Dose Timing of D-cycloserine to Augment CBT for Social Anxiety Disorder

描述（由申请人提供）：本申请是为了响应PAR-12-071：精神障碍创新治疗试点研究的协作R34（协作R34）。d -环丝氨酸（DCS）是一种部分n -甲基- d -天冬氨酸谷氨酸激动剂，已被证明可增强对焦虑症的暴露疗法。这种方法是基于最近在理解恐惧消退背后的神经回路方面的研究进展，并基于转化研究的一个显著成功。迄今为止，所有人类临床研究均在接触前至少1小时施用DCS。这种剂量定时策略限制了这种极具前景的增强策略的临床应用，特别是因为越来越多的研究表明DCS增强暴露治疗结果的功效可能取决于暴露疗程的成功。临床前和初步临床数据表明，如果在成功的暴露过程后，在消失试验后立即给予DCS，也可以获得DCS暴露增强效应。拟议的研究建立在现有研究的基础上，通过测试定制的会后DCS管理（即仅在成功的暴露会议之后）对增加暴露治疗的有效性。为了保持本R34研究的高内部效度，我们将招募社交焦虑障碍（SAD）患者参加先前验证的5期CBT方案，并将他们随机分配到：(1)量身定制的期后DCS管理；(2)会前DCS管理；(3)安慰剂给药；(4)非定制的会后DCS管理。主要结果将是社交焦虑严重程度的短期和长期改善：我们预计，在治疗后、1个月和3个月的随访中，定制的会后DCS给药条件将分别优于会前DCS给药、安慰剂给药和非定制的会后DCS给药条件。此外，我们将探索为增加暴露治疗量身定制的会后DCS管理的疗效的潜在调节因子。该应用程序是研究DCS的逻辑下一步。它提供了实现个性化医疗的重要创新举措，为最终开发一种算法提供了第一步，该算法用于在CBT中管理DCS，其目标是最大化治疗焦虑症的功效和成本效益，这是一些最普遍的精神状况，使该项目具有潜在的高公共卫生意义。

DESCRIPTION (provided by applicant): This application is in response to PAR-12-071: Collaborative R34s for Pilot Studies of Innovative Treatments in Mental Disorders (Collaborative R34). D-cycloserine (DCS) is a partial N-methyl-D-aspartate glutamate agonist that has been shown to enhance exposure therapies for anxiety disorders. This approach is grounded in recent research advances in understanding the neural circuitry underlying fear extinction and is based upon one of the striking successes of translational research. All human clinical studies to date have administered DCS at least 1 hour prior to the exposure sessions. This dose-timing strategy limits the clinical utility of this highly promising augmentation strategy, especially sine accumulating research suggest that the efficacy of DCS for enhancing exposure therapy outcomes may depend on the success of exposure sessions. Pre-clinical and initial clinical data suggest that the DCS exposure-augmentation effect can also be obtained when DCS is administered immediately after an extinction trial when it follows successful exposure sessions. The proposed study builds upon this extant research by testing the efficacy of tailored post-session DCS administration (i.e., only following successful exposure sessions) for augmenting exposure therapy. In order to maintain high internal validity in this R34 study, we will enroll patients with social anxiety disorder (SAD) in a previously validated 5-session CBT protocol and randomize them to: (1) tailored post-session DCS administration; (2) pre-session DCS administration; (3) placebo administration; or (4) non-tailored post-session DCS administration. The primary outcomes will be short- and long-term improvements in social anxiety severity: We expect that the tailored post-session DCS administration condition will outperform the pre-session DCS administration, placebo administration, and non-tailored post-session DCS administration conditions, respectively, at posttreatment, 1-month and 3-month follow-up. In addition, we will explore potential moderators of the efficacy of tailored post-session DCS administration for augmenting exposure therapy. This application is the logical next step in the study of DCS. It provides an important innovative move toward the realization of personalized medicine by providing the first step in the eventual development of an algorithm for administering DCS in CBT with the goal of maximizing the efficacy and cost-effectiveness of therapy for anxiety disorders, which are some of the most prevalent mental conditions, making this a project of potentially high public health significance.