TY - JOUR
T1 - Efficacy of augmentation of cognitive behavior therapy with weight-adjusted D-cycloserine vs placebo in pediatric obsessive-compulsive disorder
T2 - A randomized clinical trial
AU - Storch, Eric A.
AU - Wilhelm, Sabine
AU - Sprich, Susan
AU - Henin, Aude
AU - Micco, Jamie
AU - Small, Brent J.
AU - McGuire, Joseph
AU - Mutch, P. Jane
AU - Lewin, Adam B.
AU - Murphy, Tanya K.
AU - Geller, Daniel A.
N1 - Publisher Copyright:
Copyright 2016 American Medical Association. All rights reserved.
PY - 2016/8
Y1 - 2016/8
N2 - 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.
AB - 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.
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U2 - 10.1001/jamapsychiatry.2016.1128
DO - 10.1001/jamapsychiatry.2016.1128
M3 - Article
C2 - 27367832
AN - SCOPUS:84982802782
SN - 2168-622X
VL - 73
SP - 779
EP - 788
JO - JAMA psychiatry
JF - JAMA psychiatry
IS - 8
ER -