Efficacy of Augmentation of Cognitive Behavior Therapy With Weight Adjusted d Cycloserine vs Placebo in Pediatric Obsessive Compulsive Disorder: A Randomized Clinical Trial.
IMPORTANCE Cognitive behavior therapy (CBT) among youth with obsessive compulsive disorder (OCD) is effective, but many patients remain symptomatic after intervention. d cycloserine, a partial agonist at the N methyl d aspartate receptor in the amygdala, has been associated with enhanced CBT outcome for OCD among adults but requires evaluation among youth. OBJECTIVES To examine the relative efficacy of weight adjusted d cycloserine (25 or 50 mg) vs placebo augmentation of CBT for youth with OCD and to assess if concomitant antidepressant medication moderated effects. DESIGN, SETTING, AND PARTICIPANTS In a placebo controlled randomized clinical trial, 142 youths (age range, 7 17 years) enrolled between June 1, 2011, and January 30, 2015, at 2 academic health science centers (University of South Florida and Massachusetts General Hospital) with a primary diagnosis of OCD were randomized in a double blind fashion to d cycloserine plus CBT or placebo plus CBT. Intent to treat analysis was performed. INTERVENTIONS Patients were randomly assigned in a 1:1 ratio to either 10 sessions of d cycloserine plus CBT or placebo plus CBT. d cycloserine (25 or 50 mg) or placebo was taken 1 hour before sessions 4 through 10. MAIN OUTCOMES AND MEASURES Children's Yale Brown Obsessive Compulsive Scale at randomization, biweekly, midtreatment, and posttreatment. Secondary outcomes included the Clinical Global Impressions Severity or Clinical Global Impressions Improvement, remission status, Children's Depression Rating Scale, Multidimensional Anxiety Scale for Children, and Children's Obsessive Compulsive Impact Scale Parent Version. RESULTS The study cohort comprised 142 participants. Their mean (SD) age was 12.7 (2.9) years, and 53.5% (76 of 142) were female. A mixed effects model using all available data indicated significant declines in the Children's Yale Brown Obsessive Compulsive Scale total score and Clinical Global Impressions Severity. No significant interaction between treatment group and changes in the Children's Yale Brown Obsessive Compulsive Scale and Clinical Global Impressions Severity indicated that the d cycloserine plus CBT group and the placebo plus CBT group declined at similar rates per assessment point on the Children's Yale Brown Obsessive Compulsive Scale total score (estimate, 2.31, 95% CI, 2.79 to 1.83 and estimate, 2.03, 95% CI, 2.47 to 1.58, respectively) and Clinical Global Impressions Severity (estimate, 0.29, 95% CI, 0.35 to 0.22 and estimate, 0.23, 95% CI, 0.29 to 0.17, respectively) No group differences in secondary outcomes were present. Antidepressant medication use at baseline did not moderate changes for either group. CONCLUSIONS AND RELEVANCE d cycloserine augmentation of CBT did not confer additional benefit relative to placebo among youth with OCD. Other augmentation approaches should be examined to enhance outcome. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00864123.
JAMA psychiatry