A randomized add-on trial of an N-methyl-D-aspartate antagonist in treatment-resistant bipolar depression.
A randomized add-on trial of an N-methyl-D-aspartate antagonist in treatment-resistant bipolar depression.
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DOI：
10.1001/archgenpsychiatry.2010.90
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发表时间：
2010-08
影响因子：
--
通讯作者：
Zarate, Carlos A., Jr.
中科院分区：
文献类型：
--
作者：
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., Jr.
双相抑郁症的现有疗法在起效方面有相当大的滞后。产生快速抗抑郁效果的药理学策略--例如，在几小时或几天内--将对病人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是否在双相抑郁受试者中产生快速抗抑郁作用。一项于2006年10月至2009年6月进行的随机、安慰剂对照、双盲、交叉、添加研究。美国国家心理健康研究所情绪障碍研究中心，位于马里兰州贝塞斯达。18例DSM-IV双相抑郁受试者（难治性）。维持锂或丙戊酸盐治疗水平的受试者在2个试验日（间隔2周）接受盐酸氯胺酮（0.5 mg/kg）或安慰剂静脉输注。在基线和输注后40、80、110和230分钟以及第1、2、3、7、10和14天，使用Montgomery-Asberg抑郁评定量表对受试者进行评定。蒙哥马利-阿斯伯格抑郁评定量表主要疗效指标评分的变化。在40分钟内，与安慰剂相比，接受氯胺酮的受试者的抑郁症状显著改善（d=0.52，95%置信区间[CI]，0.28-0.76）;这种改善在第3天仍然显著。第2天的药物差异效应量最大（d=0.80，95% CI，0.55-1.04）。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例接受氯胺酮的受试者和1例接受安慰剂的受试者出现躁狂症状。氯胺酮一般耐受良好;最常见的不良反应是分离症状，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大而快速的抗抑郁作用。clinicaltrials.gov标识符：NCT 00088699
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. 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. clinicaltrials.gov Identifier: NCT00088699
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影响因子：
2.9
作者：
Altamura, Alfredo Carlo;Dell'Osso, Bernardo;Mundo, Emanuela
通讯作者：
Mundo, Emanuela
影响因子：
3.6
作者：
MELONI, D;GAMBARANA, C;TAGLIAMONTE, A
通讯作者：
TAGLIAMONTE, A
影响因子：
10.6
作者：
Berman, RM;Cappiello, A;Krystal, JH
通讯作者：
Krystal, JH
影响因子：
--
作者：
Merikangas, Kathleen R.;Akiskal, Hagop S.;Kessler, Ronald C.
通讯作者：
Kessler, Ronald C.
影响因子：
3.6
作者：
LAYER, RT;POPIK, P;SKOLNICK, P
通讯作者：
SKOLNICK, P