Journal
JAMA PSYCHIATRY
Volume 74, Issue 5, Pages 501-510Publisher
AMER MEDICAL ASSOC
DOI: 10.1001/jamapsychiatry.2016.3955
Keywords
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Categories
Funding
- Australian Rotary Health Research Fund
- Brain and Behavior Research Foundation Independent Investigator Award
- Brain and Behavior Research Foundation
- Robidoux Foundation Young Investigator Award
- DeWitt-Wallace Fund, New York Community Trust
- German Federal Ministry of Education and Research
- Hartford Hospital
- International OCD Foundation
- Massachusetts General Hospital
- National Health and Medical Research Council
- National Institutes of Health
- National Institute for Health Research (NIHR) Specialist Biomedical Research Centre for Mental Health
- National Institute of Mental Health
- Stichting Achmea Slachtoffer en Samenleving and Vereniging tot Christelijke Verzorging van Geestes- en Zenuwzieken
- Swedish Research Council
- Stockholm County Council
- National Institute on Drug Abuse
- Alicia Koplowitz Foundation
- National Center for Complementary and Integrative Health [R01AT007257]
- McDonnell Foundation 21st Century Science Initiative in Understanding Human Cognition - Special Initiative
- Department of the Army
- National Institute on Alcohol Abuse and Alcoholism [R01AA015069]
- Takeda
- Lundbeck
- Janssen
- National Institutes of Health [5T32DA007261-17]
- Rotary Mental Health Research Fund
- Edgemont
- McDonnell Center for Systems Neuroscience
- National Alliance for Research on Schizophrenia and Depression Independent Investigator Award
- Agency for Healthcare Research and Quality
- All Children's Hospital Research Foundation
- German Research Foundation
- European Commission
- Rotary Mental Health Research Fund Australia
- Swedish Research Council [K2013-61P-22168]
- National Institutes of Health K23 grant
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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 pre-specified 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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