Experimental Therapeutics & Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, and Department of Health and Human Services, Bethesda, Maryland, USA.
Biol Psychiatry. 2012 Jun 1;71(11):939-46. doi: 10.1016/j.biopsych.2011.12.010. Epub 2012 Jan 31.
Currently, no pharmacological treatments for bipolar depression exist that exert rapid (within hours) antidepressant or antisuicidal effects. We previously reported that intravenous administration of the N-methyl-D-aspartate antagonist ketamine produced rapid antidepressant effects in patients with treatment-resistant bipolar depression. The present study sought to replicate this finding in an independent sample.
In this double-blind, randomized, crossover, placebo-controlled study, 15 subjects with DSM-IV bipolar I or II depression maintained on therapeutic levels of lithium or valproate received a single intravenous infusion of either ketamine hydrochloride (.5 mg/kg) or placebo on 2 test days 2 weeks apart. The primary outcome measure was the Montgomery-Asberg Depression Rating Scale, which was used to rate overall depressive symptoms at baseline; at 40, 80, 110, and 230 minutes postinfusion; and on days 1, 2, 3, 7, 10, and 14 postinfusion.
Within 40 minutes, depressive symptoms, as well as suicidal ideation, significantly improved in subjects receiving ketamine compared with placebo (d = .89, 95% confidence interval = .61-1.16, and .98, 95% confidence interval = .64-1.33, respectively); this improvement remained significant through day 3. Seventy-nine percent of subjects responded to ketamine and 0% responded to placebo at some point during the trial. The most common side effect was dissociative symptoms, which occurred only at the 40-minute time point.
This study replicated our previous finding that patients with bipolar depression who received a single ketamine infusion experienced a rapid and robust antidepressant response. In addition, we found that ketamine rapidly improved suicidal ideation in these patients.
目前，尚无具有快速（数小时内）抗抑郁或抗自杀作用的双相抑郁症的药物治疗方法。我们之前报道过，静脉注射 N-甲基-D-天冬氨酸拮抗剂氯胺酮可使治疗抵抗性双相抑郁症患者迅速产生抗抑郁作用。本研究旨在独立样本中复制这一发现。
在这项双盲、随机、交叉、安慰剂对照研究中，15 名符合 DSM-IV 双相 I 或 II 型抑郁症标准、锂或丙戊酸维持治疗剂量的患者，在相隔 2 周的 2 个测试日接受单剂量氯胺酮盐酸盐（0.5mg/kg）或安慰剂静脉输注。主要观察指标是蒙哥马利-阿斯伯格抑郁评定量表（MADRS），用于评定基线时的总体抑郁症状；在输注后 40、80、110 和 230 分钟；以及输注后第 1、2、3、7、10 和 14 天。
接受氯胺酮治疗的患者在 40 分钟内，抑郁症状以及自杀意念明显改善，与安慰剂相比（d =.89，95%置信区间为.61-1.16，和.98，95%置信区间为.64-1.33）；这种改善在第 3 天仍保持显著。79%的患者在试验过程中的某个时间点对氯胺酮有反应，而对安慰剂没有反应。最常见的副作用是分离症状，仅在 40 分钟时出现。
本研究复制了我们之前的发现，即接受单次氯胺酮输注的双相抑郁症患者迅速产生了强烈的抗抑郁反应。此外，我们发现氯胺酮可迅速改善这些患者的自杀意念。
