d-Cycloserine Augmentation of Behavioral Therapy for the Treatment of Anxiety Disorders: A Meta-Analysis
Open accessAbstract
OBJECTIVE: To determine the efficacy of D-cycloserine augmentation of behavioral therapy for the treatment of anxiety disorders. DATA SOURCES AND STUDY SELECTION: Using the search terms D-cycloserine AND anxiety disorders (MeSH), PubMed (1965-June 2011), PsycINFO, and Scopus were searched for randomized, double-blind, placebo-controlled trials of D-cycloserine augmentation of behavioral therapy for the treatment of anxiety disorders. Anxiety disorders were defined as any disorder categorized as such in DSM-IV-TR. DATA EXTRACTION: A random-effects model was used to calculate the standardized mean difference of change in anxiety rating scale scores with D-cycloserine augmentation compared to placebo, which was the primary outcome measure. Subgroup analysis and meta-regression were used to examine the effects of D-cycloserine dosage and timing (relative to exposure therapy), diagnostic indication, number of therapy sessions, and trial methodological quality on D-cycloserine efficacy. RESULTS: Meta-analysis of 9 trials involving 273 subjects demonstrated a significant benefit from D-cycloserine augmentation (standardized mean difference = 0.46 [95% CI, 0.15 to 0.77], z = 2.89, P = .004). There was no evidence of publication bias, but a moderate, nonsignificant degree of heterogeneity between trials (I2 = 36%, Q = 12.6, df = 8, P = .12) was found. Secondary analyses yielded no significant findings. CONCLUSIONS: D-Cycloserine appears to be an effective augmentation agent that enhances the effects of behavioral therapy in the treatment of anxiety disorders. In contrast to a previous meta-analysis that examined D-cycloserine's effects in both animals and humans, we found no evidence of an effect of dose number, dose timing, or dosage of D-cycloserine on reported efficacy in the ranges studied.
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D-cycloserine is an NMDA receptor partial agonist that promotes NMDA-dependent memory consolidation of therapeutic extinction memory.
“D-cycloserine, an NMDA receptor partial agonist, that promotes NMDA-dependent memory consolidation of therapeutic extinction memory [238–240].”
From Sleep and REM sleep disturbance in the pathophysiology of PTSD: the role of extinction memory (2015) · cites this paper as [239]
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- Authors
- Bontempo, A., Panza, K. E., & Bloch, M. H.
- Affiliations
- Yale University (US)
- Venue
- The Journal of Clinical Psychiatry
- Publisher
- Physicians Postgraduate Press, Inc
- Published
- 2012-04-15
- Volume
- 73
- Issue
- 04
- Pages
- 533-537
- ISSN
- 0160-6689 (ISSN-L)
- PMC
- PMC3625928
- OpenAlex
- W2038412514
- Cited by
- 69
- References
- 18
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 1 · 2022: 1 · 2020: 1 · 2019: 2 · 2018: 8 · 2017: 6 · 2016: 13 · 2015: 11 · 2014: 10 · 2013: 8 · 2012: 6
- FWCI
- 14.99
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- The Journal of Clinical Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Eli Lilly and Company
- American Academy of Child and Adolescent Psychiatry
- National Institutes of Health
- National Institute of Mental Health (K23MH091240, R25MH077823)
- National Center for Research Resources (UL1RR024139)
- Topics
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Social Sciences › Psychology › Clinical Psychology › Psychotherapy Techniques and Applications
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- D-cycloserine, augmentation therapy, behavior therapy, anxiety disorders, exposure therapy, glutamate receptor agonists, treatment efficacy, timing of drug administration, dose number
- MeSH terms
- Anxiety Disorders, Behavior Therapy, Combined Modality Therapy, Cycloserine, Humans, Anti-Anxiety Agents, Treatment Outcome
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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