Yavi Mani, Lee Holim, Henter Ioline D, Park Lawrence T, Zarate Carlos A
Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health [NIMH-NIH], 10 Center Dr, Room 7-5545, Bethesda, MD 20814 USA.
Discov Ment Health. 2022;2(1):9. doi: 10.1007/s44192-022-00012-3. Epub 2022 Apr 15.
This manuscript reviews the clinical evidence regarding single-dose intravenous (IV) administration of the novel glutamatergic modulator racemic ()-ketamine (hereafter referred to as ketamine) as well as its -enantiomer, intranasal esketamine, for the treatment of major depressive disorder (MDD). Initial studies found that a single subanesthetic-dose IV ketamine infusion rapidly (within one day) improved depressive symptoms in individuals with MDD and bipolar depression, with antidepressant effects lasting three to seven days. In 2019, esketamine received FDA approval as an adjunctive treatment for treatment-resistant depression (TRD) in adults. Esketamine was approved under a risk evaluation and mitigation strategy (REMS) that requires administration under medical supervision. Both ketamine and esketamine are currently viable treatment options for TRD that offer the possibility of rapid symptom improvement. The manuscript also reviews ketamine's use in other psychiatric diagnoses-including suicidality, obsessive-compulsive disorder, post-traumatic stress disorder, substance abuse, and social anxiety disorder-and its potential adverse effects. Despite limited data, side effects for antidepressant-dose ketamine-including dissociative symptoms, hypertension, and confusion/agitation-appear to be tolerable and limited to around the time of treatment. Relatively little is known about ketamine's longer-term effects, including increased risks of abuse and/or dependence. Attempts to prolong ketamine's effects with combined therapy or a repeat-dose strategy are also reviewed, as are current guidelines for its clinical use. In addition to presenting a novel and valuable treatment option, studying ketamine also has the potential to transform our understanding of the mechanisms underlying mood disorders and the development of novel therapeutics.
本手稿回顾了有关新型谷氨酸能调节剂外消旋（）-氯胺酮（以下简称氯胺酮）及其S-对映体艾氯胺酮鼻内给药治疗重度抑郁症（MDD）的单剂量静脉注射（IV）的临床证据。初步研究发现，单剂量亚麻醉剂量的静脉注射氯胺酮能迅速（在一天内）改善MDD和双相抑郁症患者的抑郁症状，抗抑郁作用持续三至七天。2019年，艾氯胺酮获得美国食品药品监督管理局（FDA）批准，作为成人难治性抑郁症（TRD）的辅助治疗药物。艾氯胺酮是根据风险评估和缓解策略（REMS）获批的，该策略要求在医疗监督下给药。氯胺酮和艾氯胺酮目前都是TRD的可行治疗选择，都有可能迅速改善症状。该手稿还回顾了氯胺酮在其他精神疾病诊断中的应用，包括自杀倾向、强迫症、创伤后应激障碍、药物滥用和社交焦虑症，以及其潜在的不良反应。尽管数据有限，但抗抑郁剂量氯胺酮的副作用，包括解离症状、高血压和意识模糊/激动，似乎是可以耐受的，并且仅限于治疗期间。关于氯胺酮的长期影响，包括滥用和/或依赖风险增加，人们了解得相对较少。还回顾了通过联合治疗或重复给药策略延长氯胺酮作用的尝试，以及其临床使用的现行指南。除了提供一种新颖且有价值的治疗选择外，对氯胺酮的研究还有可能改变我们对情绪障碍潜在机制的理解以及新型治疗方法的开发。
