Cited by 510Memory and Neural MechanismsPosttraumatic Stress Disorder ResearchAnxiety, Depression, Psychometrics, Treatment, Cognitive Processes

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A Meta-Analysis of D-Cycloserine and the Facilitation of Fear Extinction and Exposure Therapy

Norberg, Melissa M., Krystal, John H., Tolin, David F.·2008·Biological Psychiatry

DOI 10.1016/j.biopsych.2008.01.012

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Abstract

Background Translational research suggests that D-cycloserine (DCS), a partial N-methyl-D-aspartate (NMDA) receptor agonist, might facilitate fear extinction and exposure therapy by either enhancing NMDA receptor function during extinction or by reducing NMDA receptor function during fear memory consolidation. This article provides a quantitative review of DCS-augmented fear extinction and exposure therapy literature.Methods English-language journal articles that examined DCS augmented with fear extinction or exposure therapy were identified through public databases from June 1998 through September 2007, through references of originally identified articles and contact with DCS investigators. Data were extracted for study author, title, and year; trial design; type of subject (animal vs. human; clinical vs. nonclinical); sample size, DCS dose, and timing in relation to extinction/exposure procedures; dependent variable; group means and SDs at post-extinction/exposure; and follow-up outcome.Results D-cycloserine enhances fear extinction/exposure therapy in both animals and anxiety-disordered humans. Gains generally were maintained at follow-up, although some lessening of efficacy was noted. D-cycloserine was more effective when administered a limited number of times and when given immediately before or after extinction training/exposure therapy.Conclusions This meta-analysis suggests that DCS is a useful target for translational research on augmenting exposure-based treatment via compounds that impact neuroplasticity. D-cycloserine 's major contribution to exposure-based therapy might be to increase its speed or efficiency, because the effects of DCS seem to decrease over repeated sessions. This information might guide translational researchers in discovering more selective and/or effective agents that effectively enhance (or reduce) NMDA receptor function.

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Authors: Norberg, M. M., Krystal, J. H., & Tolin, D. F.
Affiliations: Yale University (US)
Corresponding author: Tolin, David F.
ORCID: Norberg, Melissa M.
Krystal, John H.
Tolin, David F.
Venue: Biological Psychiatry
Publisher: Elsevier BV
Published: 2008-06
Volume: 63
Issue: 12
Pages: 1118-1126
ISSN: 0006-3223 (ISSN-L)
DOI: 10.1016/j.biopsych.2008.01.012
OpenAlex: W2159630298
Cited by: 510
References: 121
Citations by year: 2026: 10 · 2025: 9 · 2024: 8 · 2023: 8 · 2022: 15 · 2021: 13 · 2020: 12 · 2019: 16 · 2018: 28 · 2017: 28 · 2016: 23 · 2015: 50 · 2014: 37 · 2013: 53 · 2012: 51
FWCI: 3.80
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Biological Psychiatry (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
Keywords: D-cycloserine, fear extinction, exposure therapy, NMDA receptor agonist, anxiety disorders, fear memory consolidation, neuroplasticity, augmentation therapy, translational research
MeSH terms: Animals, Anxiety Disorders, Combined Modality Therapy, Cycloserine, Desensitization, Psychologic, Extinction, Psychological, Fear, Humans, Implosive Therapy, Neuronal Plasticity, Receptors, N-Methyl-D-Aspartate, Treatment Outcome

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A Meta-Analysis of D-Cycloserine and the Facilitation of Fear Extinction and Exposure Therapy

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