Abdallah Chadi G, Sanacora Gerard, Duman Ronald S, Krystal John H
Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06511; email:
Annu Rev Med. 2015;66:509-23. doi: 10.1146/annurev-med-053013-062946. Epub 2014 Oct 17.
Ketamine is the prototype for a new generation of glutamate-based antidepressants that rapidly alleviate depression within hours of treatment. Over the past decade, there has been replicated evidence demonstrating the rapid and potent antidepressant effects of ketamine in treatment-resistant depression. Moreover, preclinical and biomarker studies have begun to elucidate the mechanism underlying the rapid antidepressant effects of ketamine, offering a new window into the biology of depression and identifying a plethora of potential treatment targets. This article discusses the efficacy, safety, and tolerability of ketamine, summarizes the neurobiology of depression, reviews the mechanisms underlying the rapid antidepressant effects of ketamine, and discusses the prospects for next-generation rapid-acting antidepressants.
氯胺酮是新一代基于谷氨酸的抗抑郁药的原型,这类药物在治疗数小时内就能迅速缓解抑郁症状。在过去十年中,有重复性证据表明氯胺酮对难治性抑郁症具有快速且强效的抗抑郁作用。此外,临床前研究和生物标志物研究已开始阐明氯胺酮快速抗抑郁作用的潜在机制,为抑郁症生物学研究打开了一扇新窗口,并确定了大量潜在治疗靶点。本文将探讨氯胺酮的疗效、安全性和耐受性,总结抑郁症的神经生物学,回顾氯胺酮快速抗抑郁作用的潜在机制,并讨论新一代速效抗抑郁药的前景。