The Use of D-Cycloserine to Augment Intensive Cognitive Behavioral Therapy for Pediatric Obsessive Compulsive Disorder

Although research has demonstrated clear benefits of cognitive behavioral treatment for children with obsessive-compulsive disorder, typical rates of treatment response are far from absolute and even treatment responders tend to exhibit continuing symptoms. In one of the most cited and largest child OCD treatment study to date, only 39% of the participants showed a robust response to a 12-week course of CBT. In recent years, the basic research finding that D-Cyclocerine, a partial N-methyl-Daspartate (NMDA) receptor agonist, enhances extinction of learned fear among rats2 has generated significant interest among clinical researchers. This is not surprising given that the core component of CBT involves exposing the individual to the feared stimuli in the absence of the feared consequence (ie, extinction training). Indeed, data from several trials (for adults with social anxiety, specific phobia, and OCD) indicate that compared to placebo, when DCS is added to exposure, participants tend to respond faster and at higher rates to treatment. This significant development in clinical treatment for anxiety disorders has been examined in only one pilot study among children with OCD. In this study, the effects of DCS were modest but the methodology utilized (eg., no objective symptom measure, lack of information regarding aspects of treatment) make the results difficult to interpret. The present study will help clarify, albeit in only a preliminary way, whether DCS is a promising addition to the treatment options available to the OCD treatment provider. The greatest utility of the augmentation strategy may be the capability to hasten the rate of improvement, and thus, decrease the discomfort of treatment and decrease treatment drop-out.

*Research Design and Methods: Describe in detail the design and methodology of the study.

A) Overview We propose to examine the preliminary efficacy of D-cycloserine augmentation of eight sessions (two weeks) of intensive exposure and response prevention treatment administered to youngsters aged 7-17 with primary OCD. All subjects will be receiving clinical treatment through the UCLA Child OCD Intensive Outpatient Program and DCS will be introduced, and will be delivered during the third and fourth week (starting on the 9th IOP treatment visit) of the subject's participation in the IOP clinical treatment.

To best address these aims, a total twenty-six 7-17 year-old children and adolescents will be recruited from UCLA Child OCD Intensive Outpatient Program. After completing an eligibility screen, all qualified participants will undergo a baseline evaluation including diagnostic as well as symptom assessments before randomization or treatment. This baseline assessment will be completed no more than 5 days prior to their 9th treatment visit (i.e., their first day of DCS medication).

Following these assessments, subjects will be randomized to receive either DCS or placebo (PBO) 4 times weekly immediately preceding their treatment session for two weeks of treatment (4 sessions weekly). Study participants will receive the same cognitive-behavior treatment through IOP whether they are in the active (DCS) or placebo (PBO) condition. In addition, all subjects will continue clinical treatment in IOP for as long as clinically indicated. However, responders at study week 2 (CGI-I = 1 or 2) will be reassessed at three-month follow-up to establish durability of early response. Parents will participate in the child's clinical assessment, and fill out self-reports, to better help the research team understand the child's functioning. Please see attached table of procedures for overview.