Saligan Leorey N, Luckenbaugh David A, Slonena Elizabeth E, Machado-Vieira Rodrigo, Zarate Carlos A
National Institute of Nursing Research, Division of Intramural Research, National Institutes of Health, 31 Center Drive, MSC 2178, Bethesda, MD 209892, USA.
Experimental Therapeutics & Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, 10 Center Drive, Rm 4N222, MSC 1381 Bethesda, MD 20892, USA.
J Affect Disord. 2016 Apr;194:115-9. doi: 10.1016/j.jad.2016.01.009. Epub 2016 Jan 19.
Fatigue is a multidimensional condition that is difficult to treat with standard monoaminergic antidepressants. Ketamine, an N-methyl-D-aspartate receptor (NMDAR) antagonist produces rapid and robust improvements in depressive symptoms in treatment-resistant depression. However, there is a dearth of literature examining the anti-fatigue effects of ketamine. We hypothesize that ketamine will rapidly improve fatigue symptoms in treatment-resistant depressed patients.
This is an exploratory analysis of data obtained from two double-blind, randomized, placebo-controlled, crossover trials. A total of 36 participants with treatment-resistant bipolar I or II disorder in a depressive episode (maintained on therapeutic levels of lithium or valproate) received a single infusion of ketamine hydrochloride intravenously (0.5 mg/kg over 40 min) or placebo. A post-hoc analysis compared fatigue scores on ketamine vs. placebo at 10 time points from baseline through 14 days post-treatment using the National Institute of Health-Brief Fatigue Inventory.
A linear mixed model showed that ketamine significantly lowered fatigue scores compared to placebo from 40 min post-treatment to Day 14 with the exception of Day 7. The largest difference in anti-fatigue effects between placebo and ketamine was at day 2 (d=0.58, p<0.05). The effect remained significant after controlling for changes in non-fatigue depressive symptoms.
The retrospective nature and a small sample size are study limitations.
Ketamine rapidly improved fatigue relative to placebo in a group of individuals with treatment-resistant bipolar depression. NMDAR is a glutamate receptor; hence, glutamate may represent a valuable target to study the clinical efficacy of new anti-fatigue approaches in multiple disorders.
疲劳是一种多维度状况，难以用标准的单胺能抗抑郁药进行治疗。氯胺酮作为一种N-甲基-D-天冬氨酸受体（NMDAR）拮抗剂，可使难治性抑郁症患者的抑郁症状迅速且显著改善。然而，关于氯胺酮抗疲劳作用的文献却很匮乏。我们推测氯胺酮能迅速改善难治性抑郁症患者的疲劳症状。
这是一项对来自两项双盲、随机、安慰剂对照、交叉试验的数据进行的探索性分析。共有36名处于抑郁发作期（维持在锂盐或丙戊酸盐治疗水平）的难治性双相I型或II型障碍患者，静脉注射单次氯胺酮盐酸盐（40分钟内注射0.5mg/kg）或安慰剂。一项事后分析使用美国国立卫生研究院简明疲劳量表，比较了从基线到治疗后14天的10个时间点上氯胺酮组与安慰剂组的疲劳评分。
线性混合模型显示，与安慰剂相比，从治疗后40分钟到第14天，氯胺酮显著降低了疲劳评分，但第7天除外。安慰剂和氯胺酮在抗疲劳作用上的最大差异出现在第2天（d = 0.58，p < 0.05）。在控制了非疲劳性抑郁症状的变化后，该效应仍然显著。
研究的回顾性性质和小样本量是研究的局限性。
在一组难治性双相抑郁症患者中，相对于安慰剂，氯胺酮能迅速改善疲劳症状。NMDAR是一种谷氨酸受体；因此，谷氨酸可能是研究多种疾病中新的抗疲劳方法临床疗效的一个有价值的靶点。
