D-Cycloserine Enhancement of Exposure in Social Phobia

描述(由申请人提供)：社交焦虑症(SAD)是最常见的精神疾病之一，与受影响个人的严重痛苦和功能障碍有关。虽然认知行为疗法(CBT)的治疗结果在SAD的经验性文献中是最好的，但许多患者对这种干预措施没有反应，大多数患者没有缓解。因此，鉴于SAD的患病率和随之而来的发病率，以及它在接受治疗后的持久性，迫切需要开发新的干预措施来改善结果。在CBT中，核心治疗程序包括反复和长期暴露在令人恐惧的社交情况下，当患者在这些刺激下获得安全感时，恐惧就会消失。暴露疗法是基于消除条件性恐惧的动物模型，最近的动物研究绘制了一些与恐惧消退有关的核心途径和神经递质。D-环丝氨酸(DC)是谷氨酸能NDMA受体部位的激动剂，似乎可以增强动物的学习能力，在一些人类试验中，它有助于消除条件性恐惧的过程。因此，从恐惧消退的动物模型和人类的初步研究(包括我们的初步研究)中汇聚的证据表明，DCS可以促进SAD的CBT。我们建议进行一项为期4年的研究，系统地评估CBT增强DCS治疗SAD的疗效。这项研究包括一项随机对照试验，以比较12个CBT疗程的相对短期和长期益处，这些CBT疗程包括5个分布式控制系统增强(50 Mg)疗程，采用相同的CBT方案，其中包括5个安慰剂强化疗程。此外，我们还将探索治疗变化的潜在调解人和调解人。我们将在每个地点对总共192名患者进行随机化，采用相同的方案。我们利用一个由3个治疗地点的研究人员组成的协作团队，帮助确保及时招募足够数量的患者，包括种族多样化的人群。这项研究代表了将长凳研究转化为临床的关键阶段，并测试了一种将药理学和认知行为策略结合起来治疗患者的新方法。这项研究通过评估干预措施来解决一个重要的公共卫生问题，该干预措施可能导致更有效和有效地应用基于经验的心理社会干预措施来治疗SAD。

DESCRIPTION (provided by applicant): Social anxiety disorder (SAD) is among the most common psychiatric conditions and is associated with significant distress and dysfunction in affected individuals. Although treatment with cognitive-behavior therapy (CBT) results in some of the best outcomes in the empirical literature for SAD, many patients do not respond to this intervention and most do not achieve remission. Thus, given the prevalence and attendant morbidity of SAD, and its persistence despite treatment, there is a critical need for the development of novel interventions to improve outcome. In CBT, core therapeutic procedures include repeated and prolonged exposure practices to feared social situations, allowing fears to extinguish as patients acquire a sense of safety in the presence of these stimuli. Exposure therapy is based on animal models of extinction of conditioned fears, and recent animal research has mapped some of the core pathways and neurotransmitters involved in fear extinction. D-cycloserine (DCS), an agonist at the glutamatergic NDMA receptor site appears to augment learning in animals and in some human trials facilitating the process of extinction of conditioned fear. Thus, converging evidence from animal models of fear extinction, and from initial studies in humans, including work from our pilot study, indicates that DCS can facilitate CBT of SAD. We are proposing a 4-year study to systematically assess the efficacy of DCS augmentation of CBT for the treatment of SAD. The study comprises a randomized, controlled trial to compare the relative short-term and long-term benefits of 12 CBT sessions that include 5 DCS-augmented (50 mg) sessions with the same CBT protocol that includes 5 placebo-augmented sessions. In addition, we will explore potential mediators and moderators of treatment change. We will randomize a total of 192 patients with the identical protocol followed at each of the sites. We make use of a collaborating team of investigators across 3 treatment sites to help ensure the timely recruitment of adequate numbers of patients, including an ethnically diverse population. This study represents a crucial stage in translating bench research to the clinic, and testing a novel approach for combining pharmacologic and cognitive-behavioral strategies for treating patients. This study addresses an important public health issue by assessing an intervention that may lead to a more efficient and effective application of empirically based psychosocial interventions for the treatment of SAD.