Ketamine augmentation of electroconvulsive therapy to improve neuropsychological and clinical outcomes in depression (Ketamine-ECT): a multicentre, double-blind, randomised, parallel-group, superiority trial.
Ketamine augmentation of electroconvulsive therapy to improve neuropsychological and clinical outcomes in depression (Ketamine-ECT): a multicentre, double-blind, randomised, parallel-group, superiority trial.
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DOI：
10.1016/s2215-0366(17)30077-9
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发表时间：
2017-05
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影响因子：
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通讯作者：
Ketamine-ECT Study team
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作者：
Anderson IM;Blamire A;Branton T;Clark R;Downey D;Dunn G;Easton A;Elliott R;Elwell C;Hayden K;Holland F;Karim S;Loo C;Lowe J;Nair R;Oakley T;Prakash A;Sharma PK;Williams SR;McAllister-Williams RH;Ketamine-ECT Study team
电休克疗法（ECT）的使用受到对其认知不良反应的担忧的限制。初步证据表明，给予谷氨酸拮抗剂氯胺酮与ECT可能会减轻认知不良反应，加速症状改善;我们在一项低剂量氯胺酮的随机试验中对此进行了测试。在这项多中心、随机、平行组研究中，在英格兰北部7个国家卫生服务信托基金的11个ECT套房中，我们招募了严重抑郁症患者，他们被诊断为患有单相或双相抑郁发作，根据DSM-IV标准定义为中度或重度，年龄至少18岁，并且能够并愿意提供参与本研究的书面同意书。在ECT过程中，患者被随机（1：1）分配至氯胺酮（0.5 mg/kg静脉推注）或生理盐水麻醉。患者、评估和ECT治疗组对治疗分配设盲，但给予研究药物的麻醉师不设盲。我们使用高斯重复测量模型分析了所有首次接受ECT治疗的患者的主要结局，即4次ECT治疗后的霍普金斯言语学习测验修订版延迟言语回忆（HVLT-R-DR）。在同一人群中，通过不良反应监测评估安全性。本试验注册了国际标准随机对照试验编号ISRCTN 14689382。在2012年12月初至2015年6月中旬期间，对628名患者进行了资格筛选，其中79名被随机分配到治疗组（氯胺酮组40名，生理盐水组39名）。氯胺酮（平均5.17，SD 2.92）与生理盐水（5.54，3.42）相比，对主要结局无获益（HVLT-R-DR;平均差异为-0.43 [95%CI-1.73至0.87]）。33例氯胺酮治疗患者中有15例（45%）发生了至少一次不良事件，而37例生理盐水治疗患者中有10例（27%）发生了至少一次不良事件，其中33例患者中有2例（6%）发生了氯胺酮引起的短暂心理效应。精神病不良事件在两组中最常见（氯胺酮组22例不良事件中有6例[27%]，生理盐水组13例不良事件中有7例[54%]）。尽管使用的样本量较小，但未发现氯胺酮获益的证据;然而，结果排除了大于小至中度获益的证据，置信度为95%。结果不支持在常规ECT治疗中使用连续性低剂量氯胺酮。国家卫生研究所（NIHR）的疗效和机制评估（EME）计划，MRC和NIHR的伙伴关系。
The use of electroconvulsive therapy (ECT) is limited by concerns about its cognitive adverse effects. Preliminary evidence suggests that administering the glutamate antagonist ketamine with ECT might alleviate cognitive adverse effects and accelerate symptomatic improvement; we tested this in a randomised trial of low-dose ketamine. In this multicentre, randomised, parallel-group study in 11 ECT suites serving inpatient and outpatient care settings in seven National Health Service trusts in the North of England, we recruited severely depressed patients, who were diagnosed as having unipolar or bipolar depressive episodes defined as moderate or severe by DSM-IV criteria, aged at least 18 years, and were able and willing to provide written consent to participate in the study. Patients were randomly assigned (1:1) to ketamine (0·5 mg/kg intravenous bolus) or saline adjunctive to the anaesthetic for the duration of their ECT course. Patients and assessment and ECT treatment teams were masked to treatment allocation, although anaesthetists administering the study medication were not. We analysed the primary outcome, Hopkins Verbal Learning Test-Revised delayed verbal recall (HVLT-R-DR) after four ECT treatments, using a Gaussian repeated measures model in all patients receiving the first ECT treatment. In the same population, safety was assessed by adverse effect monitoring. This trial was registered with International Standard Randomised Controlled Trial Number, number ISRCTN14689382. Between early December, 2012, and mid-June, 2015, 628 patients were screened for eligibility, of whom 79 were randomly assigned to treatment (40 in the ketamine group vs 39 in the saline group). Ketamine (mean 5·17, SD 2·92), when compared with saline (5·54, 3·42), had no benefit on the primary outcome (HVLT-R-DR; difference in means −0·43 [95% CI −1·73 to 0·87]). 15 (45%) of 33 ketamine-treated patients compared with 10 (27%) of 37 patients receiving saline experienced at least one adverse event which included two (6%) of 33 patients who had ketamine-attributable transient psychological effects. Psychiatric adverse events were the most common in both groups (six [27%] of 22 adverse events in the ketamine group vs seven [54%] of 13 in the saline group). No evidence of benefit for ketamine was found although the sample size used was small; however, the results excluded greater than a small to moderate benefit with 95% confidence. The results do not support the use of adjunctive low-dose ketamine in routine ECT treatment. National Institute for Health Research (NIHR) Efficacy and Mechanism Evaluation (EME) programme, an MRC and NIHR partnership.