Oral topiramate for treatment of alcohol dependence: a randomised controlled trial
Oral topiramate for treatment of alcohol dependence: a randomised controlled trial
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DOI：
10.1016/s0140-6736(03)13370-3
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发表时间：
2003-05-17
期刊：
影响因子：
168.9
通讯作者：
Ma, JZ
中科院分区：
文献类型：
--
作者：
Johnson, BA;Ait-Daoud, N;Ma, JZ
背景托吡酯是一种氨基磺酸果糖衍生物，可能通过同时促进γ-氨基丁酸活性和抑制谷氨酸功能来抑制中皮质边缘多巴胺的释放，从而拮抗酒精与滥用倾向相关的奖赏效应。我们的目的是观察托吡酯在治疗酒精依赖方面是否比安慰剂更有效。方法我们进行了一项为期12周的双盲随机对照临床试验，比较口服托吡酯和安慰剂对150名酒精依赖患者的治疗效果。在这150人中，75人被分配接受托吡酯(每天递增剂量25-300毫克)，75人接受安慰剂作为每周标准化用药依从性管理的辅助。主要疗效变量是：自我报告饮酒(每天饮酒，每天饮酒，重度饮酒天数百分比，戒酒天数百分比)和血浆γ-谷氨酰转移酶，这是饮酒的客观指标。研究结束时发现，与安慰剂组相比，服用托吡酯的参与者每天饮酒量减少2.88%(95%氯-4.50%至-1.27%)(p=0.0006)，每天饮酒量减少3.10%(-4.88%至-1.31)(p=0.0009)，重度饮酒天数减少27.6%(p=0.0003)，戒酒天数增加26.2%(p=0.0003)，对数血浆γ-谷氨酰转移酶比值为0.07%(-0.11%~-0.02%)(p=0.0046)。托吡酯引起的渴求差异也明显大于安慰剂，与自我报告的饮酒变化幅度相似，并与它们高度相关。在酒精依赖治疗中，解释托吡酯(每天最多300毫克)比安慰剂更有效，作为标准化药物依从性管理的辅助。
Background Topiramate, a sulphamate fructopyranose derivative, might antagonise alcohol's rewarding effects associated with abuse liability by inhibiting mesocorticolimbic dopamine release via the contemporaneous facilitation of gamma-amino-butyric acid activity and inhibition of glutamate function. We aimed to see whether topiramate was more effective than placebo as a treatment for alcohol dependence.Methods We did a double-blind randomised controlled 12-week clinical trial comparing oral topiramate and placebo for treatment of 150 individuals with alcohol dependence. Of these 150 individuals, 75 were assigned to receive topiramate (escalating dose of 25-300 mg per day) and 75 had placebo as an adjunct to weekly standardised medication compliance management. Primary efficacy variables were: self-reported drinking (drinks per day, drinks per drinking day, percentage of heavy drinking days, percentage of days abstinent) and plasma gamma-glutamyl transferase, an objective index of alcohol consumption. The secondary efficacy variable was self-reported craving.Findings At study end, participants on topiramate, compared with those on placebo, had 2.88 (95% Cl -4.50 to -1.27) fewer drinks per day (p=0.0006), 3.10 (-4.88 to -1.31) fewer drinks per drinking day (p=0.0009), 27.6% fewer heavy drinking days (p=0.0003), 26.2% more days abstinent (p=0.0003), and a log plasma gamma-glutamyl transferase ratio of 0.07 (-0.11 to -0.02) less (p=0.0046). Topiramate-induced differences in craving were also significantly greater than those of placebo, of similar magnitude to the self-reported drinking changes, and highly correlated with them.Interpretation Topiramate (up to 300 mg per day) is more efficacious than placebo as an adjunct to standardised medication compliance management in treatment of alcohol dependence.