Several studies have demonstrated the effectiveness of ketamine in rapidly alleviating depression and suicidal ideation. Intense research efforts have been undertaken to expose the precise mechanism underlying the antidepressant action of ketamine; however, the translation of findings into new clinical treatments has been slow. This translational gap is partially explained by a lack of understanding of the function of time and circadian timing in the complex neurobiology around ketamine. Indeed, the acute pharmacological effects of a single ketamine treatment last for only a few hours, whereas the antidepressant effects peak at around 24 h and are sustained for the following few days. Numerous studies have investigated the acute and long-lasting neurobiological changes induced by ketamine; however, the most dramatic and fundamental change that the brain undergoes each day is rarely taken into consideration. Here, we explore the link between sleep and circadian regulation and rapid-acting antidepressant effects and summarize how diverse phenomena associated with ketamine's antidepressant actions – such as cortical excitation, synaptogenesis, and involved molecular determinants – are intimately connected with the neurobiology of wake, sleep, and circadian rhythms. We review several recently proposed hypotheses about rapid antidepressant actions, which focus on sleep or circadian regulation, and discuss their implications for ongoing research. Considering these aspects may be the last piece of the puzzle necessary to gain a more comprehensive understanding of the effects of rapid-acting antidepressants on the brain.

几项研究已经证明氯胺酮在迅速缓解抑郁症和自杀意念方面的有效性。为了揭示氯胺酮抗抑郁作用的确切机制，已经进行了大量的研究工作；然而，将研究结果转化为新的临床治疗的速度很慢。这种翻译差距的部分原因是对氯胺酮周围复杂神经生物学中时间和昼夜节律的功能缺乏了解。事实上，单次氯胺酮治疗的急性药理作用仅持续几个小时，而抗抑郁作用在 24 小时左右达到峰值并持续数天。许多研究调查了氯胺酮引起的急性和持久的神经生物学变化。然而，大脑每天所经历的最剧烈和最根本的变化很少被考虑在内。在这里，我们探讨了睡眠与昼夜节律调节和速效抗抑郁作用之间的联系，并总结了与氯胺酮抗抑郁作用相关的各种现象——如皮质兴奋、突触发生和相​​关分子决定因素——与唤醒、睡眠的神经生物学密切相关。和昼夜节律。我们回顾了最近提出的几个关于快速抗抑郁作用的假设，这些假设侧重于睡眠或昼夜节律调节，并讨论它们对正在进行的研究的影响。考虑到这些方面可能是更全面地了解速效抗抑郁药对大脑的影响所必需的最后一块拼图。