Carboni Ezio, Carta Anna R, Carboni Elena, Novelli Antonello
Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy.
Unit of Paediatrics, ASST Cremona Maggiore Hospital, Cremona, Italy.
Front Neurosci. 2021 Apr 30;15:657714. doi: 10.3389/fnins.2021.657714. eCollection 2021.
Repurposing ketamine in the therapy of depression could well represent a breakthrough in understanding the etiology of depression. Ketamine was originally used as an anesthetic drug and later its use was extended to other therapeutic applications such as analgesia and the treatment of addiction. At the same time, the abuse of ketamine as a recreational drug has generated a concern for its psychotropic and potential long-term effects; nevertheless, its use as a fast acting antidepressant in treatment-resistant patients has boosted the interest in the mechanism of action both in psychiatry and in the wider area of neuroscience. This article provides a comprehensive overview of the actions of ketamine and intends to cover: (i) the evaluation of its clinical use in the treatment of depression and suicidal behavior; (ii) the potential use of ketamine in pediatrics; (iii) a description of its mechanism of action; (iv) the involvement of specific brain areas in producing antidepressant effects; (v) the potential interaction of ketamine with the hypothalamic-pituitary-adrenal axis; (vi) the effect of ketamine on neuronal transmission in the bed nucleus of stria terminalis and on its output; (vii) the evaluation of any gender-dependent effects of ketamine; (viii) the interaction of ketamine with the inflammatory processes involved in depression; (ix) the evaluation of the effects observed with single or repeated administration; (x) a description of any adverse or cognitive effects and its abuse potential. Finally, this review attempts to assess whether ketamine's use in depression can improve our knowledge of the etiopathology of depression and whether its therapeutic effect can be considered an actual cure for depression rather than a therapy merely aimed to control the symptoms of depression.
将氯胺酮重新用于抑郁症治疗很可能代表着在理解抑郁症病因方面的一项突破。氯胺酮最初用作麻醉药物，后来其用途扩展到其他治疗应用，如镇痛和成瘾治疗。与此同时，氯胺酮作为一种消遣性药物被滥用，引发了人们对其精神作用和潜在长期影响的担忧；然而，它在难治性患者中作为一种速效抗抑郁药的使用，激发了精神病学和更广泛神经科学领域对其作用机制的兴趣。本文全面概述了氯胺酮的作用，并打算涵盖：（i）评估其在抑郁症和自杀行为治疗中的临床应用；（ii）氯胺酮在儿科的潜在用途；（iii）描述其作用机制；（iv）特定脑区在产生抗抑郁作用中的参与情况；（v）氯胺酮与下丘脑 - 垂体 - 肾上腺轴的潜在相互作用；（vi）氯胺酮对终纹床核神经元传递及其输出的影响；（vii）评估氯胺酮的任何性别依赖性效应；（viii）氯胺酮与抑郁症相关炎症过程的相互作用；（ix）评估单次或重复给药所观察到的效果；（x）描述任何不良或认知效应及其滥用潜力。最后，本综述试图评估氯胺酮在抑郁症治疗中的使用是否能增进我们对抑郁症病因病理学的了解，以及其治疗效果是否可被视为对抑郁症的真正治愈，而非仅仅旨在控制抑郁症症状的一种疗法。
