Article

Need for speed: Evaluating slopes of OCD recovery in behavior therapy enhanced with D-cycloserine

Massachusetts General Hospital/Harvard Medical School, Boston, MA 02114, USA.
Behaviour Research and Therapy (Impact Factor: 3.85). 03/2010; 48(7):675-9. DOI: 10.1016/j.brat.2010.03.007
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ABSTRACT Evidence suggests that the antibiotic d-cycloserine (DCS) enhances the treatment effects of exposure and response prevention (ERP) for Obsessive-Compulsive Disorder (OCD). Further, evidence suggests that the effects of DCS diminish partway through treatment, but it is unclear to what extent. In an effort to evaluate these issues, the current study re-analyzes data from a 10-session randomized controlled trial of ERP+DCS versus ERP+placebo in a sample of 22 adults with OCD. We analyzed repeated-measures mixed models with random slopes and intercepts across different intervals: sessions 1-10, 1-5, and 6-10. The results indicate that the course of ERP was 2.3 times faster over the full 10 sessions for the DCS compared to the placebo group, and nearly six times quicker in the first half of ERP. Further interpretation of the results suggests that DCS does not amplify the effects of ERP, but instead initiates treatment effects sooner in treatment. In addition, DCS does not necessarily lose its effect over repeated use, but instead may exhaust its maximum utility after effectively jump-starting ERP. Ultimately, DCS may provide a means for curtailing treatment costs, decreasing treatment dropout and refusal rates, and enhancing access to care.

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Available from: Ulrike Buhlmann, Jul 29, 2015
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    • "Given the focus on exposure processes in the current study, we randomly selected two sessions from the early exposure phase (sessions 4–7) and two sessions from the later exposure phase (sessions 8–12). This approach is supported by research showing slope differences between exposures early and later in treatment (Chasson et al., 2010). Less than four sessions were coded only if the case had insufficient videotapes available, due to early termination from therapy, equipment malfunction, or exposures occurred outside therapy room. "
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    ABSTRACT: Behavioral engagement and cognitive coping have been hypothesized to mediate effectiveness of exposure-based therapies. Identifying which specific child factors mediate successful therapy and which therapist factors facilitate change can help make our evidence-based treatments more efficient and robust. The current study examines the specificity and temporal sequence of relations among hypothesized client and therapist mediators in exposure therapy for pediatric Obsessive Compulsive Disorder (OCD). Youth coping (cognitive, behavioral), youth safety behaviors (avoidance, escape, compulsive behaviors), therapist interventions (cognitive, exposure extensiveness), and youth anxiety were rated via observational ratings of therapy sessions of OCD youth (N=43; ages=8 - 17; 62.8% male) who had received Exposure and Response Prevention (ERP). Regression analysis using Generalized Estimation Equations and cross-lagged panel analysis (CLPA) were conducted to model anxiety change within and across sessions, to determine formal mediators of anxiety change, and to establish sequence of effects. Anxiety ratings decreased linearly across exposures within sessions. Youth coping and therapist interventions significantly mediated anxiety change across exposures, and youth-interfering behavior mediated anxiety change at the trend level. In CLPA, youth-interfering behaviors predicted, and were predicted by, changes in anxiety. Youth coping was predicted by prior anxiety change. The study provides a preliminary examination of specificity and temporal sequence among child and therapist behaviors in predicting youth anxiety. Results suggest that therapists should educate clients in the natural rebound effects of anxiety between sessions and should be aware of the negatively reinforcing properties of avoidance during exposure. Copyright © 2015. Published by Elsevier Ltd.
    Behavior Therapy 02/2015; 46(3). DOI:10.1016/j.beth.2015.01.003 · 2.43 Impact Factor
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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 ClinicalTrials.gov NCT01934972.
    10/2014; 2(1):41. DOI:10.1186/s40359-014-0041-4
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    • "E/RP group reached a decrease of more than 50 % reduction of subjective units of distress scale two sessions more quickly than those in the placebo group. Wilhelm et al. (2008) found that those who received 100 mg of DCS 1 h prior to each E/RP session had significantly lower OCD severity scores than the placebo group (Cohen's d = 0.63) after five exposure sessions relative to those in the placebo group, suggesting that DCS significantly increased the pace of symptom reduction in those with OCD (Chasson et al. 2010). Storch et al. (2007a, b, c) (n = 24) did not find significant differences in OCD severity at post-treatment or follow up between the DCS ? "
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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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