Topiramate treatment of alcohol dependence in patients with bipolar disorder

描述(由申请人提供)：此K-23奖项申请旨在提高候选人在酒精依赖(AD)与双相情感障碍(BD)共存领域的研究专长。多达60%的双相患者患有终生酒精和药物使用障碍。这些患者的病程更严重，其特点是更多的服务利用率，更多的自杀，更严重的情绪症状，更多的暴力，较差的治疗依从性和功能低下。值得注意的是，到目前为止，只有一项随机对照试验研究了成人AD与BD并存时的治疗方法。托吡酯减少了非精神疾病、酒精依赖人群的饮酒，但托吡酯对BD患者AD的疗效尚不清楚。该项目的目标是在一项随机、安慰剂对照试验中，研究托吡酯辅助治疗双相I或II型障碍患者治疗AD的有效性和安全性。主要的假设是，与安慰剂组相比，随机服用托吡酯的受试者在试验结束时重度饮酒的天数比例较低。 培训计划包括酒精、药物滥用和BD方面的专家的指导和咨询，以及与临床试验设计和分析有关的生物统计学。麦克莱恩医院酒精和药物滥用治疗项目的临床主任罗杰·韦斯博士是导师。卫生研究服务管理局双相情感障碍患者护理和研究卓越中心的联席主任Joseph Calabrese博士和NIMH双相情感试验网络的PI Andrew Nierenberg博士是共同导师。托吡酯治疗AD试验的PI班科尔·约翰逊博士和Divalproex钠治疗AD和BD试验的PI Ihsan Salloum博士是顾问。应用程序的教学部分将特别包括研究设计、高级生物统计学和研究伦理方面的课程。除了为AD与BD的治疗提供重要数据外，该项目奖还将促进候选人向能够在AD和共同发生的情绪障碍方面进行临床试验的独立研究人员过渡。马萨诸塞州波士顿马萨诸塞州总医院双相临床和研究计划

DESCRIPTION (provided by applicant): This K-23 award application is designed to enhance the candidate's research expertise in the area of alcohol dependence (AD) co-occurring with bipolar disorder (BD). As many as 60% of bipolar patients have lifetime alcohol and substance use disorders. These patients have a more severe course of illness, marked by greater service utilization, more suicidality, more severe mood symptoms, increased violence, poor treatment adherence, and lower functioning. Remarkably, only one randomized controlled trial published to date has studied the treatment of AD when it co-occurs with BD in adults. Topiramate decreases drinking in a non-psychiatrically ill, alcohol-dependent population, but the efficacy of topiramate for AD in patients with BD is unknown. The goal of the proposed project is to study the efficacy and safety of adjunctive topiramate treatment of AD in patients with bipolar I or II disorder in a randomized, placebo-controlled trial. The primary hypothesis is that subjects randomized to topiramate will have a lower proportion of heavy drinking days at the completion of the trial compared to the placebo group. The training plan includes mentoring and consultation from experts in alcohol and substance abuse and BD, as well as biostatistics pertaining to clinical trial design and analysis. Dr. Roger Weiss, Clinical Director of the Alcohol and Drug Abuse Treatment Program at McLean Hospital, is the mentor. Dr. Joseph Calabrese, the Co-Director of a Health Research Services Administration's Center of Excellence for the Care and Study of Patients with Bipolar Disorder Comorbid with Drug and Alcohol Abuse, and Dr. Andrew Nierenberg, the PI of the Bipolar Trials Network of the NIMH, are co-mentors. Dr. Bankole Johnson, the PI of trials of topiramate for AD, and Dr. Ihsan Salloum, the PI of a trial of sodium divalproex for AD and BD, are consultants. The didactic component of the application will specifically include coursework in research design, advanced biostatistics, and research ethics. In addition to providing important data for the treatment of AD with BD, this project award will facilitate the candidate's transition to an independent investigator able to conduct clinical trials in AD and co-occuring mood disorders. Bipolar Clinic and Research Program, Massachusetts General Hospital; Boston, MA