Department of Psychiatry,University of British Columbia,Vancouver, BC,Canada.
Neuromodulation Research Clinic,Douglas Mental Health University Institute and McGill University,Montréal, Québec,Canada.
Psychol Med. 2015 Mar;45(4):693-704. doi: 10.1017/S0033291714001603. Epub 2014 Jul 10.
There is growing interest in glutamatergic agents in depression, particularly ketamine, a glutamate N-methyl-d-aspartate (NMDA) receptor antagonist. We aimed to assess the efficacy of ketamine in major depressive episodes.
We searched EMBASE, PsycINFO, CENTRAL, and Medline from 1962 to January 2014 to identify double-blind, randomized controlled trials with allocation concealment evaluating ketamine in major depressive episodes. Clinical remission, response and depressive symptoms were extracted by two independent raters. The primary outcome measure was clinical remission at 24 h, 3 days and 7 days post-treatment. Analyses employed a random-effects model.
Data were synthesized from seven RCTs employing an intravenous infusion and one RCT employing intranasal ketamine, representing 73 subjects in parallel arms and 110 subjects in cross-over designs [n = 34 with bipolar disorder (BD), n = 149 with major depressive disorder (MDD)]. Ketamine was associated with higher rates of clinical remission relative to comparator (saline or midazolam) at 24 h [OR 7.06, number needed to treat (NNT) = 5], 3 days (OR 3.86, NNT = 6), and 7 days (OR 4.00, NNT = 6), as well as higher rates of clinical response at 24 h (OR 9.10, NNT = 3), 3 days (OR 6.77, NNT = 3), and 7 days (OR 4.87, NNT = 4). A standardized mean difference of 0.90 in favor of ketamine was observed at 24 h based on depression rating scale scores, with group comparisons revealing greater efficacy in unipolar depression compared to bipolar depression (1.07 v. 0.68). Ketamine was associated with transient psychotomimetic effects, but no persistent psychosis or affective switches.
Our meta-analysis suggests that single administrations ketamine are efficacious in the rapid treatment of unipolar and bipolar depression. Additional research is required to determine optimal dosing schedules, route, treatment schedules, and the potential efficacy of other glutamatergic agents.
人们对谷氨酸能药物在抑郁症中的作用越来越感兴趣，尤其是氯胺酮，一种谷氨酸 N-甲基-D-天冬氨酸（NMDA）受体拮抗剂。我们旨在评估氯胺酮治疗重度抑郁症发作的疗效。
我们检索了 EMBASE、PsycINFO、CENTRAL 和 Medline 从 1962 年到 2014 年 1 月，以确定双盲、随机对照试验，评估氯胺酮治疗重度抑郁症发作。两名独立的评估者提取临床缓解、反应和抑郁症状。主要的疗效指标是治疗后 24 小时、3 天和 7 天的临床缓解。分析采用随机效应模型。
数据综合了七项 RCT，采用静脉输注，一项 RCT 采用鼻腔内氯胺酮，分别代表平行臂 73 例和交叉设计 110 例[双相障碍（BD）34 例，重性抑郁障碍（MDD）149 例]。与对照组（生理盐水或咪达唑仑）相比，氯胺酮在 24 小时[OR 7.06，需要治疗的人数（NNT）=5]、3 天[OR 3.86，NNT = 6]和 7 天[OR 4.00，NNT = 6]时的临床缓解率更高，在 24 小时[OR 9.10，NNT = 3]、3 天[OR 6.77，NNT = 3]和 7 天[OR 4.87，NNT = 4]时的临床反应率更高。基于抑郁评定量表评分，24 小时时氯胺酮的标准化均数差为 0.90，组间比较显示单相抑郁的疗效优于双相抑郁（1.07 比 0.68）。氯胺酮与短暂的精神病样效应相关，但没有持续的精神病或情感转换。
我们的荟萃分析表明，单次给予氯胺酮治疗单相和双相抑郁症是有效的。需要进一步研究以确定最佳剂量方案、途径、治疗方案以及其他谷氨酸能药物的潜在疗效。
