Olmsted Christina L, Kockler Denise R
Virginia Commonwealth University Health System/Medical College of Virginia Hospitals, Richmond, VA 23298, USA.
Ann Pharmacother. 2008 Oct;42(10):1475-80. doi: 10.1345/aph.1L157. Epub 2008 Aug 12.
To evaluate the evidence for the use of topiramate for alcohol dependence.
MEDLINE (1966-June 2008) and Cochrane Database (2008, Issue 1) searches were conducted using the search terms alcohol dependence and topiramate. Bibliographies of selected articles were examined for additional data sources.
English-language, randomized, controlled trials evaluating topiramate for treatment of alcohol dependence in humans were selected for review. Three randomized controlled trials and 2 reanalyses were identified. Findings pertaining to efficacy and safety were extracted.
Evidence suggests that topiramate antagonizes excitatory glutamate receptors, inhibits dopamine release, and enhances inhibitory gamma-aminobutyric acid function. These mechanisms may be significant in the treatment of alcohol dependence. Controlled trials have described the use of topiramate, titrated up to 300 mg daily, for alcohol dependence, and have reported decreases in drinking behavior and improvements in quality of life. Adverse effects associated with topiramate included abnormal skin sensation, dizziness, taste perversion, anorexia, pruritus, and difficulty with memory and concentration. In one of the reviewed trials, adverse effects did not account for an increased withdrawal rate. However, in another, when topiramate was titrated over a shortened time period, an increased withdrawal rate was seen. Recently, topiramate has been reported to increase suicide risk, primarily in patients with epilepsy. No cases of suicide were recorded in the alcohol dependence trials.
Results of published trials are promising, showing efficacy for drinking outcomes and quality of life as well as general safety. However, additional larger, longer-term trials are needed to establish the optimal patient type that would benefit most from topiramate treatment in addition to dosing, duration of treatment, and tolerability of topiramate for alcohol dependence. At this time, data are insufficient to support using topiramate in conjunction with brief weekly compliance counseling as a first-line agent for alcohol dependence.
评估托吡酯用于酒精依赖治疗的证据。
使用检索词“酒精依赖”和“托吡酯”对MEDLINE（1966年 - 2008年6月）及Cochrane数据库（2008年第1期）进行检索。查阅所选文章的参考文献以获取其他数据来源。
选取评估托吡酯治疗人类酒精依赖的英文随机对照试验进行综述。共识别出三项随机对照试验和两项再分析。提取有关疗效和安全性的研究结果。
有证据表明，托吡酯可拮抗兴奋性谷氨酸受体、抑制多巴胺释放并增强抑制性γ - 氨基丁酸功能。这些机制在酒精依赖治疗中可能具有重要意义。对照试验描述了使用托吡酯治疗酒精依赖，每日滴定至300毫克，报告饮酒行为减少且生活质量改善。与托吡酯相关的不良反应包括皮肤感觉异常、头晕、味觉异常、厌食、瘙痒以及记忆和注意力方面的困难。在一项综述试验中，不良反应并未导致戒断率增加。然而，在另一项试验中，当托吡酯在较短时间内滴定给药时，观察到戒断率增加。最近，有报道称托吡酯会增加自杀风险，主要是在癫痫患者中。酒精依赖试验中未记录到自杀病例。
已发表试验的结果很有前景，显示出对饮酒结局和生活质量有效且总体安全。然而，需要更多更大规模、更长期的试验来确定最能从托吡酯治疗中获益的最佳患者类型，以及托吡酯治疗酒精依赖的给药剂量、治疗持续时间和耐受性。目前，数据不足以支持将托吡酯与每周一次的简短依从性咨询联合使用作为酒精依赖的一线治疗药物。
