Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, P.O. Box 800623, Charlottesville, VA 22908-0623, USA.
Curr Pharm Des. 2010;16(19):2103-12. doi: 10.2174/138161210791516404.
Predicated upon a neuropharmacological conceptual model, there is now solid clinical evidence to support the efficacy of topiramate for the treatment of alcohol dependence. Topiramate treatment can be initiated whilst the alcohol-dependent individual is still drinking - just when crisis intervention is most likely to be needed by a patient with or without his or her family asking the health practitioner for assistance. Because topiramate can be paired with a brief intervention, there is now the exciting possibility of treating most alcohol- dependent individuals in office-based practice or generic treatment settings. Topiramate's additional effects on other impulsedyscontrol disorders make it a particularly interesting compound for the treatment of other comorbid drug or psychiatric disorders. Additionally, future studies should explore whether topiramate can be combined with other putative therapeutic agents to increase its efficacy. One notable clinical challenge in the development of topiramate as a pharmacotherapy to treat alcohol dependence is the determination of the smallest dose that can result in efficacy, thereby achieving the optimum balance between therapeutic benefit and adverse event profile. Animal data do provide support for topiramate's general anti-drinking effects but also indicate that its mechanisms of action might rely on several complex pharmacobehavioral changes. Additional preclinical studies are needed to elucidate more clearly the basic mechanistic processes that underlie topiramate's efficacy as a treatment for alcohol dependence. Preclinical information that topiramate may have differential effects based on genetic vulnerability opens up the possibility of future methods to optimize treatment.
基于神经药理学的概念模型,现在有确凿的临床证据支持托吡酯治疗酒精依赖的疗效。托吡酯治疗可以在酒精依赖者仍在饮酒时开始——这正是患者最有可能需要危机干预的时候,无论他或她的家人是否要求医疗保健提供者提供帮助。由于托吡酯可以与简短的干预措施结合使用,因此现在有可能在基于办公室的实践或普通治疗环境中治疗大多数酒精依赖者。托吡酯对其他冲动控制障碍的额外作用使其成为治疗其他共病药物或精神障碍的特别有趣的化合物。此外,未来的研究应该探索托吡酯是否可以与其他假定的治疗剂联合使用,以提高其疗效。托吡酯作为治疗酒精依赖的药物治疗开发中的一个显著临床挑战是确定可以产生疗效的最小剂量,从而在治疗益处和不良事件谱之间达到最佳平衡。动物数据确实支持托吡酯的一般戒酒作用,但也表明其作用机制可能依赖于几种复杂的药物行为变化。需要进一步的临床前研究来更清楚地阐明托吡酯作为治疗酒精依赖的有效性的基本机制过程。托吡酯可能基于遗传易感性产生差异效应的临床前信息为未来优化治疗的方法开辟了可能性。