Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, Washington, USA.
Curr Opin Anaesthesiol. 2021 Oct 1;34(5):556-562. doi: 10.1097/ACO.0000000000001039.
The antidepressant effect of subanesthetic doses of ketamine was recognized 20 years ago. This review briefly summarizes the current understanding of the antidepressant mechanisms and the available clinical research on the use of racemic ketamine and enantiomer esketamine for depression.
The antidepressant effect of subanesthetic doses of ketamine is currently considered to be predominantly mediated by improved neuroplasticity in cortico-limbic areas in the brain. Single dose of 0.5 mg/kg of ketamine infused intravenously over 40 min, or single intranasal dose of esketamine cause rapid antidepressant and antisuicidal effects within hours of administration, and the antidepressant effect may last up to a week. Repeated administration of nasal spray esketamine is considered to prevent relapse of depression. Longitudinal studies are currently insufficient. When used in various doses for anesthetic induction for electroconvulsive therapy, ketamine improves seizure quality and may possibly diminish posttherapy cognitive impairment.
A rapid onset antidepressive effect of ketamine and esketamine has been proven conclusively. The results of extensive basic science research of the mechanism of action of low-dose ketamine doses has led to an alternative hypothesis of the pathophysiology of depression and the development of a novel neurotrophic concept of depression. Further longitudinal studies are warranted to determine the safety and efficacy of repeated administration of ketamine and its analogs to prevent relapse and recurrence of depression.
亚麻醉剂量的氯胺酮的抗抑郁作用在 20 年前就已被认识到。本文简要总结了目前对氯胺酮抗抑郁机制的理解，以及使用外消旋氯胺酮和对映体右美沙芬治疗抑郁症的现有临床研究。
目前认为亚麻醉剂量的氯胺酮的抗抑郁作用主要是通过改善大脑皮质边缘区的神经可塑性来介导的。静脉输注 0.5mg/kg 的氯胺酮，持续 40 分钟，或单次鼻内给予右美沙芬，可在给药后数小时内迅速产生抗抑郁和抗自杀作用，抗抑郁作用可持续长达一周。鼻内喷雾右美沙芬的重复给药被认为可以预防抑郁症的复发。目前纵向研究还不够充分。在用于电惊厥治疗的麻醉诱导时，各种剂量的氯胺酮可改善癫痫发作质量，并可能减轻治疗后认知障碍。
氯胺酮和右美沙芬具有快速起效的抗抑郁作用，这一结论已得到证实。对低剂量氯胺酮作用机制的广泛基础科学研究的结果，导致了对抑郁症病理生理学的替代假说和对抑郁症的新型神经营养概念的发展。需要进一步的纵向研究来确定重复给予氯胺酮及其类似物预防抑郁症复发和复发的安全性和有效性。
