Department of Psychology, University of California Los Angeles, 1285 Franz Hall, Box 951563, Los Angeles, CA 90095-1563, USA.
Psychopharmacology (Berl). 2011 Oct;217(3):341-51. doi: 10.1007/s00213-011-2287-3. Epub 2011 Apr 13.
The available treatments for alcoholism are only modestly effective, and patients vary widely in their treatment response. Quetiapine, an atypical antipsychotic medication with antagonist activity at D1 and D2, 5-HT(1A) and 5-HT(2A), H(1), and α1 and α2 receptors was shown to promote abstinence, reduce drinking days, and reduce heavy drinking days in a 12-week double-blind placebo-controlled trial.
Although quetiapine represents one of the promising pharmacotherapies for the treatment of alcoholism, its mechanisms of action are poorly understood. The objective of this study is to elucidate the biobehavioral mechanisms of action of quetiapine for alcoholism, by examining its effects on subjective intoxication and craving.
A total of 20 non-treatment-seeking alcohol-dependent individuals were randomized to one of the following conditions in a double-blind, placebo-controlled design: (1) quetiapine (400 mg/day); or (2) matched placebo. Participants were on the target medication dose (or matched placebo) for 4 weeks during which they completed weekly assessments of drinking, sleep, mood, and anxiety. Participants completed two counterbalanced intravenous placebo-alcohol administration sessions as well as cue-reactivity assessments.
Analyses revealed a significant effect of quetiapine in reducing craving during the alcohol administration, the alcohol cue-exposure, and the weekly reports of alcohol craving. Quetiapine was also found to reduce subjective intoxication and alcohol-induced sedation during the alcohol administration paradigm.
This study contributes critical new information about mechanisms of response to quetiapine for alcoholism, which, in turn, can inform larger-scale studies and ultimately, clinical practice.
现有的酒精中毒治疗方法效果仅为中等，而且患者对治疗的反应差异很大。喹硫平是一种具有拮抗作用的非典型抗精神病药物，对 D1 和 D2、5-HT（1A）和 5-HT（2A）、H（1）以及α1 和α2 受体均有作用，在一项为期 12 周的双盲安慰剂对照试验中，它被证明可以促进戒酒、减少饮酒天数和减少重度饮酒天数。
虽然喹硫平是治疗酒精中毒的一种有前途的药物疗法之一，但它的作用机制尚不清楚。本研究的目的是通过研究其对主观醉酒和渴望的影响，阐明喹硫平治疗酒精中毒的生物行为学作用机制。
在一项双盲、安慰剂对照设计中，20 名非治疗性寻求酒精依赖的个体被随机分为以下两种条件之一：（1）喹硫平（400mg/天）；或（2）匹配的安慰剂。参与者在目标药物剂量（或匹配的安慰剂）上进行了 4 周的治疗，在此期间他们每周完成饮酒、睡眠、情绪和焦虑的评估。参与者完成了两次平衡的静脉内安慰剂-酒精给药阶段以及线索反应评估。
分析显示，喹硫平对减少酒精给药期间、酒精线索暴露期间和每周酒精渴望报告中的渴望有显著影响。还发现喹硫平可减少酒精给药范式中的主观醉酒和酒精引起的镇静作用。
这项研究为喹硫平治疗酒精中毒的反应机制提供了重要的新信息，这反过来又可以为更大规模的研究提供信息，并最终为临床实践提供信息。
