Nearly 5% of individuals in the USA had serious thoughts of suicide in 2019 and over 30% of individuals suffering with major depressive disorder reported suicidal ideation with 2 million of those reporting suicidal ideation with some level of intent. However, options to treat depressed individuals considered at imminent risk of suicide remain limited. Until the recent approval of esketamine in the treatment of patients with major depressive disorder with serious suicidal thoughts or actions, no medications had been specifically evaluated for use in this population in the acute setting. This review discusses the history and the current understanding of the role of ketamine and esketamine in depression and suicidal ideation and behavior. It covers some of the pivotal studies in this field and provides a summary of their major findings. The trials of esketamine in patients with major depressive disorder with active suicidal ideation or behavior are the first large-scale trials in patients considered at imminent risk of suicide. As such, the design of these studies is by definition novel, a fact that complicates the interpretation of the data and assessment of the true clinical meaningfulness of the findings. Despite this, the findings in toto draw a consistent picture of benefits that appears to outweigh the potential risks of the treatment. The studies also serve to highlight the complexities and limitations associated with clinical trials aiming to test the ability of novel therapeutics to reduce the burden and risks in patients with suicide ideation and behavior.

2019 年，美国近 5% 的人曾有过严重的自杀念头，超过 30% 的重度抑郁症患者报告有自杀念头，其中 200 万人报告有某种程度的自杀念头。然而，治疗被认为有迫在眉睫自杀风险的抑郁症患者的选择仍然有限。直到最近批准艾氯胺酮用于治疗有严重自杀念头或行为的重度抑郁症患者之前，还没有专门评估过在急性环境中用于该人群的药物。这篇综述讨论了氯胺酮和艾氯胺酮在抑郁症和自杀意念和行为中的作用的历史和当前理解。它涵盖了该领域的一些关键研究，并总结了他们的主要发现。在有积极自杀意念或行为的重度抑郁症患者中进行的艾氯胺酮试验是第一次在被认为有即将自杀风险的患者中进行的大规模试验。因此，这些研究的设计从定义上讲是新颖的，这一事实使数据的解释和对研究结果的真正临床意义的评估变得复杂。尽管如此，研究结果还是一致地描绘了似乎超过治疗的潜在风险的益处。这些研究还有助于强调与临床试验相关的复杂性和局限性，旨在测试新疗法在减轻有自杀意念和行为的患者的负担和风险方面的能力。