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Efficacy of Augmentation of Cognitive Behavior Therapy With Weight-Adjusted d-Cycloserine vs Placebo in Pediatric Obsessive-Compulsive Disorder: A Randomized Clinical Trial.

ABSTRACT: 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.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.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.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.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.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.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.clinicaltrials.gov Identifier: NCT00864123.

SUBMITTER: Storch EA

PROVIDER: S-EPMC5734635 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Efficacy of Augmentation of Cognitive Behavior Therapy With Weight-Adjusted d-Cycloserine vs Placebo in Pediatric Obsessive-Compulsive Disorder: A Randomized Clinical Trial.

Storch Eric A EA Wilhelm Sabine S Sprich Susan S Henin Aude A Micco Jamie J Small Brent J BJ McGuire Joseph J Mutch P Jane PJ Lewin Adam B AB Murphy Tanya K TK Geller Daniel A DA

JAMA psychiatry 20160801 8

<h4>Importance</h4>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.<h4>Objectives</h4>To examine the relative efficacy of weight-adjusted d-cycloserine (25 or 50 mg) vs placebo augmentation of CBT for ...[more]

PMID: 27367832

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Project description:ContextThe extant literature on the treatment of pediatric obsessive-compulsive disorder (OCD) indicates that partial response to serotonin reuptake inhibitors (SRIs) is the norm and that augmentation with short-term OCD-specific cognitive behavior therapy (CBT) may provide additional benefit.ObjectiveTo examine the effects of augmenting SRIs with CBT or a brief form of CBT, instructions in CBT delivered in the context of medication management.Design, setting, and participantsA 12-week randomized controlled trial conducted at 3 academic medical centers between 2004 and 2009, involving 124 pediatric outpatients between the ages of 7 and 17 years with OCD as a primary diagnosis and a Children's Yale-Brown Obsessive Compulsive Scale score of 16 or higher despite an adequate SRI trial.InterventionsParticipants were randomly assigned to 1 of 3 treatment strategies that included 7 sessions over 12 weeks: 42 in the medication management only, 42 in the medication management plus instructions in CBT, and 42 in the medication management plus CBT; the last included 14 concurrent CBT sessions.Main outcome measuresWhether patients responded positively to treatment by improving their baseline obsessive-compulsive scale score by 30% or more and demonstrating a change in their continuous scores over 12 weeks.ResultsThe medication management plus CBT strategy was superior to the other 2 strategies on all outcome measures. In the primary intention-to-treat analysis, 68.6% (95% CI, 53.9%-83.3%) in the plus CBT group were considered responders, which was significantly better than the 34.0% (95% CI, 18.0%-50.0%) in the plus instructions in CBT group, and 30.0% (95% CI, 14.9%-45.1%) in the medication management only group. The results were similar in pairwise comparisons with the plus CBT strategy being superior to the other 2 strategies (P < .01 for both). The plus instructions in CBT strategy was not statistically superior to medication management only (P = .72). The number needed-to-treat analysis with the plus CBT vs medication management only in order to see 1 additional patient at week 12, on average, was estimated as 3; for the plus CBT vs the plus instructions in CBT strategy, the number needed to treat was also estimated as 3; for the plus instructions in CBT vs medication management only the number needed to treat was estimated as 25.ConclusionsAmong patients aged 7 to 17 years with OCD and partial response to SRI use, the addition of CBT to medication management compared with medication management alone resulted in a significantly greater response rate, whereas augmentation of medication management with the addition of instructions in CBT did not.Trial registrationclinicaltrials.gov Identifier: NCT00074815.

Project description:UnlabelledAbstract Objective: Research on D-cycloserine (DCS), a partial N-methyl-d-aspartic acid (NMDA) agonist, has suggested that it may enhance exposure-based therapies for anxiety disorders. RESULTS with DCS in adult posttraumatic stress disorder (PTSD) have been conflicting; however, no data have been reported on children with PTSD. Although many individuals with PTSD respond to exposure-based cognitive behavioral therapy (CBT), there are subgroups of individuals who are nonresponders, and many responders still have substantial residual symptoms. This randomized, triple-blind, placebo-controlled study tested DCS as an adjunct to CBT to improve and speed treatment response for PTSD in youth.MethodsSeven to 18 year-old youth with exposure to trauma and PTSD were offered a 12 session, manualized CBT treatment. Those who remained in treatment at the fifth session were randomly allocated (n=57) to either CBT and DCS or CBT and placebo.ResultsYouth in the CBT and DCS group had significant reductions in symptoms, but these reductions were not greater than those in the CBT and placebo group. There was a trend toward DCS speeding PTSD symptom recovery during the exposure-based sessions, and evidence that the CBT and DCS group better maintained stability of gains on inattention ratings from posttreatment to the 3 month follow-up.ConclusionsThis initial study of CBT and DCS to treat pediatric PTSD provided suggestive and preliminary evidence for more rapid symptom recovery and beneficial effects on attention, but did not show an overall greater effect for reducing PTSD symptoms. It appears that augmentation with DCS represents unique challenges in PTSD. Because PTSD involves complex, life-threatening trauma memories, as opposed to the imagined dreadful outcomes of other anxiety disorders, the use of DCS may require greater attention to how its use is coupled with exposure-based techniques. DCS may have inadvertently enhanced reconsolidation of trauma memories rather than more positive and adaptive memories. In addition, the results suggest that future research could focus on the longer-term benefits of DCS on attention and ways to capitalize on attention-enhancing therapies. ClinicalTrials.gov registry: Effect of D-cycloserine on Treatment of Posttraumatic Stress Disorder (PTSD) in Youth, #NCT01157416, http://clinicaltrials.gov/ct2/results?term=NCT01157416&Search=Search , and D-cycloserine Adjunctive Treatment for Posttraumatic Stress Disorder (PTSD) in Adolescents, #NCT01157429, http://clinicaltrials.gov/ct2/results?term=NCT01157429&Search=Search .

Project description:Importance:Internet-delivered cognitive behavior therapy is an effective treatment for children and adolescents with obsessive-compulsive disorder and has the potential to markedly increase access to treatment for patients while being cost-effective for health care organizations. Objective:To investigate whether internet-delivered cognitive behavior therapy implemented within a stepped care model is noninferior to, and cost-effective compared with, the gold standard of face-to-face cognitive behavior therapy for pediatric obsessive-compulsive disorder. Design, Setting, and Participants:Multicenter, single-blind, randomized clinical noninferiority trial implemented at 2 specialist pediatric obsessive-compulsive disorder clinics in Stockholm and Gothenburg, Sweden. Participants are 152 children and adolescents aged 7 to 17 years with obsessive compulsive disorder, recruited through the 2 clinics and online self-referral. Patients will be randomized 1:1 to the stepped care intervention or face-to-face therapy. Blind evaluations will be conducted after treatment and at 3-month and 6-month follow-ups. At the 6-month follow-up (primary end point), noninferiority will be tested and resource use will be compared between the 2 treatment groups. Data will be analyzed according to intention-to-treat principles. Intervention:Patients randomized to stepped care will first receive internet-delivered cognitive behavior therapy for 16 weeks; patients who are classified as nonresponders 3 months after treatment completion will receive additional face-to-face therapy. The control group will receive 16 weeks of face-to-face cognitive behavior therapy immediately following randomization and nonresponders at the 3-month follow-up will, as in the stepped care group, receive additional face-to-face therapy. Main Outcomes and Measures:Noninferiority is defined as a 4-point difference on the primary outcome measure (Children's Yale-Brown Obsessive Compulsive Scale). Discussion:Recruitment started October 6, 2017, and was completed May 24, 2019. Results from the primary end point will be available by May 2020. The naturalistic follow-ups (1, 2, and 5 years after the end of treatment) will continue to 2025. There are no interim analyses planned or stopping rules for the trial. Trial Registration:ClinicalTrials.gov identifier: NCT03263546.

Dataset Information

Efficacy of Augmentation of Cognitive Behavior Therapy With Weight-Adjusted d-Cycloserine vs Placebo in Pediatric Obsessive-Compulsive Disorder: A Randomized Clinical Trial.

Publications

Efficacy of Augmentation of Cognitive Behavior Therapy With Weight-Adjusted d-Cycloserine vs Placebo in Pediatric Obsessive-Compulsive Disorder: A Randomized Clinical Trial.

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