Murrough James W, Wan Le-Ben, Iacoviello Brian, Collins Katherine A, Solon Carly, Glicksberg Benjamin, Perez Andrew M, Mathew Sanjay J, Charney Dennis S, Iosifescu Dan V, Burdick Katherine E
Mood and Anxiety Disorders Program, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1230, New York, NY, 10029, USA,
Psychopharmacology (Berl). 2013 Sep 11. doi: 10.1007/s00213-013-3255-x.
The N-methyl-D-aspartate (NMDA) glutamate receptor antagonist ketamine has demonstrated rapid antidepressant effects in patients with treatment-resistant depression (TRD). Despite the promise of a novel and urgently needed treatment for refractory depression, concerns regarding potential adverse neurocognitive effects of ketamine remain.
Although extensive research has been conducted in healthy volunteers, there is a paucity of studies examining the neurocognitive effects of ketamine in depressed patients. Therefore, the aims of the current study were to characterize the relationship between baseline neurocognition and antidepressant response to ketamine, measure the acute impact of ketamine on neurocognition, and investigate the relationship between acute neurocognitive effects of ketamine and antidepressant response.
Neurocognitive functioning was assessed in 25 patients with TRD using a comprehensive battery: estimated premorbid intelligence quotient (IQ), current IQ, and tests from the MATRICS Consensus Cognitive Battery (MCCB). A subset of the MCCB was repeated immediately following a 40-min intravenous infusion of ketamine (0.5 mg/kg).
Patients who responded to ketamine 24 h following treatment had poorer baseline neurocognitive performance relative to nonresponders and, in particular, slower processing speed (F = 8.42; df = 23; p = 0.008). Ketamine was associated with selective impairments in memory recall, and the degree of cognitive change carried negative prognostic significance (e.g., negative cognitive effects immediately after ketamine predicted lower response rate at 24 h; Fisher's exact test two-sided p = 0.027).
Taken together, our findings suggest a potential baseline neurocognitive predictor of ketamine response and an inverse relationship between the cognitive effects of ketamine and antidepressant efficacy.
N-甲基-D-天冬氨酸（NMDA）谷氨酸受体拮抗剂氯胺酮已在难治性抑郁症（TRD）患者中显示出快速抗抑郁作用。尽管氯胺酮有望成为一种治疗难治性抑郁症的新型且急需的疗法，但对其潜在的不良神经认知效应仍存在担忧。
尽管已在健康志愿者中进行了广泛研究，但针对氯胺酮对抑郁症患者神经认知效应的研究却很少。因此，本研究的目的是确定基线神经认知与氯胺酮抗抑郁反应之间的关系，测量氯胺酮对神经认知的急性影响，并研究氯胺酮的急性神经认知效应与抗抑郁反应之间的关系。
使用一套综合测试对25例TRD患者的神经认知功能进行评估：估计病前智商（IQ）、当前智商以及来自精神分裂症认知功能成套测验共识认知电池（MCCB）的测试。在静脉输注氯胺酮（0.5mg/kg）40分钟后，立即重复进行MCCB的一部分测试。
治疗后24小时对氯胺酮有反应的患者，其基线神经认知表现相对于无反应者较差，尤其是处理速度较慢（F = 8.42；自由度 = 23；p = 0.008）。氯胺酮与记忆回忆的选择性损害有关，认知变化程度具有负面预后意义（例如，氯胺酮给药后立即出现的负面认知效应预示着24小时时的反应率较低；Fisher精确检验双侧p = 0.027）。
综上所述，我们的研究结果表明，存在一个潜在的氯胺酮反应基线神经认知预测指标，且氯胺酮的认知效应与抗抑郁疗效之间呈负相关。
