Double-blind, placebo-controlled, crossover trial of glycine adjuvant therapy for treatment-resistant schizophrenia

Br J Psychiatry. 1996 Nov;169(5):610-7. doi: 10.1192/bjp.169.5.610.


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 improvements 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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antipsychotic Agents / administration & dosage*
  • Antipsychotic Agents / adverse effects
  • Brain / drug effects
  • Cross-Over Studies
  • Depression / diagnosis
  • Depression / drug therapy
  • Depression / psychology
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Glycine / administration & dosage*
  • Glycine / adverse effects
  • Humans
  • Male
  • Middle Aged
  • Psychiatric Status Rating Scales
  • Receptors, N-Methyl-D-Aspartate / drug effects
  • Schizophrenia / diagnosis
  • Schizophrenia / drug therapy*
  • Schizophrenic Psychology*


  • Antipsychotic Agents
  • Receptors, N-Methyl-D-Aspartate
  • Glycine