Abdallah Chadi G, Adams Thomas G, Kelmendi Benjamin, Esterlis Irina, Sanacora Gerard, Krystal John H
Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut.
Clinical Neuroscience Division, Department of Veterans Affairs, National Center for Posttraumatic Stress Disorder, Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut.
Depress Anxiety. 2016 Aug;33(8):689-97. doi: 10.1002/da.22501. Epub 2016 Apr 6.
Major depressive disorder (MDD) is a common and debilitating psychiatric disorder. Traditional antidepressants are of limited efficacy and take weeks to months to yield full therapeutic effects. Thus, there is a clear need for effective rapid-acting antidepressant medications. The N-methyl-d-aspartate receptor (NMDA-R) antagonist, ketamine, has received a great deal of attention over the last 20 years due to the discovery that a single subanesthetic dose leads to a rapid antidepressant effect in individuals with treatment-resistant depression. Animal and human research suggest that ketamine's antidepressant effects are mediated by a glutamate surge that leads to a cascade of events that result in synaptogenesis and reversal of the negative effects of chronic stress and depression, particularly within the prefrontal cortex (PFC). Preclinical and clinical data have provided compelling insights into the mechanisms underlying the rapid-acting antidepressant effects of ketamine. This review discusses stress-related neurobiology of depression and the safety, tolerability, and efficacy of ketamine for MDD, along with a review of ketamine's mechanism of action and prospective predictors of treatment response. Research limitations and future clinical prospects are also discussed.
重度抑郁症（MDD）是一种常见且使人衰弱的精神疾病。传统抗抑郁药疗效有限，需要数周甚至数月才能产生充分的治疗效果。因此，显然需要有效的速效抗抑郁药物。N-甲基-D-天冬氨酸受体（NMDA-R）拮抗剂氯胺酮在过去20年中受到了广泛关注，因为人们发现单次亚麻醉剂量的氯胺酮可使难治性抑郁症患者产生快速抗抑郁作用。动物和人体研究表明，氯胺酮的抗抑郁作用是由谷氨酸激增介导的，这会引发一系列事件，导致突触形成，并逆转慢性应激和抑郁症的负面影响，尤其是在前额叶皮质（PFC）内。临床前和临床数据为氯胺酮速效抗抑郁作用的潜在机制提供了令人信服的见解。本文综述了抑郁症与应激相关的神经生物学，以及氯胺酮治疗MDD的安全性、耐受性和疗效，并对氯胺酮的作用机制和治疗反应的前瞻性预测指标进行了综述。还讨论了研究局限性和未来的临床前景。
