Augmentation of Behavior Therapy With d -Cycloserine for Obsessive-Compulsive Disorder

Harvard University, Cambridge, Massachusetts, United States
American Journal of Psychiatry (Impact Factor: 12.3). 04/2008; 165(3):335-41; quiz 409. DOI: 10.1176/appi.ajp.2007.07050776
Source: PubMed


This study examined whether d-cycloserine, a partial agonist at the N-methyl-D-aspartate (NMDA) glutamatergic receptor, enhances the efficacy of behavior therapy for obsessive-compulsive disorder (OCD).
A randomized, double-blind, placebo-controlled trial investigating D-cycloserine versus placebo augmentation of behavior therapy was conducted in 23 OCD patients. Patients first underwent a diagnostic interview and pretreatment evaluation, followed by a psychoeducational/treatment planning session. Then they received 10 behavior therapy sessions. Treatment sessions were conducted twice per week. One hour before each of the behavior therapy sessions, the participants received either D-cycloserine, 100 mg, or a placebo.
Relative to the placebo group, the D-cycloserine group's OCD symptoms were significantly more improved at mid-treatment, and the D-cycloserine group's depressive symptoms were significantly more improved at posttreatment.
These data provide support for the use of D-cycloserine as an augmentation of behavior therapy for OCD and extend findings in animals and other human disorders suggesting that behavior therapy acts by way of long-term potentiation of glutamatergic pathways and that the effects of behavior therapy are potentiated by an NMDA agonist.

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Available from: David F Tolin, Nov 10, 2015
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    • "Recent evidence raises the possibility that DCS may not increase the benefit received from participation in psychosocial interventions, but instead may help individuals achieve this benefit more quickly (Siegmund et al. 2011; Kushner et al. 2007; Wilhelm et al. 2008; Chasson et al. 2010). Thus, to assess the rate of improvement in cognitive functioning, participants will complete the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS: (Randolph 1998)). "
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    ABSTRACT: Background Cognitive remediation (CR) has shown significant promise in addressing the cognitive deficits that accompany serious mental illness. However, this intervention does not appear to completely ameliorate the cognitive deficits that accompany these illnesses. D-cycloserine (DCS), an NMDA receptor partial agonist, has been shown to enhance the therapeutic benefits of learning-based psychosocial interventions for psychiatric disorders. Thus, the goal of this study is to examine the utility of combining cognitive remediation and d-cycloserine in the treatment of cognitive deficits among individuals with bipolar disorder. Methods/Design Approximately forty individuals with bipolar disorder will be recruited to participate in this study. Participants will be randomized to one of two study arms: CR + DCS or CR + placebo. The primary outcome for this study is change in cognitive functioning. We will also examine several secondary outcomes, including the rate of change of cognitive functioning, social functioning, and symptomatology. Discussion Cognitive deficits are a rate-limiting factor in functional recovery among individuals with bipolar disorder. Unfortunately, treatment options for these deficits are limited. The results of the proposed study may reveal a valuable intervention strategy (i.e., CR with concurrent DCS) to improve cognitive functioning among individuals with bipolar disorder. Ultimately, this treatment strategy may prove useful in addressing the cognitive deficits that are ubiquitous across serious mental illnesses. Trial registration NCT01934972.
    Full-text · Article · Oct 2014 · BMC Psychology
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    • "Dosing was based according to weight; children who weighed between 25–45 kg were given 25 mg of DCS or placebo and children weighing C45 were given 50 mg of DCS or placebo (2 capsules were administered). Dosages used were derived from findings from previous adult studies that indicated that approximately 0.7 mg/kg was the most effective (Hofmann et al. 2006; Otto et al. 2010; Ressler et al. 2004; Wilhelm et al. 2008). Time of dosing was determined based off of previous studies, which noted that with a 10-h half life, 50 mg of DCS is estimated to reach peak cerebrospinal fluid levels within 1–2 h of administration (Hofmann et al. 2006; Nair et al.1956; Ressler et al. 2004). "
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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.
    Full-text · Article · Jul 2014 · Journal of Child and Family Studies
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    • "The study by Wilhelm and colleagues [62] reported that although symptoms decreased for both groups, they were significantly lower in the DCS group than the control group at mid-treatment, but not at post-treatment. A re-analysis of these results [63] showed that treatment effects of exposure and response prevention were almost six times faster in the DCS group during the first half of treatment. "
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    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.
    Full-text · Article · Jun 2013 · Biology of Mood and Anxiety Disorders
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