Gerhard Danielle M, Duman Ronald S
Department of Psychiatry, Laboratory of Molecular Psychiatry, Yale University School of Medicine, New Haven, CT 06508, USA.
Curr Behav Neurosci Rep. 2018 Mar;5(1):36-47. Epub 2018 Feb 5.
Ketamine produces rapid (within hours) antidepressant actions, even in patients considered treatment resistant, and even shows promise for suicidal ideation. Here, we review current research on the molecular and cellular mechanisms of ketamine and other novel rapid-acting antidepressants, and briefly explore gender differences in the pathophysiology and treatment of MDD.
Ketamine, an NMDA receptor antagonist, increases BDNF release and synaptic connectivity, opposing the deficits caused by chronic stress and depression. Efforts are focused on the development of novel rapid agents that produce similar synaptic and rapid antidepressant actions, but without the side effects of ketamine. The impact of gender on the response to ketamine and other rapid-acting antidepressants is in early stages of investigation.
The discovery that ketamine produces rapid therapeutic actions for depression and suicidal ideation represents a major breakthrough and much needed alternative to currently available medications. However, novel fast acting agents with fewer side effects are needed, as well as elucidation of the efficacy of these rapid-acting antidepressants for depression in women.
氯胺酮能产生快速（数小时内）抗抑郁作用，即使对难治性患者也是如此，甚至对自杀观念也显示出前景。在此，我们综述了目前关于氯胺酮及其他新型速效抗抑郁药的分子和细胞机制的研究，并简要探讨了重度抑郁症病理生理学和治疗中的性别差异。
氯胺酮作为一种N-甲基-D-天冬氨酸（NMDA）受体拮抗剂，可增加脑源性神经营养因子（BDNF）释放和突触连接，对抗慢性应激和抑郁造成的缺陷。目前的研究重点是开发能产生类似突触和快速抗抑郁作用，但无氯胺酮副作用的新型速效药物。性别对氯胺酮及其他速效抗抑郁药反应的影响尚处于研究初期。
氯胺酮对抑郁症和自杀观念具有快速治疗作用这一发现是一项重大突破，也是现有药物急需的替代方法。然而，需要有副作用更少的新型速效药物，同时也需要阐明这些速效抗抑郁药对女性抑郁症的疗效。
