D-cycloserine does not enhance exposure-response prevention therapy in obsessive-compulsive disorder
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.
- SourceAvailable from: apt.rcpsych.org[Show abstract] [Hide abstract]
ABSTRACT: Pharmacological strategies for the treatment of obsessive-compulsive disorder (OCD) continue to develop apace but deficiencies remain. We present an updated literature review of the evidence supporting available strategies. We aim to answer key questions including: (1) What are the first-line treatments? (2) Does pharmacotherapy improve health-related quality of life? (3) How do we evaluate clinical response and relapse? (4) How long should treatment continue? (5) Can we predict treatment outcomes? (6) What is the management of treatment-refractory OCD? Selective serotonin reuptake inhibitors (SSRIs) remain the pharmacological treatment of choice for most patients and are associated with improved health-related quality of life. However, discontinuation is associated with relapse and loss of quality of life, implying treatment should continue long term. A substantial minority of patients fail to respond to SSRI. Such patients may respond to strategies such as dose elevation or adjunctive antipsychotic, although long-term trials validating the effectiveness and tolerability of these strategies are relatively lacking. Newer compounds targeting other neurotransmitter systems, such as glutamate, are undergoing evaluation.The International Journal of Neuropsychopharmacology 01/2012; 15(8):1173-91. DOI:10.1017/S1461145711001829 · 5.26 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: To evaluate the overall effect of D-cycloserine (DCS) augmentation on exposure and response prevention (ERP) therapy for obsessive-compulsive disorder (OCD). Clinical studies on the effect of DCS augmentation on ERP therapy for OCD compared to placebo were included for meta analysis. The primary outcome was the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Meta-analyses were performed with a random-effect model or a fixed-effect model using the Cochrane Review Manager (RevMan, version 5.2) to calculate the odds ratio and the mean difference, with their corresponding 95% confidence intervals. A total of six studies was included in the current meta-analyses, and their data were extracted. Among them, four were for analyses of DCS and Y-BOCS at midtreatment, six for analysis at posttreatment, and four at 3-month follow-up. Besides, three of the six eligible studies were included in the meta-analysis of the DCS and Clinical Global Impression-Severity Scale at posttreatment, and three in the meta-analysis of DCS and proportions of treatment responders and of subjects attaining clinical remission status criteria at posttreatment. Our meta-analyses do not reveal a significant effect of DCS augmentation in ERP therapy for OCD patients, except when measured at midtreatment. Compared to the placebo group, DCS augmentation did show a trend toward significantly lower/decreased Y-BOCS; when measured at posttreatment and in the subpopulation of DCS taken before some of the ERP sessions, DCS augmentation showed a trend toward significantly lower/decreased Y-BOCS. Our result suggested that with the careful optimization of DCS-augmented ERP therapy by fine-tuning timing and dosing of DCS administration and number and frequency of ERP sessions, DCS may enhance the efficacy of ERP therapy in reducing the symptomatic severity of OCD patients, especially at early stage of the treatment; therefore, DCS augmentation could possibly reduce treatment cost, reduce treatment drop and refusal rate, and help to improve access to the limited number of experienced therapists.Drug Design, Development and Therapy 01/2015; 9:2101-17. DOI:10.2147/DDDT.S68994 · 3.03 Impact Factor
- International handbook for anxiety disorders. Volume 2., Edited by P. Emmelkamp and T. Ehring, 01/2013: chapter Exposure therapy for anxiety disorders: Procedural variations, clinical efficacy, and change mechanisms.; Wiley-Blackwell..