Does d-cycloserine facilitate the effects of homework compliance on social anxiety symptom reduction?

BACKGROUND: Prior studies examining the effect of d-cycloserine (DCS) on homework compliance and outcome in cognitive-behavior therapy (CBT) have yielded mixed results. The aim of this study was to investigate whether DCS facilitates the effects of homework compliance on symptom reduction in a large-scale study for social anxiety disorder (SAD). METHODS: 169 participants with generalized SAD received DCS or pill placebo during 12-session exposure-based group CBT. Improvements in social anxiety were assessed by independent raters at each session using the Liebowitz social anxiety scale (LSAS). RESULTS: Controlling for LSAS at the previous session, and irrespective of treatment condition, greater homework compliance in the week prior related to lower LSAS at the next session. However, DCS did not moderate the effect of homework compliance and LSAS, LSAS on homework compliance, or the overall augmenting effect of DCS on homework compliance. Furthermore, LSAS levels were not predictive of homework compliance in the following week. CONCLUSION: The findings support the general benefits of homework compliance on outcome, but not a DCS-augmenting effect. The comparably small number of DCS-enhanced sessions in this study could be one reason for the failure to find a facilitating effect of DCS

Enhancement of psychosocial treatment with D-cycloserine: models, moderators, and future directions

Advances in the understanding of the neurobiology of fear extinction have resulted in the development of d-cycloserine (DCS), a partial glutamatergic N-methyl-D-aspartate agonist, as an augmentation strategy for exposure treatment. We review a decade of research that has focused on the efficacy of DCS for augmenting the mechanisms (e.g., fear extinction) and outcome of exposure treatment across the anxiety disorders. Following a series of small-scale studies offering strong support for this clinical application, more recent larger-scale studies have yielded mixed results, with some showing weak or no effects. We discuss possible explanations for the mixed findings, pointing to both patient and session (i.e., learning experiences) characteristics as possible moderators of efficacy, and offer directions for future research in this area. We also review recent studies that have aimed to extend the work on DCS augmentation of exposure therapy for the anxiety disorders to DCS enhancement of learning-based interventions for addiction, anorexia nervosa, schizophrenia, and depression. Here, we attend to both DCS effects on facilitating therapeutic outcomes and additional therapeutic mechanisms beyond fear extinction (e.g., appetitive extinction, hippocampal-dependent learning).F31 MH103969 - NIMH NIH HHS; K24 DA030443 - NIDA NIH HHS; R34 MH099309 - NIMH NIH HHS; R34 MH086668 - NIMH NIH HHS; R21 MH102646 - NIMH NIH HHS; R34 MH099318 - NIMH NIH HH

Effect of d-cycloserine on fear extinction training in adults with social anxiety disorder

© 2019 Hofmann et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Preclinical and clinical data have shown that D-cycloserine (DCS), a partial agonist at the N-methyl-d-aspartate receptor complex, augments the retention of fear extinction in animals and the therapeutic learning from exposure therapy in humans. However, studies with nonclinical human samples in de novo fear conditioning paradigms have demonstrated minimal to no benefit of DCS. The aim of this study was to evaluate the effects of DCS on the retention of extinction learning following de novo fear conditioning in a clinical sample. Eighty-one patients with social anxiety disorder were recruited and underwent a previously validated de novo fear conditioning and extinction paradigm over the course of three days. Of those, only 43 (53%) provided analyzable data. During conditioning on Day 1, participants viewed images of differently colored lamps, two of which were followed by with electric shock (CS+) and a third which was not (CS-). On Day 2, participants were randomly assigned to receive either 50 mg DCS or placebo, administered in a double-blind manner 1 hour prior to extinction training with a single CS+ in a distinct context. Day 3 consisted of tests of extinction recall and renewal. The primary outcome was skin conductance response to conditioned stimuli, and shock expectancy ratings were examined as a secondary outcome. Results showed greater skin conductance and expectancy ratings in response to the CS+ compared to CS- at the end of conditioning. As expected, this difference was no longer present at the end of extinction training, but returned at early recall and renewal phases on Day 3, showing evidence of return of fear. In contrast to hypotheses, DCS had no moderating influence on skin conductance response or expectancy of shock during recall or renewal phases. We did not find evidence of an effect of DCS on the retention of extinction learning in humans in this fear conditioning and extinction paradigm

D-cycloserine augmentation of exposure-based cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders: a systematic review and meta-analysis of individual participant data

Importance: Whether and under which conditions D-cycloserine (DCS) augments the effects of exposure-based cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders is unclear. Objective: To clarify whether DCS is superior to placebo in augmenting the effects of cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders and to evaluate whether antidepressants interact with DCS and the effect of potential moderating variables. Data Sources: PubMed, EMBASE, and PsycINFO were searched from inception to February 10, 2016. Reference lists of previous reviews and meta-analyses and reports of randomized clinical trials were also checked. Study Selection: Studies were eligible for inclusion if they were (1) double-blind randomized clinical trials of DCS as an augmentation strategy for exposure-based cognitive behavior therapy and (2) conducted in humans diagnosed as having specific phobia, social anxiety disorder, panic disorder with or without agoraphobia, obsessive-compulsive disorder, or posttraumatic stress disorder. Data Extraction and Synthesis: Raw data were obtained from the authors and quality controlled. Data were ranked to ensure a consistent metric across studies (score range, 0-100). We used a 3-level multilevel model nesting repeated measures of outcomes within participants, who were nested within studies. Results: Individual participant data were obtained for 21 of 22 eligible trials, representing 1047 of 1073 eligible participants. When controlling for antidepressant use, participants receiving DCS showed greater improvement from pretreatment to posttreatment (mean difference, -3.62; 95% CI, -0.81 to -6.43; P = .01; d = -0.25) but not from pretreatment to midtreatment (mean difference, -1.66; 95% CI, -4.92 to 1.60; P = .32; d = -0.14) or from pretreatment to follow-up (mean difference, -2.98, 95% CI, -5.99 to 0.03; P = .05; d = -0.19). Additional analyses showed that participants assigned to DCS were associated with lower symptom severity than those assigned to placebo at posttreatment and at follow-up. Antidepressants did not moderate the effects of DCS. None of the prespecified patient-level or study-level moderators was associated with outcomes. Conclusions and Relevance: D-cycloserine is associated with a small augmentation effect on exposure-based therapy. This effect is not moderated by the concurrent use of antidepressants. Further research is needed to identify patient and/or therapy characteristics associated with DCS response.2018-05-0

Physical Activity and Community Engagement (PACE) to facilitate community reintegration among returning veterans: Study protocol for a randomized controlled trial

There is a surprising lack of disseminable, community-based interventions for veterans experiencing difficulties during the reintegration process from military to civilian life. Physical Activity and Community Engagement (PACE) is a program which combines routine vigorous-intensity exercise with community engagement. The program builds on emergent evidence supporting the benefits of routine vigorous-intensity exercise among and establishing social connection. Using a randomized controlled trial (N = 60), we will obtain feasibility data and initial effect sizes for the early effects of PACE on reintegration difficulties

Targeting Anxiety Sensitivity With Evidence-Based Psychoeducation: A Randomized Waitlist-Controlled Trial of a Brief Standalone Digital Intervention

Anxiety sensitivity, or the fear of anxiety, represents an important transdiagnostic target in the prevention and treatment of anxiety disorders, which typically emerge between childhood and early adulthood. Recent work demonstrated that single-session digital psychoeducation interventions delivered on computers in a lab setting can effectively reduce anxiety sensitivity. This evidence suggests that digital psychoeducation interventions have potential as a scalable and cost-effective approach to targeting anxiety sensitivity in emerging adults. Toward this aim, we developed the Anxiety Insight Modules (AIM), which promote insights about the function of anxiety, the activating role of thoughts, the harmless nature of sensations that often co-occur with anxiety, and the negative impact of trying to avoid anxiety. To facilitate a more accurate estimate of the potential for scalability, participants tested AIM on their personal devices at their preferred schedule and pace without the involvement of clinicians or staff. Undergraduate students with high levels of anxiety sensitivity (N = 159) were randomized to gain immediate access to AIM (n = 77) or to a waitlist control that gained access to AIM after the 2-week follow-up assessment (n = 82). All of the participants who gained immediate access to AIM, as well as 91.67% of participants in the waitlist who participated in the follow-up, completed the full set of modules, suggesting high levels of engagement. Immediate access to AIM had a medium-to-large effect on anxiety sensitivity in a 2-week follow-up comparison with waitlist control (d = 0.57–0.76). Participants that completed AIM showed acute reductions in anxiety sensitivity. Given this preliminary evidence of its effectiveness, further research is warranted to determine the factors that moderate and mediate AIM's impact on anxiety sensitivity in order to optimize its delivery and facilitate scalability.24 month embargo; available online: 30 April 2022This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Anxiety Sensitivity and Working Memory Capacity: Risk Factors and Targets for Health Behavior Promotion

Understanding the nature and influence of specific risk profiles is increasingly important for health behavior promotion. The purpose of this article is to document the value of two factors—anxiety sensitivity (AS) and working memory capacity (WMC)—for enhancing risk for the initiation and/or maintenance of a range of negative health behaviors. AS is a distress-related risk factor that potentiates avoidance/coping motivations for negative health behaviors. Stress provides the conditions for negative somatic and affective states, and AS amplifies the aversiveness of these experiences and correspondingly hinders adaptive functioning. In contrast, low WMC is hypothesized to exert its effect by decreasing the capacity to filter out current temptations, attenuating a focus on longer-term goals and impairing the application of relevant coping skills at times of stress. In this review, we provide conceptual models for the separate roles of high AS and low WMC in negative health behaviors, review the influence of these factors on specific health behavior exemplars (eating behaviors/obesity, physical activity, smoking, alcohol use, and sleep promotion), provide preliminary evidence for their value as independent treatment targets for health-behavior promotion, and encourage specific research directions in relation to these variables

Effects of anxiety sensitivity reduction on smoking abstinence: An analysis from a panic prevention program

© 2018 American Psychological Association. Objective: Scientific evidence implicates anxiety sensitivity (AS) as a risk factor for poor smoking cessation outcomes. Integrated smoking cessation programs that target AS may lead to improved smoking cessation outcomes, potentially through AS reduction. Yet, little work has evaluated the efficacy of integrated smoking cessation treatment on smoking abstinence. The present study prospectively examined treatment effects of a novel AS reduction-smoking cessation intervention relative to a standard smoking cessation intervention on smoking abstinence. Method: Participants (N = 529; 45.9% male; M age = 38.23, SD = 13.56) included treatment-seeking smokers who received either a 4-session integrated anxiety-reduction and smoking cessation intervention (Smoking Treatment and Anxiety Management Program; [STAMP]) or a 4-session standard smoking cessation program (SCP). The primary aims focused on examining the effects of STAMP on (a) AS reduction during treatment, (b) early and late smoking point prevalence abstinence, and (c) the mechanistic function of AS reduction on treatment effects across early and late smoking abstinence. Results: Results indicated a significantly greater decline in AS in STAMP relative to SCP (B = -.72, p \u3c .001). Treatment condition did not significantly directly predict early or late abstinence. However, the effect of STAMP on early abstinence was significantly mediated by reductions in AS (indirect = .16, 95% CI [.02, .40]). Conclusions: Findings provide evidence for the efficacy of a novel, integrated anxiety and smoking cessation treatment to reduce AS. Moreover, the meditation pathway from STAMP to early abstinence through reductions in AS suggest that AS is a clinically important mechanism of change for smoking cessation treatment and research

Psychological and pharmacological treatments for generalized anxiety disorder (GAD): a meta-analysis of randomized controlled trials

The purpose of this meta-analysis was to provide updated pooled effect sizes of evidence-based psychotherapies and medications for generalized anxiety disorder (GAD) and to investigate potential moderators of outcomes. Seventy-nine randomized controlled trials (RCT) including 11,002 participants with a diagnosis of GAD were included in a meta-analysis that tested the efficacy of psychotherapies or medications for GAD. Psychotherapy showed a medium to large effect size (g = 0.76) and medication showed a small effect size (g = 0.38) on GAD outcomes. Psychotherapy also showed a medium effect on depression outcomes (g = 0.64) as did medications (g = 0.59). Younger age was associated with a larger effect size for psychotherapy (p < 0.05). There was evidence of publication bias in psychotherapy studies. This analysis found a medium to large effect for empirically supported psychotherapy interventions on GAD outcomes and a small effect for medications on GAD outcomes. Both groups showed a medium effect on depression outcomes. Because medication studies had more placebo control conditions than inactive conditions compared to psychotherapy studies, effect sizes between the domains should not be compared directly. Patient age should be further investigated as a potential moderator in psychotherapy outcomes in GAD