D-cycloserine does not enhance exposure-response prevention therapy in obsessive-compulsive disorder

Department of Psychiatry, University of Florida, Gainesville, Florida, United States
International Clinical Psychopharmacology (Impact Factor: 2.46). 08/2007; 22(4):230-7. DOI: 10.1097/YIC.0b013e32819f8480
Source: PubMed

ABSTRACT Obsessive-compulsive disorder is a common, chronic, and oftentimes disabling disorder. The only established first-line treatments for obsessive-compulsive disorder are exposure and response prevention therapy and the serotonin reuptake inhibitors. Many patients do not experience complete symptom resolution with either modality and require augmentation approaches. Recent animal and clinical data suggest that D-cycloserine, a partial agonist that acts at the strychnine-insensitive glycine-recognition site of the N-methyl-D-aspartate receptor complex, may enhance extinction learning that occurs in exposure-based psychotherapies. Given this, this study examined if D-cycloserine (250 mg) enhances the overall efficacy and rate of change of exposure and response prevention therapy for adult obsessive-compulsive disorder. Participants were 24 adults meeting Diagnostic and Statistical Manual of Mental Disorders-IV criteria for obsessive-compulsive disorder. The study design was a randomized, double-blinded, placebo-controlled augmentation trial examining exposure and response prevention therapy+D-cycloserine versus exposure and response prevention therapy+placebo. All patients received 12 weekly sessions of exposure and response prevention treatment. The first session involved building a ritual hierarchy and providing psychoeducation about obsessive-compulsive disorder. The second session involved a practice exposure. Sessions 3-12 involved exposure and response prevention exercises. D-cycloserine or placebo (250 mg) was taken 4 h before every session. No significant group differences were found across outcome variables. The rate of improvement did not differ between groups. The present results fail to support the use of D-cycloserine with exposure and response prevention therapy for adult obsessive-compulsive disorder. As this study is the first to explore this question and a number of methodological issues must be considered when interpreting the findings, the conclusions that may be drawn from our results are limited.

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    • "Several studies have supported DCS augmentation of exposure-based psychotherapy with a putative mechanism of enhancing fear extinction learning during exposure sessions for adults with acrophobia (Ressler et al. 2004), social phobia (Guastella et al. 2008; Hofmann et al. 2006) and panic disorder (Otto et al. 2010). There are three published studies regarding DCS augmented E/RP in adult OCD (Kushner et al. 2007; Storch et al. 2007c; Wilhelm et al. 2008) and one in pediatric OCD (Storch et al. 2010a, b). All studies were randomized, double-blind, and placebo-controlled . "
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    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
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    • "ogical enhancers include D - cycloserine , and Yohimbine hydrochloride . Although there are some studies demonstrat - ing that D - cycloserine ( Bontempo et al . , 2012 ; Norberg et al . , 2008 ) and Yohimbine hydrochloride ( Powers et al . , 2009 ) may indeed enhance extinction in exposure therapy , results of other studies are negative ( e . g . Storch et al . , 2007 ; Litz et al . , 2012 ; Meyerbröker et al . , 2013 ) . Further studies are needed to investigate the potential of cognitive enhancers in the context of exposure therapies ."
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    ABSTRACT: Psychological models of mental disorders guide research into psychological and environmental factors that elicit and maintain mental disorders as well as interventions to reduce them. This paper addresses four areas. (1) Psychological models of mental disorders have become increasingly transdiagnostic, focusing on core cognitive endophenotypes of psychopathology from an integrative cognitive psychology perspective rather than offering explanations for unitary mental disorders. It is argued that psychological interventions for mental disorders will increasingly target specific cognitive dysfunctions rather than symptom-based mental disorders as a result. (2) Psychotherapy research still lacks a comprehensive conceptual framework that brings together the wide variety of findings, models and perspectives. Analysing the state-of-the-art in psychotherapy treatment research, "component analyses" aiming at an optimal identification of core ingredients and the mechanisms of change is highlighted as the core need towards improved efficacy and effectiveness of psychotherapy, and improved translation to routine care. (3) In order to provide more effective psychological interventions to children and adolescents, there is a need to develop new and/or improved psychotherapeutic interventions on the basis of developmental psychopathology research taking into account knowledge of mediators and moderators. Developmental neuroscience research might be instrumental to uncover associated aberrant brain processes in children and adolescents with mental health problems and to better examine mechanisms of their correction by means of psychotherapy and psychological interventions. (4) Psychotherapy research needs to broaden in terms of adoption of large-scale public health strategies and treatments that can be applied to more patients in a simpler and cost-effective way. Increased research on efficacy and moderators of Internet-based treatments and e-mental health tools (e.g. to support "real time" clinical decision-making to prevent treatment failure or relapse) might be one promising way forward. Copyright © 2013 John Wiley & Sons, Ltd.
    International Journal of Methods in Psychiatric Research 01/2014; 23(1):58-91. DOI:10.1002/mpr.1411 · 3.76 Impact Factor
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    • "Patients who used antidepressants were not excluded in both PTSD trials, but they were required to be on a stable dose prior to enrollment. In lab-rats it was found that DCS did not facilitate extinction learning in rats previously exposed to the tricyclic antidepressant imipramine (Werner-Seidler & Richardson, 2007), but no evidence was found for negative interaction effects between antidepressant medication and DCS enhancement effects in patients with PTSD (de Kleine et al., 2012) or other anxiety disorders (Hofmann et al., 2006; Kushner et al., 2007; Storch et al., 2007). "
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    ABSTRACT: There is a good amount of evidence that exposure therapy is an effective treatment for posttraumatic stress disorder (PTSD). Notwithstanding its efficacy, there is room for improvement, since a large proportion of patients does not benefit from treatment. Recently, an interesting new direction in the improvement of exposure therapy efficacy for PTSD emerged. Basic research found evidence of the pharmacological enhancement of the underlying learning and memory processes of exposure therapy. The current review aims to give an overview of clinical studies on pharmacological enhancement of exposure-based treatment for PTSD. The working mechanisms, efficacy studies in PTSD patients, and clinical utility of four different pharmacological enhancers will be discussed: d-cycloserine, MDMA, hydrocortisone, and propranolol.
    European Journal of Psychotraumatology 10/2013; 4. DOI:10.3402/ejpt.v4i0.21626 · 2.40 Impact Factor
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