Archival Report| Volume 71, ISSUE 11, P962-968, June 01, 2012

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A Randomized Placebo-Controlled Trial of d-Cycloserine to Enhance Exposure Therapy for Posttraumatic Stress Disorder

  • Rianne A. de Kleine
    Address correspondence to Rianne de Kleine, M.Sc., Center for Anxiety Disorders Overwaal, Tarweweg 2, 6543 AM Nijmegen, The Netherlands
    Radboud University Nijmegen, Behavioural Science Institute, NijCare, The Netherlands

    Center for Anxiety Disorders Overwaal, Nijmegen, The Netherlands
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  • Gert-Jan Hendriks
    Radboud University Nijmegen, Behavioural Science Institute, NijCare, The Netherlands

    Center for Anxiety Disorders Overwaal, Nijmegen, The Netherlands

    Outpatient Mental Health Clinic Hendriks and Roosenboom, Arnhem, The Netherlands

    Department of Psychiatry, Radboud University Medical Centre, Nijmegen, The Netherlands
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  • Wendy J.C. Kusters
    Radboud University Nijmegen, Behavioural Science Institute, NijCare, The Netherlands

    Outpatient Mental Health Clinic Hendriks and Roosenboom, Arnhem, The Netherlands
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  • Theo G. Broekman
    Bureau Bêta, Nijmegen, The Netherlands
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  • Agnes van Minnen
    Radboud University Nijmegen, Behavioural Science Institute, NijCare, The Netherlands

    Center for Anxiety Disorders Overwaal, Nijmegen, The Netherlands
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      Posttraumatic stress disorder (PTSD) is a complex and debilitating anxiety disorder, and, although prolonged exposure therapy has been proven effective, many patients remain symptomatic after treatment. In other anxiety disorders, the supplementary use of d-cycloserine (DCS), a partial agonist at the glutamatergic N-methyl-D-aspartate receptor, showed promise in enhancing treatment effects. We examined whether augmentation of prolonged exposure therapy for PTSD with DCS enhances treatment efficacy.


      In a randomized, double-blind, placebo-controlled trial we administered 50 mg DCS or placebo 1 hour before each exposure session to 67 mixed trauma patients, recruited from regular referrals, with a primary PTSD diagnosis satisfying DSM-IV criteria.


      Although DCS did not enhance overall treatment effects, the participants having received DCS did show a stronger treatment response. Exploratory session-by-session analyses revealed that DCS yielded higher symptom reduction in those participants that had more severe pretreatment PTSD and needed longer treatment.


      The present study found preliminary support for the augmentation of exposure therapy with DCS, specifically for patients with more severe PTSD needing longer treatment.

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