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

项目总结/摘要 焦虑症（AXD）发生在多达三分之一的酒精依赖寻求治疗的个体中， 与合并酒精使用障碍（AUD）患者的治疗反应不良相关。 尽管这种并发症对个人和公共卫生有重大影响，但有效的治疗方法还没有得到证实。 但是，缺乏足够的研究来指导治疗决定。在最近的工作中， 证明了用于情绪障碍的跨诊断治疗的统一协议（UP; Barlow， Farchione等人，2011）显著减少了合并AUD/AXD障碍的重度饮酒，但文拉法辛， 一种被美国食品和药物管理局批准用于治疗焦虑症的药物，尽管减少了饮酒， 焦虑和抑郁在我们进行的唑尼沙胺（ZON）给药的临床试验中， AUD患者的饮酒量，表现为重度饮酒天数百分比下降; 每天喝的饮料，并减少与任何饮酒的百分比天。目前的建议将审查一项 已建立的用于情绪障碍的跨诊断认知行为干预（例如，焦虑和情绪 疾病），UP，相对于ZON，一种直接影响酒精消费而不起作用的药物 通过减少焦虑的机制。这项建议的中心重点是检查UP的有效性 与低强度相比， 行为治疗控制，包括采取控制（TC），一种新的心理治疗形式的AUD，我们 与NIAAA合作开发，与药丸安慰剂（PLC）组合。我们建议用安慰剂- 对照、双盲临床试验，3组：1）UP、2）ZON和3）TC+PLC。经过筛选，所有 参与者将接受为期16周的治疗。在研究第17周和第18周期间， 治疗后评估和随访措施将在治疗后1个月和6个月获得。 治疗后评估。酒精消费将使用两种生态瞬时 评估和时间线跟踪程序。抑郁焦虑压力量表，汉密尔顿焦虑 和抑郁评定量表，以及DSM-5的焦虑障碍访谈时间表将用于 测量焦虑和抑郁。作为这些评估的补充，还有其他量表，检查较高的- 与情绪失调相关的气质变量和核心精神病理学机制 已经被证明有助于这些疾病的发展和维持， 临床上出现的大量诊断重叠。此外，我们将使用磁共振 通过磁共振波谱（MRS）检查UP和ZON对脑谷氨酸（Glu）、GSH和 GABA水平，并分析血液样本，以测量GSH和其他氧化应激生物标志物。采用MRS 在治疗过程中测量这些神经化学物质的变化可能会导致更好的机制理解 UP和ZON，并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.