A high-throughput clinical assay for testing drug facilitation of exposure therapy.
A high-throughput clinical assay for testing drug facilitation of exposure therapy.
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DOI：
10.1002/da.22047
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发表时间：
2013-07
影响因子：
7.4
通讯作者：
Lenze, Eric J.
中科院分区：
文献类型：
--
作者：
Rodebaugh, Thomas L.;Levinson, Cheri A.;Lenze, Eric J.
关键词：
几项研究表明，D-环丝氨酸（DCS）有助于暴露治疗。我们开发了这种促进作用的标准化测试（即，临床试验），其目的是比完整的临床试验更快且更便宜地测试促进作用。我们开发了一个标准化的简短暴露，其中社交焦虑障碍的参与者进行了录像演讲。在准备演讲之前，参与者被随机分配接受250 mg DCS或匹配安慰剂的单粒胶囊。在演讲过程中，以及大约一周后，在相同情况下的演讲中，对痛苦程度进行了评级。我们对DCS的确保促进效果的主要测量是会话之间的习惯化：与第一次演讲相比，参与者在第二次演讲中是否表现出更少的痛苦。我们还测量了主观焦虑和对审查的恐惧程度。在第一次演讲之前随机接受DCS的受试者比接受安慰剂的受试者更容易表现出会话之间的习惯性。我们还发现DCS组整体表现相关恐惧的减少更大。我们的临床试验能够以高度标准化的方式快速检测暴露促进效应，估计花费的时间和成本仅为临床试验的一小部分。考虑到人们越来越关注使用药物来增强基于学习的心理治疗，这种高通量临床测定方法可能是测试新的作用机制和澄清最佳参数的有利方法，以促进治疗。
Several studies have demonstrated that D-cycloserine (DCS) facilitates exposure therapy. We developed a standardized test of this facilitation (i.e., a clinical assay), with the goal of testing for facilitation more quickly and inexpensively than a full clinical trial. We developed a standardized brief exposure in which participants with social anxiety disorder gave a videotaped speech. Participants were randomized to receive a single capsule of 250mg DCS or a matching placebo prior to preparation for the speech. Distress levels were rated during the speech and again, approximately one week later, during a speech in an identical situation. Our primary measure of DCS’s exposure-facilitating effect was between-session habituation: whether or not the participants showed less distress during the second speech compared to the first. We also measured levels of subjective anxiety and fear of scrutiny. Subjects randomized to receive DCS prior to their first speech were more likely to show between-session habituation than those who received placebo. We also found greater reduction of performance-related fear overall in the DCS group. Our clinical assay was able to detect exposure facilitation effects rapidly and in a highly standardized way, and is estimated to take a fraction of the time and costs of a clinical trial. Given the increasing interest in using medications to enhance learning-based psychotherapy, this high-throughput clinical assay approach may be a favorable method for testing novel mechanisms of action, and clarifying optimal parameters, for therapy facilitation.
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