A high-throughput clinical assay for testing drug facilitation of exposure therapy

一种用于测试药物促进暴露疗法的高通量临床检测方法

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Abstract

OBJECTIVE: 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. METHOD: 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 250 mg DCS or a matching placebo prior to preparation for the speech. Distress levels were rated during the speech and again, approximately 1 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. RESULTS: 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. CONCLUSION: 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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