De Maricourt P, Jay T, Goncalvès P, Lôo H, Gaillard R
Service hospitalo-universitaire de santé mentale et de thérapeutique, centre hospitalier Sainte-Anne, université Paris-Descartes, 1, rue Cabanis, 75014 Paris, France; Inserm UMR 894, centre de psychiatrie et neurosciences, université Paris-Descartes, Sorbonne, Paris Cité, Paris, France.
Inserm UMR 894, centre de psychiatrie et neurosciences, université Paris-Descartes, Sorbonne, Paris Cité, Paris, France.
Encephale. 2014 Feb;40(1):15-23. doi: 10.1016/j.encep.2013.09.001. Epub 2014 Jan 14.
Depressive disorders have a major impact on public health. They are prevalent and disabling, with high economic burden for society. Antidepressants have a delayed action and at least one third of patients do not achieve adequate response. The recent discovery of ketamine's unique antidepressant properties, with rapid onset of response and high rate of responders opens new perspectives for treatment-resistant depression (TRD).
The aim of this article is to summarize preclinical trials and clinical trials demonstrating ketamine antidepressant properties and to review the different modalities of use.
Most clinical studies used ketamine with a single subanesthetic intravenous administration in patients with treatment-resistant depression, demonstrating a rapid but transient antidepressant response with high response rates. To prevent relapse and maintain the initial benefits, few studies have shown the interest of serial infusions of ketamine, while others combined ketamine and electroconvulsive therapy using the former as an anesthetic. So far, relay treatments with glutamatergic agents such as riluzole are disappointing. Although most studies were conducted in patients with TRD in recurrent depression or bipolar disorder, efficacy in acutely suicidal patients is promising.
Our review highlights the increasing interest in the use of ketamine in the treatment of treatment-resistant depression. Although a widespread use of ketamine as an antidepressant in routine clinical settings seems limited by psychotomimetic effects and the lack of strategy to maintain initial benefits, ketamine or related drugs might be used to target specific conditions, such as bipolar depression or high suicide risk.
抑郁症对公众健康有重大影响。它们普遍存在且使人丧失能力，给社会带来高昂的经济负担。抗抑郁药起效延迟，至少三分之一的患者未获得充分缓解。氯胺酮独特的抗抑郁特性的最新发现，即起效迅速且缓解率高，为难治性抑郁症（TRD）的治疗开辟了新前景。
本文旨在总结证明氯胺酮抗抑郁特性的临床前试验和临床试验，并综述其不同的使用方式。
大多数临床研究在难治性抑郁症患者中使用单次亚麻醉剂量静脉注射氯胺酮，显示出快速但短暂的抗抑郁反应且缓解率高。为防止复发并维持初始疗效，少数研究表明氯胺酮连续输注有一定作用，而其他研究则将氯胺酮与电休克治疗联合使用，将前者用作麻醉剂。到目前为止，使用如利鲁唑等谷氨酸能药物进行接力治疗效果不佳。尽管大多数研究是在复发性抑郁症或双相情感障碍的难治性抑郁症患者中进行的，但在急性有自杀倾向患者中的疗效很有前景。
我们的综述强调了氯胺酮在难治性抑郁症治疗中的应用越来越受到关注。尽管氯胺酮作为抗抑郁药在常规临床环境中的广泛应用似乎受到拟精神病作用以及缺乏维持初始疗效策略的限制，但氯胺酮或相关药物可能用于针对特定情况，如双相抑郁症或高自杀风险。
