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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DCS administration without extinction training cannot facilitate fear extinction.
“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
Studies reported by Heresco-Levy et al (2002) did not demonstrate sufficient efficacy for DCS in the treatment of PTSD.
“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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Yehuda, R., & LeDoux, J. E. (2007) · Neuron · doi:10.1016/j.neuron.2007.09.006 · Cited by 795 · see citing works
Glutamate as a therapeutic target in psychiatric disorders
Javitt, D. C. (2004) · Molecular Psychiatry · doi:10.1038/sj.mp.4001551 · Cited by 524 · see citing works
“001 11.7 0.001 13 0.001 186 Tsai et al (1999) DSER Clozapine 20 2.5 NS 0.8 NS 3.6 NS 98 Goff et al (1999) DCS Conventional 47 23 o.02c — — — NS 187 Heresco-Levy et al (2002) DCS Mixed 21a 14 o.05 — — — NS 188 Goff et al (1999) DCS Clozapine 17a þ 13d o.005 — — — NS 189 —¼not determined; NS¼not…”
InfluentialSelf-citationPharmacotherapy for post traumatic stress disorder (PTSD)
Stein, D. J., Ipser, J. C., Seedat, S., Sager, C., & Amos, T. (2006) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd002795.pub2 · Cited by 519 · see citing works
Pharmacotherapy of Anxiety Disorders: Current and Emerging Treatment Options
Garakani, A., Murrough, J. W., Freire, R. C., Thom, R. P., Larkin, K., Buono, F. D., & Iosifescu, D. V. (2020) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2020.595584 · Cited by 440 · see citing works
“Although not known to be efficacious as a monotherapy (149), DCS at a low dose of 50 mg/day (which is largely anNMDA agonist) has been successfully used in augmentation of exposure therapy or CBT, including reducing anxiety in persons performing cognitive tasks (150) and facilitating declarative learning (151) by redu…”
MethodSingewald, N., Schmuckermair, C., Whittle, N., Holmes, A., & Ressler, K. J. (2015) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2014.12.004 · Cited by 390 · see citing works
“…short CBT sessions (Litz et al., 2012), insufficient within-session fear inhibition (Smits et al., 2013b; Tart et al., 2013), chronic DCS treatment (Heresco-Levy et al., 2002), DCS administration outside the therapeutic temporal window (Storch et al., 2007) and subclinical levels of fear…”
BackgroundExtending animal models of fear conditioning to humans
Delgado, M. R., Olsson, A., & Phelps, E. A. (2006) · Biological Psychology · doi:10.1016/j.biopsycho.2006.01.006 · Cited by 366 · see citing works
“For example, one study found poor evidence of the benefits of D-cycloserine using a post-traumatic stress disorder population (Heresco-Levy et al., 2002), although it is worthy to note that no behavioral therapy was used in conjunction with drug application.”
MethodHill, M. N., Patel, S., Carrier, E. J., Rademacher, D. J., Ormerod, B. K., Hillard, C. J., & Gorzalka, B. B. (2005) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300601 · Cited by 363 · see citing works
“…stress disorder and depression, are characterized by problems with forgetting and behavioral flexibility that are manifested as pathological tendencies to ruminate or perseverate on negative information (Bagby et al, 1999; Gold and Chrousos, 2002; Heresco-Levy et al, 2002; King, 2002).”
BackgroundGuastella, A. J., Richardson, R., Lovibond, P. F., Rapee, R. M., Gaston, J. E., Mitchell, P., & Dadds, M. R. (2008) · Biological Psychiatry · doi:10.1016/j.biopsych.2007.11.011 · Cited by 326 · see citing works
Single prolonged stress: toward an animal model of posttraumatic stress disorder
Yamamoto, S., Morinobu, S., Takei, S., Fuchikami, M., Matsuki, A., Yamawaki, S., & Liberzon, I. (2009) · Depression and Anxiety · doi:10.1002/da.20629 · Cited by 308 · see citing works
“demonstrated insufficient efficacy of DCS in the treatment of PTSD.([45]) In that study, DCS was given chronically without exposure therapy.”
MethodBurgdorf, J., Zhang, X.-L., Nicholson, K. L., Balster, R. L., David Leander, J., Stanton, P. K., Gross, A. L., Kroes, R. A., & Moskal, J. R. (2013) · Neuropsychopharmacology · doi:10.1038/npp.2012.246 · Cited by 284 · see citing works
“Neuropsychopharmacology a NMDAR glycine-site partial agonist, has been shown to have therapeutic potential in post-traumatic stress syndrome and schizophrenia but not reliably in depression (Goff et al, 1999; Heresco-Levy et al, 2002a, b, 2006).”
BackgroundThe Role of Glutamate in Anxiety and Related Disorders
Cortese, B. M., & Phan, K. L. (2005) · CNS Spectrums · doi:10.1017/s1092852900010427 · Cited by 231 · see citing works
Yamamoto, S., Morinobu, S., Fuchikami, M., Kurata, A., Kozuru, T., & Yamawaki, S. (2008) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301605 · Cited by 224 · see citing works
“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). This discrepancy could be attributed to procedural difference. Heresco-Levy et al. (2002) used daily chronic dosing without exposure therapy whilst Hofm…”
MethodResultInfluentialde Kleine, R. A., Hendriks, G.-J., Kusters, W. J. C., Broekman, T. G., & van Minnen, A. (2012) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.02.033 · Cited by 220 · see citing works
PTSD and stress sensitisation: A tale of brain and body
Stam, R. (2007) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2006.11.010 · Cited by 211 · see citing works
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Riaza Bermudo-Soriano, C., Perez-Rodriguez, M. M., Vaquero-Lorenzo, C., & Baca-Garcia, E. (2012) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2011.04.010 · Cited by 207 · see citing works
Glutamate dysregulation and glutamatergic therapeutics for PTSD: Evidence from human studies
Averill, L. A., Purohit, P., Averill, C. L., Boesl, M. A., Krystal, J. H., & Abdallah, C. G. (2016) · Neuroscience Letters · doi:10.1016/j.neulet.2016.11.064 · Cited by 184 · see citing works
Facilitation of fear extinction by D-cycloserine: theoretical and clinical implications
Richardson, R., Ledgerwood, L., & Cranney, J. (2004) · Learning & Memory · doi:10.1101/lm.78204 · Cited by 185 · see citing works
“Heresco-Levy et al. (2002) reported the results of a double-blind, cross-over design study with Post-traumatic stress disorder (PTSD) patients.”
BackgroundResultInfluentialPilot controlled trial of d-serine for the treatment of post-traumatic stress disorder
Heresco‐Levy, U., Vass, Á., Bloch, B., Wolosker, H., Dumin, E., Balan, L., Deutsch, L., & Kremer, I. (2009) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145709000339 · Cited by 171 · see citing works
“Previously we assessed in a pilot controlled 4-wk study the effects of DCS (50 mg/d) used as adjuvant to ongoing drug treatment in PTSD (Heresco-Levy et al. 2002).”
Self-citationHarvey, B. H., Stein, D. J., Oosthuizen, F., Brand, L., & Wegener, G. (2003) · Psychopharmacology · doi:10.1007/s00213-004-1836-4 · Cited by 163 · see citing works
“In a recent pilot study, Heresco-Levy et al. (2002) reported on the clinical evidence for the efficacy of d-cycloserine, a partial agonist at the glycine regulatory site on the NMDA receptor, in the treatment of PTSD.”
BackgroundPharmacotherapy of anxiety disorders: A critical review
Koen, N., & Stein, D. J. (2011) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2011.13.4/nkoen · Cited by 151 · see citing works
Pharmacotherapy of PTSD: premises, principles, and priorities.
Ravindran, L. N., & Stein, M. B. (2009) · Brain Research · doi:10.1016/j.brainres.2009.03.037 · Cited by 153 · see citing works
“…or early in the development of PTSD. Similarly, investigators have proposed a role for agents that augment glutamate transmission during psychotherapeutic processes targeted towards enhancing extinction of conditioned fears and traumatic memories (Davis et al., 2006; Heresco-Levy et al., 2002).”
BackgroundPTSD: from neurobiology to pharmacological treatments
Kelmendi, B., Adams, T., Yarnell, S. C., Southwick, S., Abdallah, C., & Krystal, J. (2016) · European Journal of Psychotraumatology · doi:10.3402/ejpt.v7.31858 · Cited by 136 · see citing works
“There is minimal evidence that DCS is efficacious as monotherapy (Heresco-Levy et al., 2002) or as an add-on for standard pharmacological treatments for PTSD (Attari, Rajabi, & Maracy, 2014).”
BackgroundAnalysis of free d-serine in mammals and its biological relevance
Nishikawa, T. (2011) · Journal of Chromatography B · doi:10.1016/j.jchromb.2011.08.030 · Cited by 145 · see citing works
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Olff, M., Langeland, W., Witteveen, A., & Denys, D. (2010) · CNS Spectrums · doi:10.1017/s109285290000047x · Cited by 135 · see citing works
Posttraumatic Stress Disorder and Stress-Related Disorders
Shalev, A. Y. (2009) · Psychiatric Clinics of North America · doi:10.1016/j.psc.2009.06.001 · Cited by 131 · see citing works
Hoskins, M. D., Bridges, J., Sinnerton, R., Nakamura, A., Underwood, J. F. G., Slater, A., Lee, M. R. D., Clarke, L., Lewis, C., Roberts, N. P., et al. (2021) · European Journal of Psychotraumatology · doi:10.1080/20008198.2020.1802920 · Cited by 127 · see citing works
“…et al., 2014; Bartzokis et al., 2005; Batki et al., 2014; Becker et al., 2007; Germain et al., 2012; Golier et al 2012; Hamner et al., 2009, 2000; Heresco-Levy et al., 2002; Jetly et al., 2015; Krystal et al., 2011; Lindley et al., 2007; Ludascher et al., 2015; Manteghi et al., 2014; Monnelly et…”
BackgroundDoes D-cycloserine enhance exposure therapy for anxiety disorders in humans? A meta-analysis
Rodrigues, H., Figueira, I., Lopes, A., Gonçalves, R., Mendlowicz, M. V., Coutinho, E. S. F., & Ventura, P. (2014) · PLoS ONE · doi:10.1371/journal.pone.0093519 · Cited by 109 · see citing works
“Response to treatment was defined as decrease from baseline $10 points on the ClinicianAdministered PTSD Scale (CAPS) and remission was defined as a CAPS severity score ,20.”
BackgroundInfluentialStorch, E. A., Wilhelm, S., Sprich, S. E., Henin, A., Micco, J. A., Small, B. J., Mcguire, J. F., Mutch, P. J., Lewin, A. B., Murphy, T. K., et al. (2016) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2016.1128 · Cited by 107 · see citing works
A systematic review of off-label uses of memantine for psychiatric disorders
Zdanys, K. F., & Tampi, R. R. (2008) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2008.01.008 · Cited by 104 · see citing works
The NMDA Agonist D-Cycloserine Facilitates Fear Memory Consolidation in Humans
Kalisch, R., Holt, B., Petrović, P., Martino, B. D., Klöppel, S., Büchel, C., & Dolan, R. J. (2008) · Cerebral Cortex · doi:10.1093/cercor/bhn076 · Cited by 102 · see citing works
“…rather than enhance, fear responses in human and rat models of conditioned or unconditioned fear (Anthony and Nevins 1993; Karcz-Kubicha et al. 1997; Klodzinska and Chojnacka-Wojcik 2000; Heresco-Levy et al. 2002; Walker et al. 2002; Ressler et al. 2004; Mao et al. 2006; Yang et al. 2007).”
BackgroundPharmacotherapy for post traumatic stress disorder (PTSD)
Williams, T., Phillips, N. J., Stein, D. J., & Ipser, J. (2026) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd002795.pub4 · Cited by 98 · see citing works
Yaka, R., Biegon, A. R., Grigoriadis, N., Simeonidou, C., Grigoriadis, S., Alexandrovich, A. G., Matzner, H., Schumann, J., Trembovler, V., Tsenter, J., et al. (2007) · The FASEB Journal · doi:10.1096/fj.06-7856com · Cited by 93 · see citing works
Pharmacotherapy augmentation strategies in treatment-resistant anxiety disorders
Ipser, J., Carey, P. D., Dhansay, Y., Fakier, N., Seedat, S., & Stein, D. J. (2006) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd005473.pub2 · Cited by 100 · see citing works
Ori, R., Amos, T., Bergman, H., Soares‐Weiser, K., Ipser, J., & Stein, D. J. (2015) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd007803.pub2 · Cited by 93 · see citing works
Siegmund, A., Golfels, F., Finck, C., Halisch, A., Räth, D., Plag, J., & Ströhle, A. (2011) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2011.01.020 · Cited by 89 · see citing works
Kampman, M., Keijsers, G. P. J., Hoogduin, C. A. L., & Hendriks, G.-J. (2002) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.v63n0904 · Cited by 87 · see citing works
Harvey, B. H., & Shahid, M. (2011) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2011.06.014 · Cited by 88 · see citing works
Oosthuizen, F., Wegener, G., & Harvey, B. H. (2005) · Neuropsychiatric Disease and Treatment · doi:10.2147/nedt.1.2.109.61049 · Cited by 81 · see citing works
de Bitencourt, R. M., Pamplona, F. A., & Takahashi, R. N. (2012) · Neuropharmacology · doi:10.1016/j.neuropharm.2012.05.039 · Cited by 79 · see citing works
“Cognitive enhancers have been experimentally and clinically tested in this regard, with interesting results (Heresco-Levy et al., 2002, 2009), and our group and others have long studied cannabinoids as pharmacotherapies that promote behavioral flexibility (in other words, extinction enhancers), as…”
Stress and Amygdala Suppression of Metaplasticity in the Medial Prefrontal Cortex
Richter‐Levin, G., & Maroun, M. (2010) · Cerebral Cortex · doi:10.1093/cercor/bhp311 · Cited by 79 · see citing works
“In contrast, administration of DCS with no exposure therapy is not effective (Heresco-Levy et al. 2002).”
BackgroundNovel treatment approaches for refractory anxiety disorders
Pollack, M. H., Otto, M. W., Roy-Byrne, P. P., Coplan, J. D., Rothbaum, B. O., Simon, N. M., & Gorman, J. M. (2008) · Depression and Anxiety · doi:10.1002/da.20329 · Cited by 77 · see citing works
“In contrast, the NMDA partial agonist, DCS, failed to show efficacy in a small pilot study in patients with PTSD [Heresco-Levy et al., 2002], although, as noted, appeared to enhance the effect of CBT in the treatment of acrophobia and social anxiety disorder [Hofmann et al., 2006; Ressler et al.,…”
ResultInfluentialPharmacotherapy for post traumatic stress disorder (PTSD)
Williams, T., Phillips, N. J., Stein, D. J., & Ipser, J. C. (2022) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd002795.pub3 · Cited by 73 · see citing works
Ho, Y., Ho, S.-C., Pawlak, C. R., & Yeh, K.-Y. (2011) · Behavioural Brain Research · doi:10.1016/j.bbr.2011.01.028 · Cited by 72 · see citing works
“Furthermore, DCS has a good safety profile and is already in use in humans for several indications [20,32,46] and this could significantly facilitate its clinical application in PD patients.”
Scheeringa, M. S., & Weems, C. F. (2014) · Journal of Child and Adolescent Psychopharmacology · doi:10.1089/cap.2013.0106 · Cited by 72 · see citing works
“When the present study began, there had been one positive trial in adults with PTSD, but the DCS was not paired with an exposure therapy (Heresco-Levy et al. 2002); therefore, it was not a true test of using DCS as an adjunct.”
MethodTreatment-refractory posttraumatic stress disorder (TRPTSD): a review and framework for the future
Koek, R. J., Schwartz, H. N., Scully, S., Langevin, J., Spangler, S. L., Korotinsky, A., Jou, K., & Leuchter, A. F. (2016) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2016.01.015 · Cited by 70 · see citing works
Dadds, M. R., & Rhodes, T. (2008) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2008.0029 · Cited by 69 · see citing works
Effects of Chronic D-Serine Elevation on Animal Models of Depression and Anxiety-Related Behavior
Otte, D.-M., Barcena, M. L., Bilkei‐Gorzó, A., Albayram, Ö., Imbeault, S., Jeung, H., Alferink, J., & Zimmer, A. (2013) · PLoS ONE · doi:10.1371/journal.pone.0067131 · Cited by 67 · see citing works
Raut, S. B., Marathe, P. A., van Eijk, L., Eri, R. D., Ravindran, M., Benedek, D. M., Ursano, R. J., Canales, J. J., & Johnson, L. R. (2022) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2022.108195 · Cited by 71 · see citing works
Pharmacologic management of comorbid post-traumatic stress disorder and addictions
Shorter, D. I., Hsieh, J. J., & Kosten, T. R. (2015) · American Journal on Addictions · doi:10.1111/ajad.12306 · Cited by 65 · see citing works
Pharmacotherapy of Post-Traumatic Stress Disorder
Ravindran, L. N., & Stein, M. B. (2009) · Current topics in behavioral neurosciences · doi:10.1007/7854_2009_15 · Cited by 64 · see citing works
Psychopharmacological Issues in the Treatment of TBI and PTSD
McAllister, T. W. (2009) · The Clinical Neuropsychologist · doi:10.1080/13854040903277289 · Cited by 60 · see citing works
NMDA neurotransmission as a critical mediator of borderline personality disorder
Grosjean, B., & Tsai, G. E. (2007) · Journal of Psychiatry and Neuroscience · doi:10.1139/jpn.0710 · Cited by 57 · see citing works
Combining pharmacotherapy with cognitive behavioral therapy: Traditional and new approaches
Davis, M., Barad, M., Otto, M. W., & Southwick, S. (2006) · Journal of Traumatic Stress · doi:10.1002/jts.20149 · Cited by 55 · see citing works
Targeting the Modulation of Neural Circuitry for the Treatment of Anxiety Disorders
Farb, D. H., & Ratner, M. H. (2014) · Pharmacological Reviews · doi:10.1124/pr.114.009126 · Cited by 55 · see citing works
“…neurotransmission are useful in the treatment of certain types of anxiety disorders (e.g., specific phobias) and PTSD wherein re-exposure to a specific salient stimuli can trigger a pathologic response that interferes with activities of daily living (Heresco-Levy et al., 2002; Difede et al., 2014).”
BackgroundOtto, M. W., Basden, S. L., Leyro, T. M., McHugh, R. K., & Hofmann, S. G. (2007) · CNS Spectrums · doi:10.1017/s1092852900020526 · Cited by 53 · see citing works
Wang, A., Liou, Y., Pawlak, C. R., & Ho, Y. (2009) · Behavioural Brain Research · doi:10.1016/j.bbr.2009.11.006 · Cited by 52 · see citing works
Targeting memory processes with drugs to prevent or cure PTSD
Cain, C. K., Maynard, G. D., & Kehne, J. H. (2012) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.2012.704020 · Cited by 50 · see citing works
“Though two pilot studies suggested efficacy as a monotherapy in PTSD [149] and for decreasing negative symptoms as an adjunctive therapy to neuroleptics [150], recent trials presented in abstract form suggest no benefit when combined with cognitive behavior therapy (see Table 2 references).”
ResultAkirav, I., Segev, A., Motanis, H., & Maroun, M. (2009) · Learning & Memory · doi:10.1101/lm.1565109 · Cited by 51 · see citing works
Region-specific alteration in brain glutamate: Possible relationship to risk-taking behavior
Cortese, B. M., Mitchell, T. R., Galloway, M. P., Prevost, K. E., Fang, J., Moore, G. J., & Uhde, T. W. (2009) · Physiology & Behavior · doi:10.1016/j.physbeh.2009.12.005 · Cited by 50 · see citing works
Glutamate and anxiety disorders
Amiel, J. M., & Mathew, S. J. (2007) · Current Psychiatry Reports · doi:10.1007/s11920-007-0033-7 · Cited by 48 · see citing works
Modi, M. E., & Young, L. J. (2011) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.01.026 · Cited by 47 · see citing works
Progress towards understanding the genetics of posttraumatic stress disorder
Voisey, J., Young, R. M., Lawford, B. R., & Morris, C. P. (2014) · Journal of Anxiety Disorders · doi:10.1016/j.janxdis.2014.09.014 · Cited by 46 · see citing works
“A partial agonist of the NMDA receptor, D-cycloserine, has proved successful in the treatment of PTSD (Heresco-Levy et al., 2002).”
BackgroundHarvey, B. H., Bothma, T., Nel, A., Wegener, G., & Stein, D. J. (2005) · Human Psychopharmacology Clinical and Experimental · doi:10.1002/hup.695 · Cited by 47 · see citing works
“, 1999) and more recently has been implicated in PTSD and its treatment (Chambers et al., 1999; Heresco-Levy et al., 2002).”
BackgroundInfluentialNOS1AP is associated with increased severity of PTSD and depression in untreated combat veterans
Lawford, B. R., Morris, C. P., Swagell, C. D., Hughes, I. P., Young, R. M., & Voisey, J. (2012) · Journal of Affective Disorders · doi:10.1016/j.jad.2012.10.013 · Cited by 44 · see citing works
Elevated serum homocysteine levels in male patients with PTSD
Levine, J., Timinsky, I., Vishne, T. H., Dwolatzky, T., Roitman, S., Kaplan, Z., Kotler, M., Sela, B. A., & Spivak, B. (2007) · Depression and Anxiety · doi:10.1002/da.20400 · Cited by 46 · see citing works
“However, a pilot study evaluating the use of this D-cycloserine in patients suffering from PTSD was not conclusive [Garakani et al., 2006; Heresco-Levy et al., 2002].”
ResultBiological and clinical framework for posttraumatic stress disorder
Vermetten, E. H. G. J. M., & Lanius, R. A. (2012) · Handbook of clinical neurology · doi:10.1016/b978-0-444-52002-9.00018-8 · Cited by 48 · see citing works
Targeted treatments in autism and fragile X syndrome
Gürkan, C. K., & Hagerman, R. J. (2012) · Research in Autism · doi:10.1016/j.rasd.2012.05.007 · Cited by 45 · see citing works
Promising Application of D-Amino Acids toward Clinical Therapy
Shi, Y., Hussain, Z., & Zhao, Y. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231810794 · Cited by 43 · see citing works
D-Cycloserine Improves Functional Outcome after Traumatic Brain Injury with Wide Therapeutic Window
Adeleye, A., Shohami, E., Nachman, D., Alexandrovich, A., Trembovler, V., Yaka, R., Shoshan, Y., Dhawan, J., & Biegon, A. (2009) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2009.11.066 · Cited by 45 · see citing works
“…established in clinical use as an antimicrobial drug (Heifets 1994) in some infectious diseases, is also used as a " cognitive enhancer " in several chronic neurological disorders, including Alzheimer's disease and schizophrenia (Duncan et al. 2004; Heresco-Levy et al., 2002; Laake et al., 2002).”
Pharmacotherapy in post-traumatic stress disorder: evidence from randomized controlled trials.
Sullivan, G. M., & Neria, Y. (2009) · PubMed · Cited by 41 · see citing works
Post-traumatic stress disorder: an evaluation of existing pharmacotherapies and new strategies
Zhang, W., & Davidson, J. R. T. (2007) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656566.8.12.1861 · Cited by 40 · see citing works
“(2007) 8(12) 1865 Other interventions that have been studied include negative placebo-controlled trials of inositol [68] , D -cycloserine [69] and a positive controlled trial of repetitive transcranial magnetic stimulation in 24 patients [70] and low-dose (10 mg) cortisol in a placebo-controlled, crossover study in 3…”
BackgroundInvestigational drugs under development for the treatment of PTSD
Ragen, B., Seidel, J., Chollak, C., Pietrzak, R. H., & Neumeister, A. (2015) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.2015.1020109 · Cited by 37 · see citing works
“[90] also found that DCS Investigational drugs under development for the treatment of PTSD”
BackgroundCould Dietary Glutamate Play a Role in Psychiatric Distress?
Kraal, A. Z., Arvanitis, N. R., Jaeger, A. P., & Ellingrod, V. L. (2019) · Neuropsychobiology · doi:10.1159/000496294 · Cited by 35 · see citing works
Krystal, J. H. (2007) · Biological Psychiatry · doi:10.1016/j.biopsych.2007.08.017 · Cited by 34 · see citing works
Harnett, N. G., Wood, K. H., Ference, E. W., Reid, M. A., Lahti, A. C., Knight, A. J., & Knight, D. C. (2017) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2017.04.010 · Cited by 31 · see citing works
Gruenbaum, B. F., Kutz, R., Zlotnik, A. A., & Boyko, M. (2020) · Therapeutic Advances in Psychopharmacology · doi:10.1177/2045125320903951 · Cited by 32 · see citing works
From non-pharmacological treatments for post-traumatic stress disorder to novel therapeutic targets
Hendriksen, H., Olivier, B., & Oosting, R. S. (2014) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2014.03.031 · Cited by 33 · see citing works
Goodman, J., Ressler, R. L., & Packard, M. G. (2017) · Neuroscience · doi:10.1016/j.neuroscience.2017.03.042 · Cited by 30 · see citing works
The role of the dorsal striatum in extinction: A memory systems perspective
Goodman, J., & Packard, M. G. (2018) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2018.02.028 · Cited by 27 · see citing works
“For instance, D-cycloserine boosts the efficacy of extinction-based therapy in post-traumatic stress disorder (Heresco-Levy et al., 2002), drug addiction (Oliveto et al., 2003), obsessive-compulsive disorder (Kushner et al., 2007), and phobia disorders (Ressler et al., 2004).”
BackgroundFujihira, T., Kanematsu, S., Umino, A., Yamamoto, N., & Nishikawa, T. (2007) · Neurochemistry International · doi:10.1016/j.neuint.2007.06.003 · Cited by 27 · see citing works
D-cycloserine in the treatment of posttraumatic stress disorder
Baker, J., Cates, M. E., & Luthin, D. R. (2017) · Mental Health Clinician · doi:10.9740/mhc.2017.03.088 · Cited by 25 · see citing works
Pharmacotherapy of Anxiety Disorders: Current and Emerging Treatment Options
Garakani, A., Murrough, J. W., Freire, R. C. R., Thom, R. P., Larkin, K., Buono, F. D., & Iosifescu, D. V. (2021) · FOCUS The Journal of Lifelong Learning in Psychiatry · doi:10.1176/appi.focus.19203 · Cited by 27 · see citing works
Glutamate-based anxiolytic ligands in clinical trials
Wierońska, J. M., & Pilc, A. (2013) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.2013.803066 · Cited by 20 · see citing works
“Pilot-controlled studies that were performed indicated that DCS may be effective in PTSD patients [76,77].”
BackgroundPharmacotherapy of PTSD: Current Status and Controversies
Sullivan, G. M., & Neria, Y. (2009) · Psychiatric Annals · doi:10.3928/00485713-20090515-01 · Cited by 20 · see citing works
Kelmendi, B., Adams, T. G., Southwick, S. M., Abdallah, C. G., & Krystal, J. H. (2017) · Clinical Psychology Science and Practice · doi:10.1111/cpsp.12202 · Cited by 20 · see citing works
“There is minimal evidence that DCS is efficacious as monotherapy (Heresco-Levy et al., 2002) or as an add-on for standard pharmacological treatments for PTSD (Attari, Rajabi, & Maracy, 2014).”
BackgroundNeurotransmitter, neurohormonal, and neuropeptidal function in stress and PTSD
Bremner, J. D., & Pearce, B. R. (2016) · Wiley eBooks · doi:10.1002/9781118356142.ch9 · Cited by 21 · see citing works
Involvement of NMDA receptor complex in the anxiolytic-like effects of chlordiazepoxide in mice
Poleszak, E., Socała, K., Szopa, A., Wróbel, A., Szewczyk, B., Kasperek, R., Blicharska, E., Nowak, G., & Właź, P. (2011) · Journal of Neural Transmission · doi:10.1007/s00702-011-0585-x · Cited by 18 · see citing works
“…of glycineB sites) (Hood et al. 1989; Emmett et al. 1991) as a potential therapeutic agent for post-traumatic stress disorder and specific phobia (Heresco-Levy et al. 2002; Ressler et al. 2004), and riluzole in the treatment of symptoms obsessive–compulsive disorder (Coric et al. 2005) and…”
Advances in the management of treatment-resistant anxiety disorders
Lanouette, N. M., & Stein, M. B. (2010) · Focus · doi:10.1176/foc.8.4.foc501 · Cited by 15 · see citing works
Co-activation of NR2A and NR2B subunits induces resistance to fear extinction
Leaderbrand, K., Corcoran, K. A., & Radulović, J. (2013) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2013.09.005 · Cited by 15 · see citing works
A role for glutamate in subjective response to smoking and its action on inhibitory control
Nesic, J., Duka, T., Rusted, J. M., & Jackson, A. E. (2011) · Psychopharmacology · doi:10.1007/s00213-011-2189-4 · Cited by 12 · see citing works
“2011), and secondly, evidence exists to show that glutamatergic ligands, including DCS, can modulate cognitive flexibility in humans (Krystal et al. 1998; Heresco-Levy et al. 2002).”
BackgroundPyrkosch, L., Mumm, J., Alt, I., Fehm, L., Fydrich, T., Plag, J., & Ströhle, A. (2018) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2018.08.016 · Cited by 14 · see citing works
Krings, J. G., Wineland, A., Kallogjeri, D., Rodebaugh, T. L., Nicklaus, J. E., Lenze, E. J., & Piccirillo, J. F. (2014) · JAMA Otolaryngology–Head & Neck Surgery · doi:10.1001/jamaoto.2014.2669 · Cited by 13 · see citing works
“TFI score, median (range) 44 (14-65) 47 (10-76) .”
Advances in Psychopharmacology for Anxiety Disorders
Garakani, A., Murrough, J. W., & Iosifescu, D. V. (2014) · FOCUS The Journal of Lifelong Learning in Psychiatry · doi:10.1176/appi.focus.12.2.152 · Cited by 13 · see citing works
Kapfhammer, H. (2014) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2014.16.2/hkapfhammer · Cited by 13 · see citing works
Initial characterization of D-cycloserine for future formulation development for anxiety disorders
Kaushal, G., Ramirez, R., Alambo, D., Taupradist, W., Choksi, K., & Sirbu, C. (2011) · Drug Discoveries & Therapeutics · doi:10.5582/ddt.2011.v5.5.253 · Cited by 13 · see citing works
“Based on its action on the NMDA receptors, recently this drug has been used on numerous clinical trials as an enhancer of exposure therapy for the treatment of anxiety disorders (3-8).”
MethodPharmacologic Treatment of PTSD
Raskind, M. A. (2009) · Humana Press eBooks · doi:10.1007/978-1-60327-329-9_16 · Cited by 14 · see citing works
Pawlak, C. R., Chen, F., Wu, F.-Y., & Ho, Y. (2012) · The Kaohsiung Journal of Medical Sciences · doi:10.1016/j.kjms.2012.02.010 · Cited by 11 · see citing works
Akute und posttraumatische Belastungsstörung
Kapfhammer, H. (2017) · Springer eBooks · doi:10.1007/978-3-662-49295-6_71 · Cited by 2 · see citing works
Novel Treatment Approaches for Refractory Anxiety Disorders
Pollack, M. H., Otto, M. W., Roy‐Byrne, P., Coplan, J. D., Rothbaum, B. O., Simon, N. M., & Gorman, J. M. (2008) · FOCUS The Journal of Lifelong Learning in Psychiatry · doi:10.1176/foc.6.4.foc486 · Cited by 10 · see citing works
Slattery, D. A., Neumann, I. D., Flor, P. J., & Zoicas, I. (2017) · Behavioural Brain Research · doi:10.1016/j.bbr.2017.04.010 · Cited by 10 · see citing works
“For example, augmentation of exposure therapy with D-cycloserine, a ionotropic N-methyl-D-aspartate (NMDA) receptor agonist, was shown to improve some anxiety symptoms in SAD [3,4], PTSD [5,6], panic disorder [7], and acrophobia [8].”
- 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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