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Efficacy of high-dose glycine in the treatment of enduring negative symptoms of schizophrenia.

AbstractBACKGROUND:
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.
CONCLUSION:
These findings support hypoglutamatergic hypotheses of schizophrenia and suggest a novel approach for the pharmacotherapy of negative symptoms associated with this illness.
AuthorsU Heresco-Levy, D C Javitt, M Ermilov, C Mordel, G Silipo, M Lichtenstein
JournalArchives of general psychiatry (Arch Gen Psychiatry) Vol. 56 Issue 1 Pg. 29-36 (Jan 1999) ISSN: 0003-990X [Print] United States
PMID9892253 (Publication Type: Clinical Trial, Controlled Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Amino Acids
  • Antipsychotic Agents
  • Placebos
  • Glycine
Topics
  • Adult
  • Amino Acids (blood)
  • Antipsychotic Agents (administration & dosage, therapeutic use)
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Glycine (administration & dosage, blood, therapeutic use)
  • Hospitalization
  • Humans
  • Male
  • Placebos
  • Psychiatric Status Rating Scales
  • Schizophrenia (blood, diagnosis, drug therapy)
  • Schizophrenic Psychology
  • Treatment Outcome

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