Efficacy of high-dose glycine in the treatment of enduring negative symptoms of schizophrenia.
BACKGROUND
Disturbances of N-methyl-D-aspartate (NMDA) receptor-mediated glutamatergic neurotransmission may play an important role in the pathophysiology of negative symptoms of schizophrenia. Glycine, a small nonessential amino acid, functions as an obligatory coagonist at NMDA receptors through its action at a strychnine-insensitive binding site on the NMDA receptor complex. Glycine-induced augmentation of NMDA receptor-mediated neurotransmission may thus offer a potentially safe and feasible approach for ameliorating persistent negative symptoms of schizophrenia.


METHODS
Twenty-two treatment-resistant schizophrenic patients participated in a double-blind, placebo-controlled, 6-week, crossover treatment trial with 0.8 g/kg per day of glycine added to their ongoing antipsychotic medication. Clinical assessments, including the Brief Psychiatric Rating Scale (BPRS), the Positive and Negative Syndrome Scale (PANSS), the Simpson-Angus Scale for Extrapyramidal Symptoms, and the Abnormal Involuntary Movement Scale, were performed biweekly throughout the study. Clinical laboratory values and amino acid serum levels were monitored.


RESULTS
Glycine treatment was well tolerated and induced increased glycine (P=.001) and serine (P=.001) serum levels. Glycine administration resulted in (1) a significant (P<.001) 30%+/-16% reduction in negative symptoms, as measured by the PANSS, and (2) a significant (P<.001) 30%+/-18% improvement in the BPRS total scores. The improvement in negative symptoms was unrelated to alterations in extrapyramidal effects or symptoms of depression. Low pretreatment glycine serum levels significantly predicted (r= 0.80) clinical response.


CONCLUSIONS
These findings support hypoglutamatergic hypotheses of schizophrenia and suggest a novel approach for the pharmacotherapy of negative symptoms associated with this illness.
Heresco-Levy
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Ezrath Nashim-Herzog Memorial Hospital, Department of Psychiatry, Hadassah Medical School-Hebrew University, Jerusalem, Israel. heresco@md2.huji.ac.il
Javitt
D C
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Ermilov
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Mordel
C
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Silipo
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Lichtenstein
M
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D000328:Adult; D000596:Amino Acids / Q000097:blood; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005998:Glycine / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D006760:Hospitalization; D006801:Humans; D008297:Male; D010919:Placebos; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D016896:Treatment Outcome
D000596:Amino Acids; D014150:Antipsychotic Agents; D010919:Placebos; D005998:Glycine