Miranda Robert, MacKillop James, Treloar Hayley, Blanchard Alexander, Tidey Jennifer W, Swift Robert M, Chun Thomas, Rohsenow Damaris J, Monti Peter M
Center for Alcohol and Addiction Studies, Brown University, Providence, RI, USA.
Addict Biol. 2016 Jan;21(1):171-82. doi: 10.1111/adb.12192. Epub 2014 Oct 29.
Topiramate reduces drinking, but little is known about the mechanisms that precipitate this effect. This double-blind randomized placebo-controlled study assessed the putative mechanisms by which topiramate reduces alcohol use among 96 adult non-treatment-seeking heavy drinkers in a laboratory-based alcohol cue reactivity assessment and in the natural environment using ecological momentary assessment methods. Topiramate reduced the quantity of alcohol heavy drinkers consumed on drinking days and reduced craving while participants were drinking but did not affect craving outside of drinking episodes in either the laboratory or in the natural environment. Topiramate did not alter the stimulant or sedative effects of alcohol ingestion during the ascending limb of the blood alcohol curve. A direct test of putative mechanisms of action using multilevel structural equation mediation models showed that topiramate reduced drinking indirectly by blunting alcohol-induced craving. These findings provide the first real-time prospective evidence that topiramate reduces drinking by reducing alcohol's priming effects on craving and highlight the importance of craving as an important treatment target of pharmacotherapy for alcoholism.
托吡酯可减少饮酒量，但对于引发这一效果的机制却知之甚少。这项双盲随机安慰剂对照研究，在基于实验室的酒精线索反应性评估以及使用生态瞬时评估方法的自然环境中，评估了托吡酯减少96名未寻求治疗的成年重度饮酒者酒精使用量的假定机制。托吡酯减少了重度饮酒者在饮酒日的饮酒量，并在参与者饮酒时减少了渴望感，但在实验室或自然环境中，对饮酒时段之外的渴望感并无影响。在血酒精曲线上升阶段，托吡酯并未改变酒精摄入的兴奋或镇静作用。使用多水平结构方程中介模型对假定作用机制进行的直接测试表明，托吡酯通过减弱酒精诱发的渴望感间接减少了饮酒量。这些发现提供了首个实时前瞻性证据，即托吡酯通过减少酒精对渴望感的启动效应来减少饮酒量，并突出了渴望感作为酒精中毒药物治疗重要靶点的重要性。
