Diazgranados Nancy, Ibrahim Lobna, Brutsche Nancy E, Newberg Andrew, Kronstein Phillip, Khalife Sami, Kammerer William A, Quezado Zenaide, Luckenbaugh David A, Salvadore Giacomo, Machado-Vieira Rodrigo, Manji Husseini K, Zarate Carlos A
Experimental Therapeutics, Mood and Anxiety Disorders Program, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA.
Arch Gen Psychiatry. 2010 Aug;67(8):793-802. doi: 10.1001/archgenpsychiatry.2010.90.
Existing therapies for bipolar depression have a considerable lag of onset of action. Pharmacological strategies that produce rapid antidepressant effects-for instance, within a few hours or days-would have an enormous impact on patient care and public health.
To determine whether an N-methyl-D-aspartate-receptor antagonist produces rapid antidepressant effects in subjects with bipolar depression.
A randomized, placebo-controlled, double-blind, crossover, add-on study conducted from October 2006 to June 2009.
Mood Disorders Research Unit at the National Institute of Mental Health, Bethesda, Maryland. Patients Eighteen subjects with DSM-IV bipolar depression (treatment-resistant).
Subjects maintained at therapeutic levels of lithium or valproate received an intravenous infusion of either ketamine hydrochloride (0.5 mg/kg) or placebo on 2 test days 2 weeks apart. The Montgomery-Asberg Depression Rating Scale was used to rate subjects at baseline and at 40, 80, 110, and 230 minutes and on days 1, 2, 3, 7, 10, and 14 postinfusion.
Change in Montgomery-Asberg Depression Rating Scale primary efficacy measure scores.
Within 40 minutes, depressive symptoms significantly improved in subjects receiving ketamine compared with placebo (d = 0.52, 95% confidence interval [CI], 0.28-0.76); this improvement remained significant through day 3. The drug difference effect size was largest at day 2 (d = 0.80, 95% CI, 0.55-1.04). Seventy-one percent of subjects responded to ketamine and 6% responded to placebo at some point during the trial. One subject receiving ketamine and 1 receiving placebo developed manic symptoms. Ketamine was generally well tolerated; the most common adverse effect was dissociative symptoms, only at the 40-minute point.
In patients with treatment-resistant bipolar depression, robust and rapid antidepressant effects resulted from a single intravenous dose of an N-methyl-D-aspartate antagonist.
双相抑郁症的现有疗法起效时间相当滞后。能产生快速抗抑郁效果的药理学策略——比如在数小时或数天内起效——将对患者护理和公共卫生产生巨大影响。
确定N-甲基-D-天冬氨酸受体拮抗剂对双相抑郁症患者是否有快速抗抑郁效果。
2006年10月至2009年6月进行的一项随机、安慰剂对照、双盲、交叉、附加研究。
马里兰州贝塞斯达国家心理健康研究所情绪障碍研究室。患者18名符合《精神疾病诊断与统计手册》第四版（DSM-IV）标准的双相抑郁症（难治性）患者。
维持在锂盐或丙戊酸盐治疗水平的受试者在间隔2周的2个试验日接受盐酸氯胺酮（0.5mg/kg）或安慰剂静脉输注。使用蒙哥马利-艾斯伯格抑郁评定量表在基线以及输注后40、80、110和230分钟以及第1、2、3、7、10和14天对受试者进行评分。
蒙哥马利-艾斯伯格抑郁评定量表主要疗效指标评分的变化。
与安慰剂相比，接受氯胺酮的受试者在40分钟内抑郁症状显著改善（d = 0.52，95%置信区间[CI]，0.28 - 0.76）；这种改善在第3天一直保持显著。药物差异效应量在第2天最大（d = 0.80，95%CI，0.55 - 1.04）。在试验期间的某个时间点，71%的受试者对氯胺酮有反应，6%的受试者对安慰剂有反应。1名接受氯胺酮的受试者和1名接受安慰剂的受试者出现躁狂症状。氯胺酮总体耐受性良好；最常见的不良反应是分离性症状，仅在40分钟时出现。
在难治性双相抑郁症患者中，单次静脉注射N-甲基-D-天冬氨酸拮抗剂可产生强烈且快速的抗抑郁效果。
