Antidepressant efficacy of ketamine in treatment-resistant major depression: a two-site randomized controlled trial.
Antidepressant efficacy of ketamine in treatment-resistant major depression: a two-site randomized controlled trial.
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DOI：
10.1176/appi.ajp.2013.13030392
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发表时间：
2013-10
期刊：
影响因子：
--
通讯作者：
Mathew SJ
中科院分区：
文献类型：
--
作者：
Murrough JW;Iosifescu DV;Chang LC;Al Jurdi RK;Green CE;Perez AM;Iqbal S;Pillemer S;Foulkes A;Shah A;Charney DS;Mathew SJ
氯胺酮是一种谷氨酸N-甲基-d-天冬氨酸（NMDA）受体拮抗剂，已显示出快速的抗抑郁作用，但先前研究中的小研究组和不充分的对照条件妨碍了明确的结论。作者评估了氯胺酮在一大群难治性抑郁症患者中的快速抗抑郁疗效。这是一项比较氯胺酮单次输注与活性安慰剂对照条件（麻醉剂咪达唑仑）的双中心、平行组、随机对照试验。在双盲条件下，将经历重性抑郁发作的难治性重性抑郁症患者随机分配接受氯胺酮或咪达唑仑单次静脉输注，比例为2：1（N=73）。主要结局是给药后24小时抑郁严重程度的变化，由蒙哥马利-埃斯伯格抑郁评定量表（MADRS）评估。氯胺酮组治疗后24 h MADRS评分改善程度大于咪达唑仑组。校正基线评分和临床试验机构后，氯胺酮组的MADRS评分比咪达唑仑组低7.95分（95%置信区间[CI]，3.20 - 12.71）。氯胺酮组24小时缓解的可能性大于咪达唑仑组（比值比，2.18; 95% CI，1.21 - 4.14），缓解率分别为64%和28%。氯胺酮在优化的研究设计中显示出快速的抗抑郁作用，进一步支持NMDA受体调节作为加速改善重度和慢性抑郁症的新机制。在临床实践中实施之前，需要更多关于反应持久性和安全性的信息。
Ketamine, a glutamate N-methyl-d-aspartate (NMDA) receptor antagonist, has shown rapid antidepressant effects, but small study groups and inadequate control conditions in prior studies have precluded a definitive conclusion. The authors evaluated the rapid antidepressant efficacy of ketamine in a large group of patients with treatment-resistant major depression. This was a two-site, parallel-arm, randomized controlled trial of a single infusion of ketamine compared to an active placebo control condition, the anesthetic midazolam. Patients with treatment-resistant major depression experiencing a major depressive episode were randomly assigned under double-blind conditions to receive a single intravenous infusion of ketamine or midazolam in a 2:1 ratio (N=73). The primary outcome was change in depression severity 24 hours after drug administration, as assessed by the Montgomery-Åsberg Depression Rating Scale (MADRS). The ketamine group had greater improvement in the MADRS score than the midazolam group 24 hours after treatment. After adjustment for baseline scores and site, the MADRS score was lower in the ketamine group than in the midazolam group by 7.95 points (95% confidence interval [CI], 3.20 to 12.71). The likelihood of response at 24 hours was greater with ketamine than with midazolam (odds ratio, 2.18; 95% CI, 1.21 to 4.14), with response rates of 64% and 28%, respectively. Ketamine demonstrated rapid antidepressant effects in an optimized study design, further supporting NMDA receptor modulation as a novel mechanism for accelerated improvement in severe and chronic forms of depression. More information on response durability and safety is required before implementation in clinical practice.
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影响因子：
64.8
作者：
Autry, Anita E.;Adachi, Megunai;Nosyreva, Elena;Na, Elisa S.;Los, Maarten F.;Cheng, Peng-fei;Kavalali, Ege T.;Monteggia, Lisa M.
通讯作者：
Monteggia, Lisa M.
DOI：
10.1126/science.1190287
发表时间：
2010-08-20
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Li N;Lee B;Liu RJ;Banasr M;Dwyer JM;Iwata M;Li XY;Aghajanian G;Duman RS
通讯作者：
Duman RS
影响因子：
10.6
作者：
aan het Rot, Marije;Collins, Katherine A.;Mathew, Sanjay J.
通讯作者：
Mathew, Sanjay J.
影响因子：
10.6
作者：
Berman, RM;Cappiello, A;Krystal, JH
通讯作者：
Krystal, JH
影响因子：
64.8
作者：
Collins, Pamela Y.;Patel, Vikram;Joestl, Sarah S.;March, Dana;Insel, Thomas R.;Daar, Abdallah S.
通讯作者：
Daar, Abdallah S.