SynthesisJournal of anxiety disorders2019
Changes in Dosing and Dose Timing of D-Cycloserine Explain Its Apparent Declining Efficacy for Augmenting Exposure Therapy for Anxiety-related Disorders: An Individual Participant-data Meta-analysis.
Open access · greenAbstract readMeta-Analysis
In one paragraph
Synthesis in Journal of anxiety disorders, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 2 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed, 2 pooled it
4.9field-weighted citation impact, top 4% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed, 2 syntheses or guidelines pooled it, 54 citations in OpenAlex.
- A systematic review of the pharmacological modulation of autobiographical memory specificity.Frontiers in psychology · 2022Pooled it
- Fear conditioning and extinction in obsessive-compulsive disorder: A systematic review.Neuroscience and biobehavioral reviews · 2021Pooled it
- Exposure therapy consortium: Outcomes of the proof-of-principle study.Journal of anxiety disorders · 2025Trial
- Randomized controlled experimental study of hydrocortisone and D-cycloserine effects on fear extinction in PTSD.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2022Trial
- Enhancing exposure therapy for posttraumatic stress disorder (PTSD): a randomized clinical trial of virtual reality and imaginal exposure with a cognitive enhancer.Translational psychiatry · 2022Trial
- Effect of D-Cycloserine on the Effect of Concentrated Exposure and Response Prevention in Difficult-to-Treat Obsessive-Compulsive Disorder: A Randomized Clinical Trial.JAMA network open · 2020Trial
- Dose Timing of D-Cycloserine to Augment Exposure Therapy for Social Anxiety Disorder: A Randomized Clinical Trial.JAMA network open · 2020Trial
- Enhancing the Efficacy of Exposure Therapy: Translation of Pharmacological Augmentation of Fear Extinction.Annual review of clinical psychology · 2026Review
- Adjunct psychomotor trauma exposure in the treatment of post-traumatic stress disorder: a case series.European journal of psychotraumatology · 2025Article
- Mechanisms of Change in Exposure Therapy for Anxiety and Related Disorders: A Research Agenda.Clinical psychological science : a journal of the Association for Psychological Science · 2025Article
- Using pre-treatment de novo threat conditioning outcomes to predict treatment response to DCS augmentation of exposure-based CBT.Journal of psychiatric research · 2023Article
- Alleviating anxiety and taming trauma: Novel pharmacotherapeutics for anxiety disorders and posttraumatic stress disorder.Neuropharmacology · 2023Review
- The effect of d-cycloserine on brain processing of breathlessness over pulmonary rehabilitation: an experimental medicine study.ERJ open research · 2023Article
- Enhancing Psychological Interventions for Post-Traumatic Stress Disorder (PTSD) Treatment with Memory Influencing Drugs.Current neuropharmacology · 2023Review
- Psychotherapies and digital interventions for OCD in adults: What do we know, what do we need still to explore?Comprehensive psychiatry · 2023Review
- Causally mapping human threat extinction relevant circuits with depolarizing brain stimulation methods.Neuroscience and biobehavioral reviews · 2023Review
- Understanding Human Fear Extinction: Insights from Psychophysiology.Current topics in behavioral neurosciences · 2023Article
- Enhancing Fear Extinction: Pharmacological Approaches.Current topics in behavioral neurosciences · 2023Article
- A Case for Translation From the Clinic to the Laboratory.Perspectives on psychological science : a journal of the Association for Psychological Science · 2022Article
- Cognitive-Behavioral Treatments for Anxiety and Stress-Related Disorders.Focus (American Psychiatric Publishing) · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
55 authors at 20 institutions in 5 countries.
David RosenfieldDepartment of Psychology, Southern Methodist University, Dallas, USA. Electronic address: drosenfi@smu.edu.
Jasper A J SmitsInstitute for Mental Health Research and Department of Psychology, The University of Texas, Austin, USA.
Stefan G HofmannDepartment of Psychological and Brain Sciences, Boston University, Boston, USA.
David Mataix-ColsCentre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden.
Lorena Fernández de la CruzCentre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden.
Erik AnderssonCentre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Christian RückCentre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden.
Benedetta MonzaniDepartment of Psychology, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK.
Ana Pérez-VigilCentre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Paolo FrumentoUnit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Michael DavisDepartment of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, USA.
Rianne A de KleineInstitute of Psychology, Leiden University, The Netherlands.
JoAnn DifedeDepartment of Psychiatry, Weill Cornell Medical College, NY, USA.
Boadie W DunlopDepartment of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, USA.
Lara J FarrellSchool of Applied Psychology, Griffith University, Brisbane, Australia; Menzies Health Institute of Queensland, Brisbane, Australia.
Daniel GellerDepartment of Psychiatry, Massachusetts General Hospital, Boston, USA; Harvard Medical School, Boston, USA.
Maryrose GerardiDepartment of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, USA.
Adam J GuastellaBrain and Mind Research Institute, Central Clinical School, University of Sydney, Sydney, Australia.
Gert-Jan HendriksBehavioral Science Institute, Radboud University Nijmegen, The Netherlands; Overwaal Center of Expertise for Anxiety Disorders OCD and PTSD, Institution for Integrated Mental Health Care Pro Persona, Nijmegen, the Netherlands.
Matt G KushnerDepartment of Psychiatry, University of Minnesota-Twin Cities, Minneapolis, USA.
Francis S LeeDepartment of Psychiatry, Weill Cornell Medical College, NY, USA.
Eric J LenzeDepartment of Psychiatry, Washington University School of Medicine, St Louis, USA.
Cheri A LevinsonDepartment of Psychiatry, Washington University School of Medicine, St Louis, USA.
Harry McConnellMenzies Health Institute of Queensland, Brisbane, Australia; School of Medicine, Griffith University, Brisbane, Australia.
Jens PlagDepartment of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité - University Medicine Berlin, Germany.
Mark H PollackDepartment of Psychiatry, Rush University Medical Center, Chicago, USA.
Kerry J ResslerHarvard Medical School, Boston, USA; McLean Hospital, Belmont, USA.
Thomas L RodebaughDepartment of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, USA.
Barbara O RothbaumDepartment of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, USA.
Eric A StorchMenninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, USA.
Andreas StröhleDepartment of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité - University Medicine Berlin, Germany.
Candyce D TartNew Mexico VA Health Care System, Albuquerque, USA.
David F TolinThe Institute of Living, Hartford, USA; Yale University School of Medicine, New Haven, USA.
Agnes van MinnenBehavioral Science Institute, Radboud University Nijmegen, The Netherlands.
Allison M WatersSchool of Applied Psychology, Griffith University, Brisbane, Australia.
Carl F WeemsDepartment of Human Development and Family Studies, Iowa State University, Ames, USA.
Sabine WilhelmDepartment of Psychiatry, Massachusetts General Hospital, Boston, USA; Harvard Medical School, Boston, USA.
Katarzyna WykaDepartment of Psychiatry, Weill Cornell Medical College, NY, USA; City University of New York Graduate School of Public Health and Health Policy, New York, USA.
Margaret AltemusYale University School of Medicine, New Haven, USA.
Page AndersonDepartment of Psychology, Georgia State University, Atlanta, USA.
Judith CukorDepartment of Psychiatry, Weill Cornell Medical College, NY, USA.
Claudia FinckDRK Kliniken Berlin Wiegmann Klinik, Berlin, Germany.
Gary R GeffkenGeffken Group, PLLC, Gainesville, FL, USA.
Fabian GolfelsWoltersdorf Hospital, Woltersdorf, Germany.
Wayne K GoodmanDepartment of Psychiatry, Baylor College of Medicine, USA.
Cassidy A GutnerDepartment of Psychiatry, Boston University School of Medicine, Boston, USA.
Isobel HeymanGreat Ormond Street Hospital for Children, London, UK; University College, London, UK.
Tanja JovanovicDepartment of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, USA.
Adam B LewinDepartment of Pediatrics, University of South Florida, Tampa, USA.
Joseph P McNamaraDepartment of Psychiatry, University of Florida, Gainesville, USA.
Tanya K MurphyDepartment of Pediatrics, University of South Florida, Tampa, USA.
Seth NorrholmDepartment of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, USA.
Paul ThurasDepartment of Psychiatry, University of Minnesota-Twin Cities, Minneapolis, USA.
Cynthia TurnerPrimary Care Clinical Unit, Faculty of Medicine, The University of Queensland, Brisbane, Australia.
Michael W OttoDepartment of Psychological and Brain Sciences, Boston University, Boston, USA.
Emory University · USKarolinska Institutet · SECornell University · USBaylor College of Medicine · USGriffith University · AUUniversity of South Florida · USWashington University in St. Louis · USBoston University · USGeorgia State University · USIowa State University · USKing's College London · GBLeiden University · NLMassachusetts General Hospital · USNew Mexico VA Health Care System · USPro Persona · NLRadboud University Nijmegen · NLRush University Medical Center · USSouthern Methodist University · USTexas Research Institute · USTwin Cities Orthopedics · US
Funding
BIOMEDICAL RESEARCH TRAINING IN DRUG ABUSET32DA007261 · NIDA · WASHINGTON UNIVERSITY · PI ARPANA AGRAWAL, Jose A Moron-Concepcion · 1991 to 2026
$8.8MDismantling the Components and Dosing of CBT for Co-Occurring DisordersR01AA015069 · NIAAA · UNIVERSITY OF MINNESOTA TWIN CITIES · PI KUSHNER, MATT G · 2005 to 2018
$3.8MToward Outcome Measurement of Anxiety in Youth with Autism Spectrum DisordersR01MH099021 · NIMH · YALE UNIVERSITY · PI SCAHILL, LAWRENCE D. · 2012 to 2015
$2.7MCognitive Enhancer May Facilitate Behavioral ExposureR01MH070880 · NIMH · EMORY UNIVERSITY · PI ROTHBAUM, BARBARA O · 2005 to 2010
$2.2M1/2-Yoga For Generalized Anxiety DisorderR01AT007257 · NCCIH · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · PI HOFMANN, STEFAN G. · 2013 to 2017
$2.0MD-Cycloserine Enhancement of Exposure in Social PhobiaR01MH078308 · NIMH · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · PI HOFMANN, STEFAN G. · 2007 to 2010
$1.3M1/3-Exposure D-Cycloserine Enhancement and Genetic Modulators in Panic DisorderR01MH081116 · NIMH · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · PI OTTO, MICHAEL W. · 2008 to 2012
$1.2MEffect of D-cycloserine on treatment of PTSD in youthRC1MH088969 · NIMH · TULANE UNIVERSITY OF LOUISIANA · PI SCHEERINGA, MICHAEL S · 2009 to 2010
$927kEffectiveness of a unified transdiagnostic treatment in routine clinical careK23MH103396 · NIMH · BOSTON UNIVERSITY MEDICAL CAMPUS · PI GUTNER, CASSIDY AUBIN · 2015 to 2019
$898kNeural Dimensions of Attention Bias Modification for Transdiagnostic AnxietyK23MH100259 · NIMH · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI PRICE, REBECCA · 2013 to 2017
$788k2/3-Dose Timing of D-cycloserine to Augment CBT for Social Anxiety DisorderR34MH099311 · NIMH · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · PI HOFMANN, STEFAN G. · 2014 to 2016
$737kExposure Therapy for Fear of Falling in Older AdultsR34MH086668 · NIMH · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI WETHERELL, JULIE L · 2010 to 2012
$691kNCCIH NIH HHS R01 AT007257NIAAA NIH HHS R01 AA015069NIDA NIH HHS R21 DA030808NIDA NIH HHS T32 DA007261NIMH NIH HHS K23 MH100259NIMH NIH HHS K23 MH103396NIMH NIH HHS R01 MH070880NIMH NIH HHS R01 MH078308NIMH NIH HHS R01 MH081116NIMH NIH HHS R01 MH099021NIMH NIH HHS R21 MH090308NIMH NIH HHS R21 MH101567NIMH NIH HHS R21 MH102646NIMH NIH HHS R34 MH086668NIMH NIH HHS R34 MH099311NIMH NIH HHS RC1 MH088969
Abstract
The apparent efficacy of d-cycloserine (DCS) for enhancing exposure treatment for anxiety disorders appears to have declined over the past 14 years. We examined whether variations in how DCS has been administered can account for this "declining effect". We also investigated the association between DCS administration characteristics and treatment outcome to find optimal dosing parameters. We conducted a secondary analysis of individual participant data obtained from 1047 participants in 21 studies testing the efficacy of DCS-augmented exposure treatments. Different outcome measures in different studies were harmonized to a 0-100 scale. Intent-to-treat analyses showed that, in participants randomized to DCS augmentation (n = 523), fewer DCS doses, later timing of DCS dose, and lower baseline severity appear to account for this decline effect. More DCS doses were related to better outcomes, but this advantage leveled-off at nine doses. Administering DCS more than 60 minutes before exposures was also related to better outcomes. These predictors were not significant in the placebo arm (n = 521). Results suggested that optimal DCS administration could increase pre-to-follow-up DCS effect size by 50%. In conclusion, the apparent declining effectiveness of DCS over time may be accounted for by how it has been administered. Optimal DCS administration may substantially improve outcomes. Registration: The analysis plan for this manuscript was registered on Open Science Framework (https://osf.io/c39p8/).
Indexed as
AdolescentAdultAgedAnxietyAnxiety DisordersChildCombined Modality TherapyCycloserineFemaleHumansImplosive TherapyMaleMiddle AgedTreatment OutcomeYoung AdultCycloserineaugmentationd-cycloserinedecline effectdosingexposure
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