A Preliminary Study of D-Cycloserine Augmentation of Cognitive-Behavioral Therapy in Pediatric Obsessive-Compulsive Disorder

Department of Pediatrics and Psychiatry, Rothman Center for Neuropsychiatry, University of South Florida, St. Petersburg, FL 33701, USA.
Biological psychiatry (Impact Factor: 10.26). 12/2010; 68(11):1073-6. DOI: 10.1016/j.biopsych.2010.07.015
Source: PubMed


Research on the neural circuitry underlying fear extinction has led to the examination of D-cycloserine (DCS), a partial agonist at the N-methyl-D-aspartate receptor in the amygdala, as a method to enhance exposure therapy outcome. Preliminary results have supported the use of DCS to augment exposure therapy in adult anxiety disorders; however, no data have been reported in any childhood anxiety disorder. Thus, we sought to preliminarily examine whether weight-adjusted DCS doses (25 or 50 mg) enhanced the overall efficacy of cognitive-behavioral therapy (CBT) for pediatric obsessive-compulsive disorder (OCD).
Participants were 30 youth (aged 8-17) with a primary diagnosis of OCD. The study design was a randomized, double-blinded, placebo-controlled augmentation trial examining CBT + DCS versus CBT + Placebo (15 youth per group). All patients received seven exposure and response prevention sessions paired with DCS or placebo taken 1 hour before sessions.
Although not significantly different, compared with the CBT + Placebo group, youth in the CBT + DCS arm showed small-to-moderate treatment effects (d = .31-.47 on primary outcomes). No adverse events were recorded.
These results complement findings in adult OCD and non-OCD anxiety disorders and provide initial support for a more extensive study of DCS augmentation of CBT among youth with OCD.

Download full-text


Available from: Aude Henin,
  • Source
    • "The CY-BOCS has demonstrated good psychometric properties (e.g. inter-rater reliability, internal consistency, test–retest reliability, discriminant validity, convergent validity; (Scahill et al. 1997; Storch et al. 2004). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Clinical studies in adults and children with obsessive–compulsive disorder (OCD) have shown that d-cycloserine (DCS) can improve treatment response by enhancing fear extinction learning during exposure-based psychotherapy. Some have hypothesized that improved treatment response is a function of increased compliance and engagement in therapeutic homework tasks, a core component of behavioral treatment. The present study examined the relationship between DCS augmented cognitive-behavioral therapy (CBT) and homework compliance in a double-blind, placebo controlled trial with 30 youth with OCD. All children received 10 CBT sessions, the last seven of which included exposure and response prevention paired with DCS or placebo dosed 1 h before the session started. Results suggested that DCS augmented CBT did not predict improved homework compliance over the course of treatment, relative to the placebo augmented CBT group. However, when groups were collapsed, homework compliance was directly associated with treatment outcome. These findings suggest that while DCS may not increase homework compliance over time, more generally, homework compliance is an integral part of pediatric OCD treatment outcome.
    Journal of Child and Family Studies 07/2014; 23(5). DOI:10.1007/s10826-013-9742-1 · 1.42 Impact Factor
  • Source
    • "One promising avenue involves d-cycloserine (DCS) augmentation of ERP. Preliminary results have been promising, demonstrating an advantage for DCS augmentation or ERP relative to placebo (Storch et al., 2010). Beyond the overall treatment effects, this approach may accelerate the rate of response (Chasson et al., 2010) and, importantly, do so in a very safe manner that is acceptable to parents. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Obsessive-compulsive disorder (OCD) has long been considered a complex and disabling psychiatric condition, marked by intrusive and unwanted imagery (obsessions) that is usually accompanied by ritualized behavior designed to neutralize the obsessions. Treatment research has shown that, for those who complete treatment, significant improvement can be achieved (Simpson et al., 2011; Storch, Geffken, et al., 2007). There is a growing consensus that the first-line psychosocial treatment for OCD is exposure with response prevention (ERP; McKay et al., 2013; Olatunji et al., 2013). In the case of children, meta-analyses have shown that ERP is highly efficacious, with large effect sizes (mean d = 1.98; Abramowitz, Whiteside, & Deacon, 2005). Indeed, practice parameters recommend ERP monotherapy as the treatment of choice for mild and moderate cases, and together with antidepressant medication for only the most severe presentation. Although this augurs well for the treatment of children with OCD, not all children respond to treatment and ERP dissemination remains a challenge. Accordingly, this special issue is devoted to cases involving variations in treatment delivery and symptom presentation in childhood OCD. The articles that form this special issue address a variety of special circumstances that take the reader beyond the findings from randomized controlled trials that evaluate the efficacy of ERP in general. Instead, these cases help the reader understand the issue of comorbidity and how to successfully contend with it during treatment, and provide a peek at several promising avenues that are emerging in the treatment of childhood OCD. These include addressing family-related complications in treatment delivery, specific developmental phases (i.e., in very young children), Also examined in this special are cases with under severe stigmatizing conditions, when symptoms present with complex comorbidities, and evaluation of interventios that by capitalizes on technological advances in service delivery.
    Clinical Case Studies 12/2013; 13(1):3-8. DOI:10.1177/1534650113504486
  • Source
    • "Notably, the design of this study is significantly different than the other DCS trials because the dosage, which was relatively high, was administered 4 hours instead of the more common 1 or 2 hours before CBT sessions. The pediatric obsessive-compulsive disorder trial [66] reported that the DCS-augmented CBT group showed small-to-moderate treatment effects over the CBT plus placebo group. However, these effects did not reach the level of statistical significance. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The goal of this review is to examine the clinical studies on d-cycloserine, a partial glutamatergic N-methyl-D-aspartate agonist, as an augmentation strategy for exposure procedures during cognitive behavioral therapy for anxiety disorders. Although cognitive behavioral therapy and anxiolytic medications are more effective than placebo for treating anxiety disorders, there is still considerable room for further improvement. Traditional combination strategies typically yield disappointing results. However, recent studies based on translational research have shown promise to augment the neural circuitry underlying fear extinction with pharmacological means. We discuss the current state of the literature, including inconsistencies of findings and issues concerning the drug mechanism, dosing, and dose timing. D-cycloserine is a promising combination strategy for cognitive behavioral therapy of anxiety disorders by augmenting extinction learning. However, there is also evidence to suggest that d-cycloserine can facilitate reconsolidation of fear memory when exposure procedures are unsuccessful.
    Biology of Mood and Anxiety Disorders 06/2013; 3(1):11. DOI:10.1186/2045-5380-3-11
Show more