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Double-Blind, Placebo-Controlled, Crossover Trial of Glycine Adjuvant Therapy for Treatment-Resistant Schizophrenia

Published online by Cambridge University Press:  02 January 2018

Uriel Heresco-Levy ,
Daniel C. Javitt ,
Marina Ermilov ,
Clara Mordel ,
Avraham Horowitz  and
Dalia Kelly
Uriel Heresco-Levy*
Affiliation:
Ezrath Nashim–Herzog Memorial Hospital and Department of Psychiatry, Hadassah Medical School–Hebrew University, Jerusalem, Israel
Daniel C. Javitt
Affiliation:
Nathan S. Kline Institute for Psychiatric Research, and Department of Psychiatry, New York University Medical Center, New York, USA
Marina Ermilov
Affiliation:
Ezrath Nashim–Herzog Memorial Hospital, Jerusalem, Israel
Clara Mordel
Affiliation:
Ezrath Nashim–Herzog Memorial Hospital, Jerusalem, Israel
Avraham Horowitz
Affiliation:
Ezrath Nashim–Herzog Memorial Hospital, Jerusalem, Israel
Dalia Kelly
Affiliation:
Ezrath Nashim–Herzog Memorial Hospital, Jerusalem, Israel
*
Uriel Heresco-Levy, Psychiatry Department, Ezrath Nashim–Herzog Memorial Hospital, P.O. Box 35300, Jerusalem 91351, Israel. Fax: (02) 653 6075
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Abstract

Background

It has been proposed that schizophrenia is associated with underactivity of brain glutamatergic neurotransmission, especially at the level of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor. Glycine potentiates NMDA receptor-mediated neurotransmission, indicating that it may serve as an effective therapeutic agent in the treatment of schizophrenia.

Method

Eleven treatment-resistant patients with chronic schizophrenia completed a double-blind placebo-controlled, six-week, randomly assigned, crossover treatment trial of 0.8 g/kg body weight/day of glycine, added to their prior antipsychotic treatment.

Results

Glycine was well tolerated, resulted in significantly increased serum glycine levels and induced a mean 36 (7%) reduction in negative symptoms (P < 0.0001). Significant improvments were also induced in depressive and cognitive symptoms. The greatest reduction in negative symptoms was registered in the patients who had the lowest baseline serum glycine levels.

Conclusions

These results extend previous findings and suggest an additional approach to the pharmacotherapy of negative symptoms and cognitive deficits in schizophrenia.

Type
Papers
Information
The British Journal of Psychiatry , Volume 169 , Issue 5 , November 1996 , pp. 610 - 617
Copyright
Copyright © Royal College of Psychiatrists, 1996 

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References

American Psychiatric Association (1987) Diagnostic and Statistical Manual of Mental Disorders (3rd edn, revised) (DSM–III–R). Washington, DC: APA.Google Scholar
Carlsson, M. & Carlsson, A. (1990) Schizophrenia: a subcortical neurotransmitter imbalance syndrome? Schizophrenia Bulletin, 16, 425–432.Google Scholar
Cascella, N. G., Macciardi, F., Cavallini, C., et al (1994) D-Cycloserine adjuvant therapy to conventional neuroleptic treatment in schizophrenia: an open-label study. Journal of Neural Transmission – General Section, 95, 105–111.CrossRefGoogle ScholarPubMed
Costa, J., Khaled, E., Sramek, J., et al (1990) An open trial of glycine as an adjunct to neuroleptics in chronic treatment-refractory schizophrenics. Journal of Clinical Psychopharmacology, 10, 71–72.Google Scholar
D'Souza, C., Charney, D. & Krystal, J. (1995) Glycine site agonists of the NMDA receptor a review. CNS Drug Reviews, 1, 227–260.CrossRefGoogle Scholar
Goff, D. C., Tsai, G., Manoach, D. S., et al (1995) Dose-finding trial of D-cycloserine added to neuroleptics for negative symptoms in schizophrenia. American Journal of Psychiatry, 152, 1213–1215.Google Scholar
Guy, W. (ed.) (1976) ECDEU Assessment Manual for Psychopharmacology, pp. 534–537. Washington, DC: US Department of Health, Education and Welfare.Google Scholar
Javitt, D. C. & Zukin, S. R. (1991) Recent advances in the phencyclidine model of schizophrenia. American Journal of Psychiatry, 148, 1301–1308.Google ScholarPubMed
Javitt, D. C., Zylberman, I., Zukin, S. R., et al (1994) Amelioration of negative symptoms in schizophrenia by glycine. American Journal of Psychiatry, 151, 1234–1236.Google Scholar
Johnson, J. W. & Asher, P. (1987) Glycine potentiates the NMDA response in cultured mouse brain neurones. Nature, 323, 529–531.CrossRefGoogle Scholar
Kay, S. R., Opler, L. A. & Fiszbein, A. (1987) Positive and Negative Syndrome Scale (PANSS) Rating Manual. San Rafael CA: Social and Behavioral Sciences Documents.Google Scholar
Kim, J. S., Kornhuber, H. H., Schmid-Burgk, W., et al (1980) Low cerebrospinal fluid glutamate in schizophrenic patients and a new hypothesis on schizophrenia. Neuroscience Letters, 20, 379–382.CrossRefGoogle Scholar
Krystal, J. H., Karper, L. P., Seibyl, J. P., et al (1994) Subanaesthetic effects of the non-competitive NMDA antagonist, ketamine, in humans: psychomimetic, perceptual, cognitive and neuroendocrine responses. Archives of General Psychiatry, 51, 199–214.CrossRefGoogle Scholar
Leiderman, E., Zylberman, I., Zukin, S. R., et al (1996) Preliminary investigation of high-dose oral glycine on serum levels and negative symptoms in schizophrenia: an open label trial Biological Psychiatry, 39, 213–215.CrossRefGoogle ScholarPubMed
Lindenmayer, J. P., Bbrnstein-Hyman, R. & Grochowski, S. (1994) Five-factor model of schizophrenia. Initial validation. Journal of Nervous and Mental Disease, 182, 631–638.Google Scholar
Oldendorph, W. H. (1971) Brain uptake of radio labelled amino acids, amines and hexoses after arterial injection. American Journal of Physiology, 221, 1629–1639.Google Scholar
Potkin, S. G., Costa, J., Roy, S., et al (1992) Glycine in treatment of schizophrenia – theory and preliminary results. In Novel Antipsychotic Drugs (ed. Meltzer, H. Y.), pp. 179–188. New York: Raven Press.Google Scholar
Rosse, R. B., Thent, S. K., Banay-Schwartz, M., et al (1989) Glycine adjuvant therapy to conventional neuroleptic treatment in schizophrenia: an open-label, pilot study. Clinical Neuropharmacology, 2, 416–424.Google Scholar
Simpson, G. M. & Angus, J. W. S. (1970) A rating scale for extrapyramidal side effects. Acta Psychiatrica Scandinavica, suppl. 212, 11–19.CrossRefGoogle ScholarPubMed
Toth, E. & Lajtha, A. (1986) Antagonism of phencyclidine-induced hyperactivity by glycine in mice. Neurochemical Research, 11, 393–400.CrossRefGoogle ScholarPubMed
Tsai, G., Passani, L. A., Slusher, B. S., et al (1995) Abnormal excitatory neurotransmitter metabolism in schizophrenic brains. Archives of General Psychiatry, 52, 829–836.Google Scholar
Ulas, J. & Cotman, C. W. (1993) Excitatory amino acid receptors in schizophrenia. Schizophrenia Bulletin, 19, 105–117.CrossRefGoogle ScholarPubMed
Waziri, R. (1988) Glycine therapy of schizophrenia. Biological Psychiatry, 23, 210–211.Google Scholar
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