Vutskits Laszlo
From the Department of Anesthesiology, Pharmacology and Intensive Care, University Hospitals of Geneva, Geneva, Switzerland.
Anesth Analg. 2018 Jan;126(1):208-216. doi: 10.1213/ANE.0000000000002594.
Major depressive disorder is a frequent and devastating psychological condition with tremendous public health impact. The underlying pathophysiological mechanisms involve abnormal neurotransmission and a relatedly impaired synaptic plasticity. Since general anesthetics are potent modulators of neuronal activity and, thereby, can exert long-term context-dependent impact on neural networks, an intriguing hypothesis is that these drugs could enhance impaired neural plasticity associated with certain psychiatric diseases. Clinical observations over the past few decades appear to confirm this possibility. Indeed, equipotency of general anesthesia alone in comparison with electroconvulsive therapy under general anesthesia has been demonstrated in several clinical trials. Importantly, in the past 15 years, intravenous administration of subanesthetic doses of ketamine have also been demonstrated to have rapid antidepressant effects. The molecular, cellular, and network mechanisms underlying these therapeutic effects have been partially identified. Although several important questions remain to be addressed, the ensemble of these experimental and clinical observations opens new therapeutic possibilities in the treatment of depressive disorders. Importantly, they also suggest a new therapeutic role for anesthetics that goes beyond their principal use in the perioperative period to facilitate surgery.
重度抑郁症是一种常见且具有毁灭性的心理疾病，对公众健康有巨大影响。其潜在的病理生理机制涉及神经传递异常以及相关的突触可塑性受损。由于全身麻醉药是神经元活动的强效调节剂，因此能够对神经网络产生长期的、依赖于环境的影响，一个有趣的假说是，这些药物可以增强与某些精神疾病相关的受损神经可塑性。过去几十年的临床观察似乎证实了这种可能性。事实上，在多项临床试验中已证明，单纯全身麻醉与全身麻醉下的电休克治疗具有等效性。重要的是，在过去15年中，静脉注射亚麻醉剂量的氯胺酮也已被证明具有快速抗抑郁作用。这些治疗效果背后的分子、细胞和网络机制已部分得到确定。尽管仍有几个重要问题有待解决，但这些实验和临床观察结果为抑郁症的治疗开辟了新的治疗可能性。重要的是，它们还表明麻醉药具有一种新的治疗作用，这种作用超出了其在围手术期促进手术的主要用途。
