Efficacy Evaluation of Transdiagnostic CBT for Comorbid Alcohol Use and Anxiety Disorder

项目摘要/摘要 焦虑症(AXD)发生在多达三分之一的酒精依赖患者寻求治疗和 在患有酒精使用障碍(AUD)的人中，与治疗反应差有关。 尽管这种共病对个人和公共健康造成了重大影响，但有效的治疗尚未得到 而且缺乏足够的研究来指导治疗决定。在最近的工作中，我们有 证明了情绪障碍跨诊断治疗的统一方案(UP；Barlow， Fachone等人，2011)显著减少了AUD/AXD共病的大量饮酒，但文拉法辛， 一种被美国FDA批准用于治疗焦虑的药物，尽管减少了，但对饮酒没有影响 焦虑和抑郁。在我们进行的临床试验中，唑尼沙胺(ZON)给药减少了酒精 AUD患者的饮酒量减少，反映在大量饮酒的天数百分比减少； 每天饮酒量，每饮酒天数减少百分比。目前的提案将审查一项 建立对情绪障碍(如焦虑和情绪)的跨诊断认知行为干预 紊乱)，相对于ZON，一种在不工作的情况下直接影响酒精消费的药物 通过降低焦虑的机制。这项建议的中心焦点是检查UP的疗效。 ZON在减少AUD/AXD共病患者饮酒量方面相对较低强度 由采取控制(TC)组成的行为治疗控制，这是一种治疗AUD的新形式，我们 与NIAAA合作开发，与避孕药安慰剂(PLC)结合使用。我们建议服用安慰剂- 对照双盲临床试验分为三组：1)UP组，2)ZON组，3)TC PLC组。经过筛选，所有人都 参与者将接受为期16周的治疗。在第17周和第18周的研究中，Zon将会减少 治疗后评估和后续措施将在治疗后1个月和6个月后进行 治疗后评估。酒精消耗量将使用生态瞬时 评估和时间线遵循回溯程序。抑郁焦虑应激量表、汉密尔顿焦虑 和抑郁评定量表，以及DSM-5的焦虑障碍面谈时间表将用于 测量焦虑和抑郁。与这些评估相辅相成的是审查更高- 与情绪调节障碍相关的秩序、气质变量和核心心理病理机制 已被证明有助于这些疾病的发展和维持，并可能解释 因为临床上可以看到大量的诊断重叠。此外，我们将使用磁共振 波谱(MRS)检测UP和ZON对脑内谷氨酸(Glu)、GSH和 并分析血液样本以测量GSH和其他氧化应激生物标志物。使用MRS 在治疗过程中测量这些神经化学物质的变化可能会带来更好的机制理解 UP和ZON，可能有助于优化这些治疗在AUD患者中的使用。

PROJECT SUMMARY/ABSTRACT Anxiety disorders (AXD) occur in up to one-third of individuals with alcohol dependence seeking treatment and are associated with poor treatment response in people who have comorbid alcohol use disorders (AUD). Despite the major personal and public health impact of this comorbidity, effective treatments have not been established and there is a lack of adequate research to guide treatment decisions. In recent work we have demonstrated that the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders (UP; Barlow, Farchione, et al., 2011) significantly reduced heavy drinking in comorbid AUD/AXD disorders, but venlafaxine, a drug approved by the US FDA for treatment of anxiety, did not have an effect on drinking, despite decreasing anxiety and depression. In clinical trials that we conducted zonisamide (ZON) administration reduced alcohol consumption in individuals with AUD, as reflected by decreased percent days with heavy drinking; decreased drinks consumed per day, and decreased percent days with any drinking. The current proposal will examine an established transdiagnostic cognitive-behavioral intervention for emotional disorders (e.g., anxiety and mood disorders), the UP, relative to ZON, a medication that directly influences alcohol consumption without working through the mechanism of anxiety reduction. The central focus of this proposal is to examine the efficacy of UP and ZON in reducing alcohol consumption in patients with comorbid AUD/AXD, relative to a low intensity behavioral treatment control consisting of Take Control (TC), a novel form of psychotherapy for AUD that we developed in collaboration with the NIAAA, in combination with pill placebo (PLC). We propose a placebo- controlled, double-blind clinical trial with three groups: 1) UP, 2) ZON, and 3) TC+PLC. After screening, all participants will receive treatment for 16 weeks. ZON will be reduced during study weeks 17 and 18, following a post-treatment assessment, and follow-up measures will be obtained one month and six months after the post-treatment assessment. Alcohol consumption will be assessed using both ecological momentary assessment and the time-line follow back procedures. The Depression Anxiety Stress Scale, Hamilton Anxiety and Depression Rating scales, and the Anxiety Disorders Interview Schedule for DSM-5 will be used to measure anxiety and depression. Complementing these assessments are additional scales examining higher- order temperamental variables and core psychopathological mechanisms related to emotional dysregulation that have been shown to contribute to the development and maintenance of these disorders and may account for the high amount of diagnostic overlap seen clinically. Further, we will use magnetic resonance spectroscopy (MRS) to examine the effects of UP and ZON on changes in brain glutamate (Glu), GSH, and GABA levels, and analyze blood samples to measure GSH and other oxidative stress biomarkers. Using MRS to measure changes in these neurochemicals during treatment may lead to a better mechanistic understanding of UP and ZON, and possibly help optimize use of these treatments in patients with AUD.