DOUBLE-BLIND, PLACEBO-CONTROLLED, CROSSOVER TRIAL OF GLYCINE ADJUVANTTHERAPY 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 rec eptor. Glycine potentiates NMDA receptor-mediated neurotransmission, i ndicating that it may serve as an effective therapeutic agent in the t reatment of schizophrenia. Method. Eleven treatment-resistant patients with chronic schizophrenia completed a double-blind, placebo-controll ed, six-week, randomly assigned, crossover treatment trial of 0.8 g/kg body weight/day of glycine, added to their prior antipsychotic treatm ent. Results. Glycine was well tolerated, resulted in significantly in creased serum glycine levels and induced a mean 36 (7%) reduction in n egative symptoms (P <0.0001). Significant improvments were also induce d in depressive and cognitive symptoms. The greatest reduction in nega tive symptoms was registered in the patients who had the lowest baseli ne serum glycine levels. Conclusions. These results extend previous fi ndings and suggest an additional approach to the pharmacotherapy of ne gative symptoms and cognitive deficits in schizophrenia.