Phelps Laura E, Brutsche Nancy, Moral Jazmin R, Luckenbaugh David A, Manji Husseini K, Zarate Carlos A
Laboratory of Molecular Pathophysiology and Experimental Therapeutics, Mood and Anxiety Disorders Program, National Institute of Mental Health, National Institutes of Health/DHHS, 10 Center Drive, Bethesda, MD 20892-1282, USA.
Biol Psychiatry. 2009 Jan 15;65(2):181-4. doi: 10.1016/j.biopsych.2008.09.029. Epub 2008 Nov 8.
A high rate of comorbidity exists between mood disorders and alcohol dependence. Furthermore, both ketamine, a dissociative anesthetic with a recently described rapid-onset antidepressant effect, and ethanol are N-methyl-D-aspartate (NMDA) receptor antagonists. Previous investigations of healthy individuals with a family history of alcohol dependence have found that these individuals have an attenuated response to ketamine's perceptual disturbance and dysphoric effects similar to that found in individuals with a self-reported history of alcohol dependence. This study investigated whether a family history of alcohol dependence influences ketamine's initial antidepressant effect.
Twenty-six subjects with DSM-IV treatment-resistant major depression were given an open-label intravenous infusion of ketamine hydrochloride (.5 mg/kg) and rated using various depression scales at baseline, 40, 80, 120, and 230 min postinfusion. The primary outcome measure was Montgomery-Asberg Depression Rating Scale (MADRS) scores.
Subjects with a family history of alcohol dependence showed significantly greater improvement in MADRS scores compared with subjects who had no family history of alcohol dependence.
A family history of alcohol dependence appears to predict a rapid initial antidepressant response to an NMDA receptor antagonist.
情绪障碍与酒精依赖之间存在高共病率。此外，氯胺酮（一种具有近期描述的快速起效抗抑郁作用的解离麻醉剂）和乙醇都是N-甲基-D-天冬氨酸（NMDA）受体拮抗剂。先前对有酒精依赖家族史的健康个体的研究发现，这些个体对氯胺酮的知觉障碍和烦躁不安效应的反应减弱，类似于有自我报告酒精依赖史的个体。本研究调查了酒精依赖家族史是否会影响氯胺酮的初始抗抑郁作用。
对26名患有DSM-IV难治性重度抑郁症的受试者进行开放标签静脉输注盐酸氯胺酮（0.5mg/kg），并在输注前、输注后40、80、120和230分钟使用各种抑郁量表进行评分。主要结局指标是蒙哥马利-阿斯伯格抑郁评定量表（MADRS）评分。
与无酒精依赖家族史的受试者相比，有酒精依赖家族史的受试者MADRS评分改善更为显著。
酒精依赖家族史似乎预示着对NMDA受体拮抗剂的快速初始抗抑郁反应。
