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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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Glutamate as a therapeutic target in psychiatric disorders
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“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
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
“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
“…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
“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
“…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
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 316
“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
“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
Yamamoto, S., Morinobu, S., Fuchikami, M., Kurata, A., Kozuru, T., & Yamawaki, S. (2008) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301605 · Cited by 224
“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
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
New perspectives in glutamate and anxiety
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
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 198
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
“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
“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 165
“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
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
“…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
“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
A psychobiological rationale for oxytocin in the treatment of posttraumatic stress disorder
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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 142
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
“…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
“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 111
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 105
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
“…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 97
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 97
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 103
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“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
“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
“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 96
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 73
“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
“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 74
Dadds, M. R., & Rhodes, T. (2008) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2008.0029 · Cited by 69
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
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 74
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Shorter, D. I., Hsieh, J. J., & Kosten, T. R. (2015) · American Journal on Addictions · doi:10.1111/ajad.12306 · Cited by 65
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
Psychopharmacological Issues in the Treatment of TBI and PTSD
McAllister, T. W. (2009) · The Clinical Neuropsychologist · doi:10.1080/13854040903277289 · Cited by 62
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
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
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
“…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
Wang, A., Liou, Y., Pawlak, C. R., & Ho, Y. (2009) · Behavioural Brain Research · doi:10.1016/j.bbr.2009.11.006 · Cited by 52
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
“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
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
Glutamate and anxiety disorders
Amiel, J. M., & Mathew, S. J. (2007) · Current Psychiatry Reports · doi:10.1007/s11920-007-0033-7 · Cited by 50
Modi, M. E., & Young, L. J. (2011) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.01.026 · Cited by 47
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 49
“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
“, 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
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
“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 50
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
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 44
d-Cycloserine improves functional outcome after traumatic brain injury with wide therapeutic window
Adeleye, A. O., Shohami, E., Nachman, D., Alexandrovich, A. G., Trembovler, V., Yaka, R., Shoshan, Y., Dhawan, J., & Biegon, A. R. (2009) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2009.11.066 · Cited by 41
“…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.
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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
“(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
“[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
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From non-pharmacological treatments for post-traumatic stress disorder to novel therapeutic targets
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The role of the dorsal striatum in extinction: A memory systems perspective
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“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).”
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D-cycloserine in the treatment of posttraumatic stress disorder
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Pharmacotherapy of Anxiety Disorders: Current and Emerging Treatment Options
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Glutamate-based anxiolytic ligands in clinical trials
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“Pilot-controlled studies that were performed indicated that DCS may be effective in PTSD patients [76,77].”
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Sullivan, G. M., & Neria, Y. (2009) · Psychiatric Annals · doi:10.3928/00485713-20090515-01 · Cited by 20
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“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 22
Involvement of NMDA receptor complex in the anxiolytic-like effects of chlordiazepoxide in mice
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“…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
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Co-activation of NR2A and NR2B subunits induces resistance to fear extinction
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A role for glutamate in subjective response to smoking and its action on inhibitory control
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“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).”
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“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
Kapfhammer, H. (2014) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2014.16.2/hkapfhammer · Cited by 13
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
“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
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Akute und posttraumatische Belastungsstörung
Kapfhammer, H. (2017) · Springer eBooks · doi:10.1007/978-3-662-49295-6_71 · Cited by 11
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 9
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
“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].”
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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