Mann Karl, Kiefer Falk, Smolka Michael, Gann Horst, Wellek Stefan, Heinz Andreas
Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany.
Alcohol Clin Exp Res. 2009 Apr;33(4):674-83. doi: 10.1111/j.1530-0277.2008.00884.x. Epub 2009 Jan 20.
Alcoholism represents a major public health issue and treating alcohol dependent patients remains an imminent challenge. Evidence based psychotherapies and pharmacotherapies are available. However, when administered to heterogeneous populations of patients effect sizes are only modest. We present the rationale and design of a double-blind randomized trial comparing acamprosate, naltrexone, and placebo. Additionally we subtype patients on the basis of biological and psychometric measures and explore their treatment response to both acamprosate and naltrexone. According to our initial hypothesis, the "relief drinker/craver" is an endophenotype associated with glutamatergic dysfunction who responds to acamprosate. The "reward drinker/craver" is mainly associated with alterations in the dopaminergic and opioidergic system and responds to naltrexone.
The study is planned for 430 patients (2:2:1 for both drugs and placebo) over 12 weeks of medication. All receive manualized counselling to improve compliance (Medical Management) which is extended to 6 months. Subtyping is primarily done using the acoustic startle reflex, functional magnetic resonance imaging, positron emission tomography (in a subset of patients), and the Inventory of Drinking Situations. Relapsers will be re-randomized into a second study where additional psychotherapy (Cognitive Behavioral Intervention) is used in a stepped care approach. Genotyping and additional analyses such as health economy are being done as well. The study follows the assessment methods, treatments, and medications used in the U.S. based COMBINE study, which will allow for a direct comparison between this U.S. study trial and a study performed in Europe.
酒精成瘾是一个重大的公共卫生问题，治疗酒精依赖患者仍然是一项紧迫的挑战。有基于证据的心理治疗和药物治疗方法。然而，当应用于异质性患者群体时，效应大小仅为中等。我们介绍了一项比较阿坎酸、纳曲酮和安慰剂的双盲随机试验的基本原理和设计。此外，我们根据生物学和心理测量指标对患者进行亚型分类，并探索他们对阿坎酸和纳曲酮的治疗反应。根据我们最初的假设，“缓解型饮酒者/渴望者”是一种与谷氨酸能功能障碍相关的内表型，对阿坎酸有反应。“奖赏型饮酒者/渴望者”主要与多巴胺能和阿片样物质系统的改变有关，对纳曲酮有反应。
该研究计划纳入430名患者（药物和安慰剂的比例为2:2:1），进行为期12周的药物治疗。所有患者均接受标准化咨询以提高依从性（医学管理），并延长至6个月。亚型分类主要使用听觉惊吓反射、功能磁共振成像、正电子发射断层扫描（部分患者）和饮酒情境量表。复发者将被重新随机分组进入第二项研究，在该研究中采用逐步护理方法进行额外的心理治疗（认知行为干预）。同时也在进行基因分型和健康经济学等额外分析。该研究遵循美国COMBINE研究中使用的评估方法、治疗方法和药物，这将使这项美国研究试验与在欧洲进行的一项研究能够进行直接比较。
