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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.

Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden2Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden. Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. Institute of Psychiatry, Psychology, and Neuroscience, Department of Psychology, King's College London, London, United Kingdom. Department of Psychology, Southern Methodist University, Dallas, Texas. Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. Center for Anxiety Disorders Overwaal, Institution for Integrated Mental Health Care Pro Persona, Nijmegen, the Netherlands7Behavioral Science Institute, NijCare, Radboud University Nijmegen, Nijmegen, the Netherlands. Department of Psychiatry, Weill Cornell Medical College, New York, New York. Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia. School of Applied Psychology, Griffith University, Brisbane, Queensland, Australia11Menzies Health Institute of Queensland, Brisbane, Queensland, Australia. Department of Psychiatry, Massachusetts General Hospital, Boston13Harvard Medical School, Boston, Massachusetts. Brain and Mind Research Institute, Central Clinical School, University of Sydney, Sydney, New South Wales, Australia. Department of Psychological and Brain Sciences, Boston University, Boston, Massachusetts. Department of Psychiatry, University of Minnesota, Minneapolis. Department of Psychiatry, Washington University School of Medicine, St Louis, Missouri. University of Louisville, Louisville, Kentucky. Menzies Health Institute of Queensland, Brisbane, Queensland, Australia19School of Medicine, Griffith University, Brisbane, Queensland, Australia. Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité - University Medicine Berlin, Berlin, Germany. Department of Psychiatry, Rush University Medical Center, Chicago, Illinois. Harvard Medical School, Boston, Massachusetts22McLean Hospital, Belmont, Massachusetts. Department of Psychological and Brain Sciences, Washington University School of Medicine, St Louis, Missouri. Department of Psychiatry and Behavioral Sciences, Tulane University School of Medicine, New Orleans, Louisiana. School of Medicine, Griffith University, Brisbane, Queensland, Australia. Institute for Mental Health Research, Department of Psychology, The University of Texas, Austin. Department of Pediatrics, University of South Florida, Tampa27Rogers Behavioral Health, Tampa, Florida. New Mexico Veterans Affairs Health Care System, Albuquerque, New Mexico. The Institute of Living, Hartford, Connecticut30Yale University School of Medicine, New Haven, Massachusetts. Department of Human Development and Family Studies, Iowa State University, Ames. Department of Psychiatry, Weill Cornell Medical College, New York, New York32Cuny School of Public Health, City University of New York Graduate School of Public Health and Health Policy, New York. Department of Psychology, Georgia State University, Atlanta. Department of Psychiatry, University of Florida, Gainesville. Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York. Department of Psychiatry, Boston University School of Medicine, Boston, Massachusetts. Great Ormond Street Hospital for Children, University College London, London, United Kingdom. Department of Pediatrics, University of South Florida, Tampa. Minneapolis Veterans Affairs Health Care System, Minneapolis, Minnesota.

JAMA psychiatry. 2017;(5):501-510
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Abstract

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.

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Publication Type : Meta-Analysis ; Review

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