Efficacy of augmentation of cognitive behavior therapy with weight-adjusted D-cycloserine vs placebo in pediatric obsessive-compulsive disorder: A randomized clinical trial

Eric A. Storch, Sabine Wilhelm, Susan Sprich, Aude Henin, Jamie Micco, Brent J. Small, Joseph McGuire, P. Jane Mutch, Adam B. Lewin, Tanya K. Murphy, Daniel A. Geller

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)779-788
Number of pages10
JournalJAMA psychiatry
Volume73
Issue number8
DOIs
StatePublished - Aug 2016
Externally publishedYes

ASJC Scopus subject areas

  • Psychiatry and Mental health

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