2/3-Dose Timing of D-cycloserine to Augment CBT for Social Anxiety Disorder

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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.