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Ketamine as a Fast Acting Antidepressant: Current Knowledge and Open Questions

机译：氯胺酮作为速效抗抑郁药：当前知识和未解决的问题

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Summary Several recent studies have shown that a single intravenous subanesthetic dose of ketamine, a NMDA receptor antagonist, exerts rapid antidepressant effects in patients with treatment refractory mood disorders and reduces suicidal ideation. Those insights have fueled tremendous excitement in the efforts to elucidate the mechanism underlying ketamine's antidepressant properties in animal models of depression, as well as in humans through the use of brain imaging as well as peripheral blood measurements. For example, there is emerging evidence that ketamine's antidepressant properties rely on increasing AMPA signaling and rapidly inducing synaptogenesis. While pilot clinical studies are promising, a number of critical questions still remain unanswered. They relate to the safe and effective use of ketamine in patients with mood disorders regarding the optimal dose range, modality and method of administration for acute and long‐term maintenance of effect, and the biomarkers associated with responseonresponse. In this review article, we first summarize the clinical evidence about the use of ketamine in mood disorders, as well as preclinical and humans studies which investigated the mechanisms of action of ketamine, and predictors of antidepressant response in clinical populations. We then provide a critical overview of the knowledge gaps about the use of ketamine in depression and suggest some future research directions for the investigation of ketamine as a promising tool to develop novel more effective and fast acting antidepressants.
机译：总结最近的一些研究表明，单次静脉麻醉剂量的氯胺酮（一种NMDA受体拮抗剂）可在治疗难治性情绪障碍患者中发挥快速的抗抑郁作用，并减少自杀意念。通过使用脑成像以及外周血测量结果，这些努力为阐明氯胺酮在抑郁症动物模型以及人类中的抗抑郁特性的机理提供了极大的兴奋。例如，越来越多的证据表明，氯胺酮的抗抑郁特性依赖于增加的AMPA信号传导并迅速诱导突触发生。尽管试点临床研究前景广阔，但许多关键问题仍未得到解答。它们涉及在情绪障碍患者中安全有效地使用氯胺酮，涉及急性和长期维持疗效的最佳剂量范围，方式和给药方法，以及与反应/无反应相关的生物标志物。在这篇综述文章中，我们首先总结了有关氯胺酮在情绪障碍中使用的临床证据，以及临床前和人体研究，这些研究调查了氯胺酮的作用机理以及临床人群中抗抑郁反应的预测因子。然后，我们提供了有关在抑郁症中使用氯胺酮的知识空白的重要概述，并为氯胺酮作为开发新型更有效和速效抗抑郁药的有前途的工具提供了一些未来的研究方向。

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