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

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.