Mann Karl, Lehert Philippe, Morgan Marsha Y
Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany.
Alcohol Clin Exp Res. 2004 Jan;28(1):51-63. doi: 10.1097/01.ALC.0000108656.81563.05.
A number of clinical trials have been undertaken to determine the efficacy of acamprosate in the maintenance of abstinence in alcohol-dependent individuals. However, the reported differences in patient populations, treatment duration, and study endpoints make comparisons difficult. An assessment of the efficacy of treatment with acamprosate was, therefore, undertaken using meta-analytical techniques.
All randomized, placebo-controlled trials (RCTs) that fulfilled predetermined criteria were identified using (1) a language unrestricted search of 10 electronic databases; (2) a manual search of relevant journals, symposia, and conference proceedings; (3) cross-referencing of all identified publications; (4) personal communications with investigators; and (5) scrutiny of Merck-Santé's internal reports of all European trials. Study quality was assessed, independently, by three blinded workers. Key outcome data were identified; some outcome variables were recalculated to ensure consistency across trials. The primary outcome measure was continuous abstinence at 6 months; abstinence rates were determined by estimating Relative Benefit (RB).
A total of 19 published 1 unpublished RCTs were identified that fulfilled the selection criteria; 3 were excluded because the documentation available was insufficient to allow adequate assessment. The remaining 17 studies, which included 4087 individuals, 53% of whom received active drug, were of good quality and were otherwise reasonably comparable. There was no evidence of publication bias. Continuous abstinence rates at 6 months were significantly higher in the acamprosate-treated patients (acamprosate, 36.1%; placebo, 23.4%; RB, 1.47; [95% confidence intervals (CI): 1.29-1.69]; p < 0.001). This effect was observed independently of the method used for assigning missing data. The effect sizes in abstinent rates at 3, 6, and 12 months were 1.33, 1.50, and 1.95, respectively. At 12 months, the overall pooled difference in success rates between acamprosate and placebo was 13.3% (95% CI, 7.8-18.7%; number needed to treat, 7.5). Acamprosate also had a modest but significant beneficial effect on retention (6.01%; [95% CI, 2.90-8.82]; p = 0.0106).
Acamprosate has a significant beneficial effect in enhancing abstinence in recently detoxified, alcohol-dependent individuals.
已开展多项临床试验以确定阿坎酸在维持酒精依赖者戒断状态方面的疗效。然而，所报道的患者群体、治疗持续时间和研究终点的差异使得比较变得困难。因此，采用荟萃分析技术对阿坎酸治疗的疗效进行了评估。
通过以下方式确定所有符合预定标准的随机、安慰剂对照试验（RCT）：（1）对10个电子数据库进行不限语言的检索；（2）手动检索相关期刊、研讨会和会议论文集；（3）对所有已识别出版物进行交叉引用；（4）与研究人员进行个人交流；（5）审查默克 - 桑泰公司关于所有欧洲试验的内部报告。由三名盲法工作人员独立评估研究质量。确定关键结局数据；对一些结局变量进行重新计算以确保各试验之间的一致性。主要结局指标是6个月时的持续戒断；通过估计相对获益（RB）来确定戒断率。
共识别出19项已发表和1项未发表的符合入选标准的RCT；排除3项，因为现有文档不足以进行充分评估。其余17项研究包括4087名个体，其中53%接受了活性药物治疗，研究质量良好且在其他方面具有合理可比性。没有证据表明存在发表偏倚。接受阿坎酸治疗的患者6个月时的持续戒断率显著更高（阿坎酸组为36.1%；安慰剂组为23.4%；RB为1.47；[95%置信区间（CI）：1.29 - 1.69]；p < 0.001）。无论采用何种方法处理缺失数据，均观察到这一效果。3个月、6个月和12个月时戒断率的效应大小分别为1.33、1.50和1.95。在12个月时，阿坎酸组和安慰剂组成功率的总体合并差异为13.3%（95%CI，7.8 - 18.7%；需治疗人数为7.5）。阿坎酸对治疗保留率也有适度但显著的有益影响（6.01%；[95%CI，2.90 - 8.82]；p = 0.0106）。
阿坎酸对近期戒断的酒精依赖个体增强戒断具有显著有益作用。
