title: Efficacy of Augmentation of Cognitive Behavior Therapy With Weight-Adjusted d-Cycloserine vs Placebo in Pediatric Obsessive-Compulsive Disorder: A Randomized Clinical Trial.
abstract: OBJECTIVE
  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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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
  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.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00864123.
authors.affiliation: Department of Pediatrics, University of South Florida, Tampa2Department of Health Policy and Management, University of South Florida, Tampa3Department of Psychiatry and Behavioral Neurosciences, University of South Florida, Tampa4Rogers Behavioral Health-
authors.forename: Eric A
authors.initials: EA
authors.lastname: Storch
authors.affiliation: Department of Psychiatry, Massachusetts General Hospital, Boston7Department of Psychiatry, Harvard Medical School, Boston, Massachusetts.
authors.forename: Sabine
authors.initials: S
authors.lastname: Wilhelm
authors.affiliation: Department of Psychiatry, Massachusetts General Hospital, Boston7Department of Psychiatry, Harvard Medical School, Boston, Massachusetts.
authors.forename: Susan
authors.initials: S
authors.lastname: Sprich
authors.affiliation: Department of Psychiatry, Massachusetts General Hospital, Boston7Department of Psychiatry, Harvard Medical School, Boston, Massachusetts.
authors.forename: Aude
authors.initials: A
authors.lastname: Henin
authors.affiliation: Department of Psychiatry, Massachusetts General Hospital, Boston7Department of Psychiatry, Harvard Medical School, Boston, Massachusetts.
authors.forename: Jamie
authors.initials: J
authors.lastname: Micco
authors.affiliation: School of Aging Studies, University of South Florida, Tampa.
authors.forename: Brent J
authors.initials: BJ
authors.lastname: Small
authors.affiliation: Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles.
authors.forename: Joseph
authors.initials: J
authors.lastname: McGuire
authors.affiliation: Department of Pediatrics, University of South Florida, Tampa.
authors.forename: P Jane
authors.initials: PJ
authors.lastname: Mutch
authors.affiliation: Department of Pediatrics, University of South Florida, Tampa3Department of Psychiatry and Behavioral Neurosciences, University of South Florida, Tampa.
authors.forename: Adam B
authors.initials: AB
authors.lastname: Lewin
authors.affiliation: Department of Pediatrics, University of South Florida, Tampa3Department of Psychiatry and Behavioral Neurosciences, University of South Florida, Tampa5Johns Hopkins All Children's Hospital, St Petersburg, Florida.
authors.forename: Tanya K
authors.initials: TK
authors.lastname: Murphy
authors.affiliation: Department of Psychiatry, Massachusetts General Hospital, Boston7Department of Psychiatry, Harvard Medical School, Boston, Massachusetts.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Geller
mesh_terms: D000293:Adolescent; D000679:Amygdala / Q000187:drug effects; D001835:Body Weight; D002648:Child; D015928:Cognitive Behavioral Therapy; D003131:Combined Modality Therapy; D003523:Cycloserine / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D009771:Obsessive-Compulsive Disorder / Q000175:diagnosis / Q000523:psychology / Q000628:therapy*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D003523:Cycloserine