D-Cycloserine Augmentation of Therapy for Pediatric Obsessive-Compulsive Disorder

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DESCRIPTION (provided by applicant): Exposure and response prevention therapy (E/RP) has proven efficacy for treatment of pediatric obsessive-compulsive disorder (OCD). Yet, E/RP does not help all children and those who benefit often remain symptomatic upon treatment completion. The behavioral theory that underlies E/RP is based on two components, namely fear conditioning and extinction. On a neural level, E/RP incorporates similar mechanisms to those involved in fear conditioning. Antagonists at the N-methyl-D-aspartate (NMDA) glutamatergic receptor, which is involved in learning and memory, block both fear learning and extinction. Evidence suggests that D-Cycloserine (DCS), a partial agonist at the NMDA glutamate receptor, augments associative learning and extinction as a form of learning in animals and humans. Recent clinical trials in adults with other anxiety disorders (acrophobia and social phobia) provided support for DCS dosing as facilitating associative learning that occurs during exposure-based psychotherapy. Given that E/RP is based on the principles of extinction, DCS may augment E/RP in youth with OCD, an anxiety disorder that is conceptually similar to acrophobia and social phobia. With this in mind, I propose to undertake a randomized, double-blind placebo controlled pilot study of DCS to determine whether it had any short-term clinical benefits on E/RP in youth with OCD. Twenty children and adolescents (ages 8-17) with a primary diagnosis of OCD will be randomly assigned to one of two treatment conditions: (1) E/RP plus DCS (25 or 50mg depending on weight), or (2) E/RP plus placebo. All patients will receive 10 sessions of E/RP based on an abbreviated POTS (2004) protocol. Participants will take DCS or placebo 4 hours prior to therapy sessions 4-10 (sessions 1-3 do not involve exposure, thus DCS would have no hypothesized effect). A blinded, independent evaluator will assess participants at three time points. Two of the assessments (Baseline, Post-treatment) will be comprehensive in nature (e.g., diagnostic interview, self-reports, CYBOCS, laboratory tests), whereas the week four assessment will involve administration of the CYBOCS, CGI, CGI-S, and Adverse Symptom Checklist only. Results from this study may have powerful clinical implications by providing preliminary support for pharmacological agents that enhance the effectiveness of standard E/RP. Such agents may have utility in improving outcome, reducing premature therapy termination, and targeting patients who have been treatment refractory.