Treatment of Alcohol Dependence and Co-Morbid Bipolar Disorder

描述（由申请人提供）：如PA-05-143所示，指导患者导向职业发展奖（K23）的主要目标之一是增加能够将基础生物医学研究的发现转化为临床治疗的临床研究人员。本申请中描述的研究被设计成允许候选人扩展他在共病酒精依赖和双相情感障碍的治疗研究中的训练。酒精依赖在双相情感障碍患者中非常常见，对双相情感障碍的病程有显著的负面影响。很少有治疗研究存在，以指导治疗酒精依赖在这一共病人群。新出现的证据表明，谷氨酸神经传递的改变可能导致酒精依赖和双相情感障碍。拉莫三嗪是一种已知对谷氨酸突触有作用的抗惊厥药物，已被批准用于治疗双相情感障碍，并在对患有双相情感障碍的酒精依赖者的初步研究中显示可减少饮酒。拉莫三嗪也与改善双相情感障碍的神经认知功能有关。拉莫三嗪对酒精依赖和双相情感障碍患者的认知影响尚不清楚。本申请中提出的研究将评估拉莫三嗪对酒精依赖型双相情感障碍患者饮酒、情绪和神经认知结局的疗效。在奖励期间，候选人将接受以下方面的强化培训：（1）酒精中毒和双相情感障碍的神经生物学，2）与酒精依赖和双相情感障碍共病药物治疗评估相关的高级临床试验方法，3）酒精依赖和/或双相情感障碍患者的神经认知评估，以便将这一重要措施纳入未来的治疗试验，4）成功申请以患者为导向的酒精研究独立资助所需的知识和技能，以及5）研究道德和良好的研究实践。拟议的研究是K.23职业发展培训计划的核心，该计划旨在制定一项独立的以患者为导向的研究计划，重点是改善酗酒和严重精神疾病的治疗。 公共卫生相关性：拟议的研究旨在测试药物拉莫三嗪是否有助于减少酒精依赖的双相情感障碍患者的饮酒和改善情绪稳定性。这些研究还将测试药物拉莫三嗪是否可以改善酒精依赖的双相情感障碍患者的认知缺陷。

DESCRIPTION (provided by applicant): As indicated in the PA-05-143, one of the main objectives of the Mentored Patient-Oriented Career Development Award (K23) is to increase the pool of clinical researchers able to translate discoveries from basic biomedical research into clinical treatment. The studies described in the present application are designed to allow the candidate to expand his training in treatment research for comorbid alcohol dependence and bipolar disorder. Alcohol dependence is extremely common in individuals with bipolar disorder and has a significant negative impact on the course of bipolar illness. Few treatment studies exist to guide the treatment of alcohol dependence in this comorbid population. Emerging evidence suggests that alterations of glutamate neurotransmission may contribute to both alcohol dependence and bipolar disorder. Lamotrigine, an anticonvulsant medication with known actions at the glutamate synapse, is approved for the treatment of bipolar disorder and has been shown to reduce drinking in a preliminary study of alcohol- dependent persons with comorbid bipolar disorder. Lamotrigine also has been associated with improved neurocognitive functioning in bipolar disorder. The cognitive effects of lamotrigine in individuals with both alcohol dependence and bipolar disorder are unknown. The studies proposed in this application will evaluate the efficacy of lamotrigine on drinking, mood, and neurocognitive outcomes in alcohol-dependent persons with bipolar disorder. During the award period, the candidate will undergo intensive training in (1) the neurobiology of alcoholism and bipolar disorder, 2) advanced clinical trials methodology as it relates to assessment of pharmacotherapies for comorbid alcohol dependence and bipolar disorder, 3) the assessment of neurocognition in individuals with alcohol dependence and/or bipolar disorder for incorporation of this important measure into future treatment trials, 4) the knowledge and skills necessary to successfully apply for independent funding in patient-oriented alcohol research, and 5) research ethics and good research practice. The proposed studies are central to the K.23 career development training plan to develop an independent patient-oriented research program focused on improving the treatment of alcoholism and severe mental illness. PUBLIC HEALTH RELEVANCE: The proposed studies are designed to test whether the medication lamotrigine may help reduce drinking and improve mood stability in alcohol-dependent persons with bipolar disorder. The studies will also test whether the medication lamotrigine may improve cognitive deficits in alcohol-dependent persons with bipolar disorder.