Effect of Acamprosate on Magnetic Resonance Spectroscopy Measures of Central Glutamate in Detoxified Alcohol-Dependent Individuals A Randomized Controlled Experimental Medicine Study
Effect of Acamprosate on Magnetic Resonance Spectroscopy Measures of Central Glutamate in Detoxified Alcohol-Dependent Individuals A Randomized Controlled Experimental Medicine Study
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DOI：
10.1001/archgenpsychiatry.2010.125
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发表时间：
2010-10-01
影响因子：
--
通讯作者：
Heilig, Markus
中科院分区：
文献类型：
--
作者：
Umhau, John C.;Momenan, Reza;Heilig, Markus
背景：阿坎酸被批准用于治疗酒精中毒，但其作用机制仍不清楚。动物研究结果表明，持续的高谷氨酸能状态有助于酒精中毒的发病机制，而阿坎酸可能通过干预这一过程来发挥其作用。这些研究结果缺乏人工翻译。目的：通过质子核磁共振波谱 (H-1-MRS) 测量，检查阿坎酸是否调节最近戒酒的酒精依赖患者的中央谷氨酸水平指数。设计：一项为期 4 周的双盲、安慰剂对照、随机对照实验医学研究，在第 4 天和第 25 天获得 H-1-MRS 测量值。地点：NIH 临床的住院研究单位中心.患者：33 名符合 DSM-IV 酒精依赖标准的患者，入院时在医学监督下戒断持续饮酒。干预：入院时开始服用阿坎酸（初始口服负荷，随后每日 1998 毫克）或匹配安慰剂 4 周。主要结果指标：使用前部单体素 H-1-MRS 确定的谷氨酸与肌酸比率扣带回。还收集了探索性神经内分泌、生化和行为结果，以及安全性和耐受性相关措施。 结果：阿坎酸随时间推移对谷氨酸与肌酸的比率有高度显着的抑制作用（时间 X 治疗相互作用：F-1、F-29 = 13.5，P
Context: Acamprosate is approved for the treatment of alcoholism, but its mechanism of action remains unclear. Results of animal studies suggest that a persistent hyperglutamatergic state contributes to the pathogenesis of alcoholism and that acamprosate may exert its actions by intervening in this process. Human translation of these findings is lacking.Objective: To examine whether acamprosate modulates indices of central glutamate levels in recently abstinent alcohol-dependent patients as measured using proton nuclear magnetic resonance spectroscopy (H-1-MRS).Design: A 4-week, double-blind, placebo-controlled, randomized controlled experimental medicine study, with H-1-MRS measures obtained on days 4 and 25.Setting: An inpatient research unit at the NIH Clinical Center.Patients: Thirty-three patients who met the DSM-IV criteria for alcohol dependence and who were admitted for medically supervised withdrawal from ongoing alcohol use.Intervention: Four weeks of acamprosate (initial oral loading followed by 1998 mg daily) or 'matched placebo, initiated at the time of admission.Main Outcome Measures: The glutamate to creatine ratio as determined using single-voxel H-1-MRS in the anterior cingulate. Exploratory neuroendocrine, biochemical, and behavioral outcomes were also collected, as were safety- and tolerability-related measures.Results: There was a highly significant suppression of the glutamate to creatine ratio across time by acamprosate (time X treatment interaction: F-1,F-29= 13.5, P