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D-cycloserine enhancement of fear extinction is specific to successful exposure sessions: evidence from the treatment of height phobia.

ABSTRACT: Whereas some studies have shown clear evidence for an augmentation effect of D-cycloserine (DCS) on exposure therapy for anxiety disorders, other studies have shown weak effects or no effect at all. Some preclinical data suggest that the DCS augmentation effect is moderated by the success of extinction learning. Therefore, we conducted a reanalysis of existing data to examine whether the effects of DCS on clinical outcome would vary as a function of response to the exposure session (i.e., exposure success).In a clinical trial, patients with height phobia received two sessions involving 30 minutes of virtual reality exposure therapy and were randomly assigned to a pill placebo (n = 14) or 50 mg of DCS (n = 15) immediately after each session.Mixed-effects regression analysis showed that the effects of DCS administration on clinical improvement was moderated by the level of fear experienced just before concluding exposure sessions. Patients receiving DCS exhibited significantly greater improvement in symptoms relative to patients who received placebo when fear was low at the end of the exposure. In contrast, when end fear was still elevated, patients receiving DCS improved less compared with those receiving placebo.D-cycloserine appears to enhance the benefits of exposure treatment when applied after a successful session, but it seems to have detrimental effects when administered after inadequate/unsuccessful exposure sessions.

SUBMITTER: Smits JA

PROVIDER: S-EPMC3636175 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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D-cycloserine enhancement of fear extinction is specific to successful exposure sessions: evidence from the treatment of height phobia.

Smits Jasper A J JA Rosenfield David D Otto Michael W MW Powers Mark B MB Hofmann Stefan G SG Telch Michael J MJ Pollack Mark H MH Tart Candyce D CD

Biological psychiatry 20130116 11

<h4>Background</h4>Whereas some studies have shown clear evidence for an augmentation effect of D-cycloserine (DCS) on exposure therapy for anxiety disorders, other studies have shown weak effects or no effect at all. Some preclinical data suggest that the DCS augmentation effect is moderated by the success of extinction learning. Therefore, we conducted a reanalysis of existing data to examine whether the effects of DCS on clinical outcome would vary as a function of response to the exposure se ...[more]

PMID: 23332511

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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.

Dataset Information

D-cycloserine enhancement of fear extinction is specific to successful exposure sessions: evidence from the treatment of height phobia.

Publications

D-cycloserine enhancement of fear extinction is specific to successful exposure sessions: evidence from the treatment of height phobia.

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