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Does D-cycloserine enhance exposure therapy for anxiety disorders in humans? A meta-analysis.

ABSTRACT: The treatment of anxiety is on the edge of a new era of combinations of pharmacologic and psychosocial interventions. A new wave of translational research has focused on the use of pharmacological agents as psychotherapy adjuvants using neurobiological insights into the mechanism of the action of certain psychological treatments such as exposure therapy. Recently, d-cycloserine (DCS) an antibiotic used to treat tuberculosis has been applied to enhance exposure-based treatment for anxiety and has proved to be a promising, but as yet unproven intervention. The present study aimed to evaluate the efficacy of DCS in the enhancement of exposure therapy in anxiety disorders. A systematic review/meta-analysis was conducted. Electronic searches were conducted in the databases ISI-Web of Science, Pubmed and PsycINFO. We included only randomized, double-blind, placebo-controlled trials with humans, focusing on the role of DCS in enhancing the action of exposure therapy for anxiety disorders. We identified 328 references, 13 studies were included in our final sample: 4 on obsessive-compulsive disorder, 2 on panic disorder, 2 on social anxiety disorder, 2 on posttraumatic stress disorder, one on acrophobia, and 2 on snake phobia. The results of the present meta-analysis show that DCS enhances exposure therapy in the treatment of anxiety disorders (Cohen d =? -0.34; CI: -0.54 to -0.14), facilitating the specific process of extinction of fear. DCS seems to be effective when administered at a time close to the exposure therapy, at low doses and a limited number of times. DCS emerges as a potential new therapeutic approach for patients with refractory anxiety disorders that are unresponsive to the conventional treatments available. When administered correctly, DCS is a promising strategy for augmentation of CBT and could reduce health care costs, drop-out rates and bring faster relief to patients.

SUBMITTER: Rodrigues H

PROVIDER: S-EPMC4081005 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Project description:In virtual reality exposure therapy (VRET) for anxiety disorders, sense of presence in the virtual environment is considered the principal mechanism that enables anxiety to be felt. Existing studies on the relation between sense of presence and level of anxiety, however, have yielded mixed results on the correlation between the two. In this meta-analysis, we reviewed publications on VRET for anxiety that included self-reported presence and anxiety. The comprehensive search of the literature identified 33 publications with a total of 1196 participants. The correlation between self-reported sense of presence and anxiety was extracted and meta-analyzed. Potential moderators such as technology characteristics, sample characteristics including age, gender and clinical status, disorder characteristics and study design characteristics such as measurements were also examined. The random effects analysis showed a medium effect size for the correlation between sense of presence and anxiety (r = .28; 95% CI: 0.18-0.38). Moderation analyses revealed that the effect size of the correlation differed across different anxiety disorders, with a large effect size for fear of animals (r = .50; 95% CI: 0.30-0.66) and a no to small effect size for social anxiety disorder (r = .001; 95% CI: -0.19-0.19). Further, the correlation between anxiety and presence was stronger in studies with participants who met criteria for an anxiety disorder than in studies with a non-clinical population. Trackers with six degrees of freedom and displays with a larger field of view resulted in higher effect sizes, compared to trackers with three degrees of freedom and displays with a smaller field of view. In addition, no difference in effect size was found for the type of presence measurement and the type of anxiety measurement. This meta-analysis confirms the positive relation between sense of presence and anxiety and demonstrates that this relation can be affected by various moderating factors.

Project description:ObjectiveThe evidence for the efficacy of D-cycloserine (DCS) for augmenting cognitive behavioral therapy (CBT) for anxiety disorders has been mixed. Guided by preclinical research and initial findings from a small-scale study involving humans, we tested the hypothesis that DCS enhancement of exposure therapy would be specific to successful exposure sessions.MethodMedication-free adults with generalized social anxiety disorder (N = 145) received 50 mg of DCS or placebo 1 h before each of 5 exposure sessions that were part of a standardized 12-session group CBT protocol. Participants provided fear ratings at the beginning and just before the end of exposure exercises. Independent raters, blind to group assignment, administered the clinical global impression improvement and severity scales at each session and at posttreatment.ResultsMixed-effects analyses revealed that, among patients who reported low fear at the end of an exposure session, those who had received DCS evidenced significantly greater clinical improvement at the next session, relative to those who had received placebo. In contrast, when exposure end fear was high, patients receiving DCS exhibited less clinical improvement at the following session than patients receiving placebo. Similarly, patients who had received DCS evidenced lower clinical severity at posttreatment, relative to patients who had received placebo, only when their average end fear for medication-augmented sessions had been in the low to moderate range. Finally, these moderating effects of exposure success as indexed by end fear were not better accounted for by within-session extinction.ConclusionsThe efficacy of DCS for augmenting exposure-based CBT depends on the success of exposure sessions. These findings may help guide the development of an algorithm for the effective use of DCS for augmenting exposure-based CBT.Trial registryhttp://www.ClinicalTrials.gov, ID# NCT00633984, http://www.clinicaltrials.gov/ct2/show/NCT00633984.

Project description:Importance:Findings suggest that the efficacy of D-cycloserine (DCS) for enhancing exposure therapy may be strongest when administered after sessions marked by low fear at the conclusion of exposure practice. These findings have prompted investigation of DCS dosing tailored to results of exposure sessions. Objective:To compare tailored postsession DCS administration with presession DCS administration, postsession DCS administration, and placebo augmentation of exposure therapy for social anxiety disorder. Design, Setting, and Participants:This double-blind randomized clinical trial involved adults with social anxiety disorder enrolled at 3 US university centers. Symptom severity was assessed at baseline, weekly during treatment, and at 1-week and 3-month follow-up. Data analysis was performed from September 2019 to March 2020. Interventions:Participants completed a 5-session treatment and received pills commensurate with their condition assignment at sessions 2 through 5, which emphasized exposure practice. Main Outcomes and Measures:Symptom severity was evaluated by the Liebowitz Social Anxiety Scale and Social Phobic Disorders-Severity Form as administered by independent evaluators. Results:A total of 152 participants were enrolled (mean [SD] age, 29.24 [10.16] years; 84 men [55.26%]). Compared with placebo, presession and postsession conditions showed greater symptom improvement (b = -0.25; 95% CI, -0.37 to -0.13; P < .001; d = 1.07; and b = -0.20; 95% CI, -0.32 to -0.07; P = .002; d = 0.85) and lower symptom severity (b = -0.51; 95% CI, -0.81 to -0.21; P < .001; d = 0.76; and b = -0.49; 95% CI, -0.80 to -0.18; P = .002; d = 0.72) at 3-month follow-up. No differences were found between presession and postsession conditions. The tailored condition showed no advantage over placebo. Compared with the tailored condition, presession and postsession conditions evidenced greater decreases (b = -0.22; 95% CI, -0.34 to -0.10; P < .001; d = 0.94; and b = -0.17, 95% CI, -0.29 to -0.04; P = .008; d = 0.72) and lower symptom severity (b = -0.44, 95% CI, -0.73 to -0.14; P = .004; d = 0.64; and b = -0.41, 95% CI, -0.72 to -0.11; P = .008; d = 0.61) at 3-month follow-up. Conclusions and Relevance:Administration of DCS enhanced exposure therapy for social anxiety disorder when given before or after the exposure session. However, the study failed to achieve the aim to develop a tailored clinical application. Trial Registration:ClinicalTrials.gov Identifier: NCT02066792.

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Does D-cycloserine enhance exposure therapy for anxiety disorders in humans? A meta-analysis.

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