S.C.).
N Engl J Med. 2023 Jun 22;388(25):2315-2325. doi: 10.1056/NEJMoa2302399. Epub 2023 May 24.
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. (Funded by the Patient-Centered Outcomes Research Institute; ELEKT-D ClinicalTrials.gov number, NCT03113968.).
背景：电抽搐治疗（ECT）和亚麻醉静脉注射氯胺酮目前均用于治疗抵抗性重度抑郁症，但两种治疗方法的疗效比较仍不确定。
方法：我们开展了一项开放标签、随机、非劣效性试验，纳入因治疗抵抗性重度抑郁症而被转至 ECT 诊所的患者。我们招募了没有精神病的治疗抵抗性重度抑郁症患者，并按照 1:1 的比例随机分配至接受氯胺酮或 ECT 治疗。在最初的 3 周治疗阶段，患者每周接受 ECT 治疗 3 次或每周接受氯胺酮（0.5 毫克/千克体重，静脉输注 40 分钟）治疗 2 次。主要结局是治疗应答（即，16 项简明抑郁症状自评量表自评报告的基线评分下降≥50%；评分范围为 0 至 27，得分越高表示抑郁程度越严重）。非劣效性边界为-10 个百分点。次要结局包括记忆测试评分和患者报告的生活质量。在初始治疗阶段后，对有应答的患者进行了 6 个月的随访。
结果：在 5 个临床地点共对 403 名患者进行了随机分组；200 名患者被分配至氯胺酮组，203 名患者被分配至 ECT 组。在开始接受指定治疗前有 38 名患者退出，之后对 195 名患者给予氯胺酮治疗，对 170 名患者给予 ECT 治疗。氯胺酮组有 55.4%的患者和 ECT 组有 41.2%的患者有应答（差异为 14.2 个百分点；95%置信区间为 3.9 至 24.2；氯胺酮非劣效于 ECT，P<0.001）。ECT 治疗 3 周后似乎会导致记忆回忆能力下降（霍普金斯词语学习测验修订版延迟回忆 T 评分的平均[±SE]下降值，氯胺酮组为-0.9±1.1，ECT 组为-9.7±1.2；评分范围为-300 至 200，得分越高表示功能越好），但在随访期间逐渐恢复。两组患者报告的生活质量改善情况相似。ECT 治疗相关的不良反应主要为肌肉骨骼不适，而氯胺酮治疗相关的不良反应主要为分离体验。
结论：氯胺酮作为治疗无精神病性症状的治疗抵抗性重度抑郁症的疗法不劣于 ECT。（由患者导向的结果研究所资助；ELEKT-D ClinicalTrials.gov 编号，NCT03113968。）
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