Adjunctive high-dose glycine in the treatment of schizophrenia.

Glycine is an agonist at brain N-methyl-D-aspartate receptors and crosses the blood-brain barrier following high-dose oral administration. In a previous study, significant improvements in negative and cognitive symptoms were observed in a group of 21 schizophrenic patients receiving high-dose glycine in addition to antipsychotic treatment. This study evaluated the degree to which symptom improvements might be related to alterations in antipsychotic drug levels in an additional group of 12 subjects. Glycine treatment was associated with an 8-fold increase in serum glycine levels, similar to that observed previously. A significant 34% reduction in negative symptoms was observed during glycine treatment. Serum antipsychotic levels were not significantly altered. Significant clinical effects were observed despite the fact that the majority of subjects were receiving atypical antipsychotics (clozapine or olanzapine). As in earlier studies, improvement persisted following glycine discontinuation.

[1]  D. Goff,et al.  Placebo-controlled trial of glycine added to clozapine in schizophrenia. , 2000, The American journal of psychiatry.

[2]  J. Krystal,et al.  IV glycine and oral d-cycloserine effects on plasma and CSF amino acids in healthy humans , 2000, Biological Psychiatry.

[3]  J. Coyle,et al.  D-serine added to clozapine for the treatment of schizophrenia. , 1999, The American journal of psychiatry.

[4]  R. Roth,et al.  The Neuropsychopharmacology of Phencyclidine: From NMDA Receptor Hypofunction to the Dopamine Hypothesis of Schizophrenia , 1999, Neuropsychopharmacology.

[5]  D. Javitt,et al.  Double-blind, placebo-controlled, crossover trial of D-cycloserine adjuvant therapy for treatment-resistant schizophrenia. , 1998, The international journal of neuropsychopharmacology.

[6]  B. Sokolov,et al.  Expression of NMDAR1, GluR1, GluR7, and KA1 Glutamate Receptor mRNAs Is Decreased in Frontal Cortex of “Neuroleptic‐Free” Schizophrenics: Evidence on Reversible Up‐Regulation by Typical Neuroleptics , 1998, Journal of neurochemistry.

[7]  Nicholas Lange,et al.  D-serine added to antipsychotics for the treatment of schizophrenia , 1998, Biological Psychiatry.

[8]  J. Krystal,et al.  The NMDA antagonist model for schizophrenia: promise and pitfalls. , 1998, Pharmacopsychiatry.

[9]  S. Hirsch,et al.  A Pivotal Role for Glutamate in the Pathogenesis of Schizophrenia, and Its Cognitive Dysfunction , 1997, Pharmacology Biochemistry and Behavior.

[10]  J. Coyle,et al.  D-cycloserine added to clozapine for patients with schizophrenia. , 1996, The American journal of psychiatry.

[11]  D. Javitt,et al.  Double-Blind, Placebo-Controlled, Crossover Trial of Glycine Adjuvant Therapy for Treatment-Resistant Schizophrenia , 1996, British Journal of Psychiatry.

[12]  D. Javitt,et al.  Preliminary investigation of high-dose oral glycine on serum levels and negative symptoms in schizophrenia: an open-label trial , 1996, Biological Psychiatry.

[13]  J. Weissenbach,et al.  A linkage study of the N-methyl-D-aspartate receptor subunit gene loci and schizophrenia in southern African Bantu-speaking families. , 1996 .

[14]  Joseph T. Coyle,et al.  The Glutamatergic Dysfunction Hypothesis for Schizophrenia , 1996, Harvard review of psychiatry.

[15]  J. Olney,et al.  Glutamate receptor dysfunction and schizophrenia. , 1995, Archives of general psychiatry.

[16]  T. Gillespie,et al.  Analysis of olanzapine in human plasma utilizing reversed-phase high-performance liquid chromatography with electrochemical detection. , 1995, Journal of chromatography. B, Biomedical applications.

[17]  D. Javitt,et al.  Amelioration of negative symptoms in schizophrenia by glycine. , 1994, The American journal of psychiatry.

[18]  D. Javitt,et al.  Recent advances in the phencyclidine model of schizophrenia. , 1991, The American journal of psychiatry.

[19]  T. Cooper,et al.  A highly sensitive and specific radioimmunoassay for quantitation of plasma fluphenazine. , 1988, Journal of pharmaceutical sciences.

[20]  G. Bianchetti,et al.  Rapid and sensitive method for determination of haloperidol in human samples using nitrogen-phosphorus selective detection. , 1978, Journal of chromatography.

[21]  J. Coyle,et al.  A placebo-controlled trial of D-cycloserine added to conventional neuroleptics in patients with schizophrenia. , 1999, Archives of general psychiatry.

[22]  S. Potkin,et al.  Effect of clozapine and adjunctive high-dose glycine in treatment-resistant schizophrenia. , 1999, The American journal of psychiatry.

[23]  D. Javitt,et al.  Efficacy of high-dose glycine in the treatment of enduring negative symptoms of schizophrenia. , 1999, Archives of general psychiatry.

[24]  D. Javitt,et al.  The role of excitatory amino acids in neuropsychiatric illness. , 1990, The Journal of neuropsychiatry and clinical neurosciences.

[25]  G. Simpson,et al.  Clozapine plasma levels and convulsions. , 1978, The American journal of psychiatry.