Derakhshanian Sahar, Zhou Maxine, Rath Alexander, Barlow Rachel, Bertrand Sarah, DeGraw Caroline, Lee Christopher, Hasoon Jamal, Kaye Alan D
Department of Psychiatry, Louisiana State University Shreveport, LA.
Louisiana State University Health Sciences Center Shreveport School of Medicine, LA.
Health Psychol Res. 2021 Jun 22;9(1):25091. doi: 10.52965/001c.25091. eCollection 2021.
This is a comprehensive review of the literature regarding the use of ketamine as a treatment for treatment-resistant depression (TRD). It covers the epidemiology, risk factors, pathophysiology, and current treatment modalities regarding Major Depressive Disorder (MDD) and TRD. It provides background on the mechanism of action of ketamine, its history, current approved and off-label indications in the field of psychiatry, and then provides an overview of the existing evidence for the use of ketamine in the treatment of TRD.
MDD is a mental illness that puts an enormous strain on the affected and a high socio-economic burden on society. The illness is complex and combines genetic, pathophysiologic, and environmental factors that combine to negatively affect neurotransmitter balance in the brain. Additional evidence suggests dysregulation of the hypothalamic-pituitary (HPA) axis, brain-derived neurotrophic factor (BDNF), vitamin D levels, and involvement of pro-inflammatory markers. Core symptoms include depressed mood or anhedonia, combined with neurovegetative symptoms such as sleep impairment, changes in appetite, feelings of worthlessness and guilt, and psychomotor retardation. Current first-line treatment options are antidepressants of the selective serotonin reuptake inhibitor (SSRI) and serotonin-norepinephrine reuptake inhibitor (SNRI) class. Failure to respond to two adequate trials of treatment meets the criteria for TRD. Esketamine (Spravato) is an NMDA-receptor antagonist with additional AMPA-receptor agonist properties, which the FDA approved in 2019 to treat adult TRD in conjunction with an oral antidepressant. It can be administered intranasally, providing a rapid response and proven effective and safe. Additional research suggests that oral ketamine might be effective for PTSD and anxiety disorders. Intravenous administration of ketamine has also shown benefits for acute suicidal ideation and depression and substance use to reduce relapse rates.
TRD is associated with huge costs on individual and societal levels. Underlying disease processes are multifactorial and not well understood. Adjunctive therapies for TRD with proven benefits exist, but acutely depressed and suicidal patients often require prolonged inpatient stabilization. Intranasal esketamine is a new FDA-approved alternative with rapid benefit for TRD, which has also shown a rapid reduction in suicidal ideation while maintaining a favorable side-effect profile. Additional potential off-label uses for ketamine in psychiatric disorders have been studied, including PTSD, anxiety disorders, bipolar depression, and substance use disorders.
本文是一篇关于使用氯胺酮治疗难治性抑郁症（TRD）的文献综述。它涵盖了重度抑郁症（MDD）和TRD的流行病学、危险因素、病理生理学以及当前的治疗方式。它提供了氯胺酮作用机制的背景信息、其历史、目前在精神病学领域已获批和未获批的适应症，然后概述了使用氯胺酮治疗TRD的现有证据。
MDD是一种给患者带来巨大压力且给社会造成高昂社会经济负担的精神疾病。这种疾病很复杂，是遗传、病理生理和环境因素共同作用的结果，这些因素共同对大脑中的神经递质平衡产生负面影响。更多证据表明下丘脑 - 垂体（HPA）轴失调、脑源性神经营养因子（BDNF）、维生素D水平以及促炎标志物的参与。核心症状包括情绪低落或快感缺失，同时伴有诸如睡眠障碍、食欲改变、无价值感和内疚感以及精神运动迟缓等神经植物性症状。目前的一线治疗选择是选择性5-羟色胺再摄取抑制剂（SSRI）和5-羟色胺 - 去甲肾上腺素再摄取抑制剂（SNRI）类的抗抑郁药。对两次充分治疗试验均无反应符合TRD的标准。艾氯胺酮（Spravato）是一种具有额外AMPA受体激动剂特性的NMDA受体拮抗剂，美国食品药品监督管理局（FDA）于2019年批准其与口服抗抑郁药联合用于治疗成人TRD。它可以通过鼻内给药，起效迅速且已证明有效和安全。更多研究表明口服氯胺酮可能对创伤后应激障碍（PTSD）和焦虑症有效。静脉注射氯胺酮对急性自杀意念和抑郁症以及物质使用以降低复发率也显示出益处。
TRD在个人和社会层面都与巨大成本相关。潜在疾病过程是多因素的且尚未完全了解。存在已证明有益的TRD辅助治疗方法，但急性抑郁和有自杀倾向的患者通常需要长时间住院稳定病情。鼻内艾氯胺酮是FDA新批准的一种对TRD有快速疗效的药物，它在维持良好副作用特征的同时也显示出自杀意念迅速减少。氯胺酮在精神疾病中的其他潜在未获批用途也已得到研究，包括PTSD、焦虑症、双相抑郁症和物质使用障碍。
