阿坎酸治疗酒依赖的12周多中心随机双盲对照研究

A 12-week randomized,double-blind,placebo-controlled multicenter clinical trial of acamprosate for the treatment of alcohol dependence

目的:评价阿坎酸治疗酒依赖的疗效和安全性。方法:本研究采用随机、双盲、安慰剂对照的多中心临床试验设计。研究对象是符合美国精神障碍诊断与统计手册第4版(DSM-IV)酒依赖诊断标准的门诊或者住院患者。共入组230例,一组(n=116)用阿坎酸(体质量<60 kg,1332 mg/d;≥60kg,1998 mg/d)治疗,另一组(n=114)接受安慰剂治疗,连续治疗12周。以累计戒酒天数(CAD)与校正累积戒酒持续时间(CCAD)、每次访视的复饮率、首次复饮时间作为评价疗效的主要指标。以饮酒次数、饮酒量、可视渴求量表评分、血γ-谷氨酰转移酶水平为评价疗效的次要指标。根据生命体征、实验室及心电图检查、不良事件报告评价安全性。结果:阿坎酸组与安慰剂组在累计戒酒天数[(43.7±34.7)d vs.(38.9±35.8)d]、校正累积戒酒持续时间[(52.0±41.3)%vs.(46.3±42.6)%]、每次访视的复饮率以及首次复饮时间分布等主要疗效评价指标均无统计学差异(均P>0.05)。但在治疗12周后,阿坎酸组患者饮酒量的等级为戒除和小于5标准杯/d的比例(88.1%vs.78.7%)高于安慰剂组,可视渴求量表分[(2.6±2.3)vs.(3.3±2.9)]低于安慰剂组(均P<0.05)。阿坎酸组和安慰剂组的不良事件发生率差异无统计学意义(22.6%vs.19.3%,P>0.05)。阿坎酸组最常见的不良反应是腹泻和皮疹,与安慰剂组相比腹泻发生率(4.9%vs.3.2%)和皮疹发生率(3.9%vs.2.1%)无统计学差异(均P>0.05)。结论:阿坎酸对减少酒依赖患者饮酒量、降低渴求等方面的疗效优于安慰剂,并且安全性良好。

Objective： To evaluate the efficacy and safety of acamprosate in treating patients with alcohol dependence. Methods： A randomized, double-blind, placebo-controlled multicenter clinical trial was conducted. The di- agnosis of alcohol dependence was made according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition （DSM-IV） criteria. All 230 patients received 12 weeks treatment with either acamprosate （weight 〈 60 kg, 1332 mg/d; weight ≥ 60 kg, 1998 mg/d. n = 116） or placebo （n = 114）. The primary efficacy measures were the cumulative abstinence duration （CAD） and corrected cumulative abstinence duration （CCAD）, relapse rate of every visit, time to first drink. The secondary efficacy measures were the drinking times, the number of drinks per drinking day, visual analog scale （ VAS）＇ for alcohol craving, y-glutamyl transferase. The safety measures were the vital signs, laboratory tests, electrocardiography and adverse event report. Results： There were no significant differ- ences of all the primary efficacy measures [CAD, （43.7 ±34. 7） d vs. （38.9 ±35. 8） d; CCAD, （52. 0 ±41.3） % vs. （46. 3 ±42. 6） % ] and adverse event report rates （22. 6% vs. 19. 3% ） between acamprosate group and placebo group. But the rate of withdraw and less than 5 standard drinks per day （88.1% vs. 78. 7%） was higher and the points of visual analog scale for alcohol craving [（2. 6 ±2. 3） vs. （3.3 ±2. 9）] was lower in acamprosate group at the last visit （Ps 〈 0. 05）. The most common treatment-related adverse events in acamprosate group were diarrhea and erythra. Conclusion： The results show that acamprosate appears to be more efficacious for decreasing the num- ber of drinks per drinking day and alcohol craving than placebo. It has similar safety to placebo in treatment of alco- hol dependence.