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Pilot-controlled trial of D-cycloserine for the treatment of post-traumatic stress disorder
Open accessAbstract
Dysfunction of glutamatergic neurotransmission may be relevant to the pathogenesis of post-traumatic stress disorder (PTSD). Preclinical and clinical evidence suggests that PTSD symptoms could be alleviated following enhancement of neurotransmission mediated at the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors. Eleven patients with chronic PTSD participated in a double-blind, placebo-controlled, cross-over trial with 50 mg/d D-cycloserine which acts as a partial agonist at the glycine regulatory site on the NMDA receptor. D-cycloserine treatment resulted in significant improvements in numbing, avoidance, and anxiety symptoms; however, similar effects were also observed during placebo treatment. In addition, D-cycloserine treatment resulted in a significant (p=0.03), reduction in the perseverative error scores as measured by the Wisconsin Card Sorting Test. This pilot study is the first to assess the efficacy of a NMDA receptor modulator for PTSD treatment and its results warrant further, larger-scale investigation.
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“This, considered collectively with findings from animal studies, leads to the postulation that DCS administration without extinction training cannot facilitate fear extinction.”
From Effects of Single Prolonged Stress and D-Cycloserine on Contextual Fear Extinction and Hippocampal NMDA Receptor Expression in a Rat Model of PTSD (2008) · cites this paper as Heresco-Levy et al, 2002
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“On the other hand, studies reported by Heresco-Levy et al (2002) did not demonstrate sufficient efficacy for DCS in the treatment of PTSD (Heresco-Levy et al, 2002).”
From Effects of Single Prolonged Stress and D-Cycloserine on Contextual Fear Extinction and Hippocampal NMDA Receptor Expression in a Rat Model of PTSD (2008) · cites this paper as Heresco-Levy et al (2002)
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Research works printed but not linked: 18
- Bouton ME, Bulles RC (1985). Contexts, event memories and extinction. In: Balsam PDD, Tomick A (Eds.), Context and Learning (pp. 133-166). Hillside NJ: Lawrence Erlbaum Associates.
- Davidson JRT (1997). Biological therapies for posttraumatic stress disorder: an overview. Journal of Clinical Psychiatry 58 (Suppl. 9), 29-32.
- Davidson JRT (2000). Pharmacotherapy of posttraumatic stress disorder : treatment option, long-term follow-up and predictors of outcome. Journal of Clinical Psychiatry 61 (Suppl. 5), 52-56.
- Friedman MJ (1988). Current and future drug treatment for posttraumatic stress disorder patients. Psychiatric Annals 28, 461-468.
- Friedman MJ (2000). What might the psychobiology of posttraumatic stress disorder teach us about future approaches to pharmacotherapy. Journal of Clinical Psychiatry 61 (Suppl. 7), 44-51.
- Glue P, Nutt DY, Coupland NJ (1993). Stress and psychiatric disorder : reconciling social and biological approaches. In : Stanford SC, Salmon P (Eds.), Stress: An Integrated Approach (pp. 53-73). London: Academic Press.
- Goff DC, Tsai G, Manoach DS, Coyle JT (1995). Dose-finding trial of D-cycloserine added to neuroleptics for negative symptoms in schizophrenia. American Journal of Psychiatry 152, 1213-1215.
- Hamilton M (1959). The assessment of anxiety states by rating. British Journal of Medical Psychology 175, 17-22.
- Hamilton M (1960). A rating scale for depression. Journal of Neurological and Neurosurgical Psychiatry 23, 56-62.
- Heresco-Levy U (2000). N-methyl-D-aspartate (NMDA) receptor-based treatment approaches in schizophrenia : the first decade. International Journal of Neuropsychopharmacology 3, 243-258.
- Heresco-Levy U, Ermilov M, Shimoni J, Shapira B, Silipo G, Javitt DC (2002). Placebo-controlled trial of D-cycloserine added to conventional neuroleptics, olanzapine or risperidone in schizophrenia. American Journal of Psychiatry 159, 480-482.
- Jones RW, Wesnes KA, Kirby J (1991). Effects of NMDA modulation in scopolamine dementia. Annals of the New York Academy of Science 640, 241-244.
- Kessler RB (2000). Posttraumatic Stress Disorder: the burden to the individual and to society. Journal of Clinical Psychiatry 61 (Suppl. 5), 4-12.
- Marshall RD, Davidson JRT, Yehuda R (1998). Pharmacotherapy in the treatment of posttraumatic stress disorder and other trauma-related syndromes. In : Yehuda R (Ed.), Psychological Trauma, Review of Psychiatry, vol. 17 (pp. 133-177). Washington, DC : American Psychiatric Press.
- McAllister WR, McAllister DE (1998). Reconditioning of extinguished fear after a one-year delay. Bulletin of the Psychonomic Society 26, 463-466.
- Nutt DJ (2000). The psychobiology of posttraumatic stress disorder. Journal of Clinical Psychiatry 61 (Suppl. 5), 24-32.
- Vakil E, Blachstein H (1993). Rey Auditory-Verbal Learning Test: structure analysis. Journal of Clinical Psychology 49, 883-890.
- Vreven DL, Gudanowski DM, King LA, King DW (1995). The civilian version of the Mississippi PTSD scale: a psychometric evaluation. Journal of Trauma and Stress 8, 91-109.
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“In chronic post-traumatic stress disorder (PTSD), this dosing improves avoidance, numbing, and anxiety symptoms,while also enhancing performance on the Wisconsin Card Sorting Test [59].”
Metadata
- Authors
- Heresco-Levy, U., Kremer, I., Javitt, D. C., Goichman, R., Reshef, A., Blanaru, M., & Cohen, T.
- Affiliations
- Technion – Israel Institute of Technology (IL)
- Nathan Kline Institute for Psychiatric Research (US)
- Venue
- The International Journal of Neuropsychopharmacology
- Publisher
- Oxford University Press (OUP)
- Published
- 2002-12
- Volume
- 5
- Issue
- 4
- Pages
- 301-307
- ISSN
- 1461-1457 (ISSN-L)
- 1469-5111
- OpenAlex
- W4213356598
- Cited by
- 134
- References
- 0
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 2 · 2023: 1 · 2022: 3 · 2021: 3 · 2020: 2 · 2019: 1 · 2018: 3 · 2017: 8 · 2016: 10 · 2015: 5 · 2014: 11 · 2013: 4 · 2012: 10
- FWCI
- 3.98
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The International Journal of Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
- Social Sciences › Psychology › Clinical Psychology › Psychoanalysis and Psychopathology Research
- Social Sciences › Psychology › Clinical Psychology › Migration, Health and Trauma
- Keywords
- D-cycloserine, post-traumatic stress disorder, NMDA receptor modulation, glutamatergic neurotransmission, chronic PTSD, Wisconsin Card Sorting Test, avoidance symptoms, anxiety symptoms, numbing symptoms
- MeSH terms
- Adult, Antibiotics, Antitubercular, Chronic Disease, Cognition, Cycloserine, Double-Blind Method, Female, Humans, Male, Middle Aged, Pilot Projects, Psychiatric Status Rating Scales, Stress Disorders, Post-Traumatic, Receptors, Glycine, Cross-Over Studies
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