Source: Transplantation  |  Posted 7 years ago

High-dose adjuvant glycine may augment the efficacy of the atypical antipsychotics olanzapine and risperidone, suggesting that these agents may affect N-methyl-D-aspartate (NMDA) receptor-mediated neurotransmission differently than does clozapine.

Because of their superior side-effect profile, the newer atypical antipsychotics risperidone and olanzapine are becoming the most widely used medications for schizophrenia. However, these antipsychotics are less effective or completely ineffective against the negative and cognitive symptom domains of schizophrenia.

Clinical trials indicate that glycine site agonists of the NMDA receptors may reduce negative and cognitive symptoms in treatment-resistant schizophrenia when used as adjuvants to conventional antipsychotics; however, previous studies indicate that glycine did not reduce negative or cognitive symptoms in patients taking the atypical antipsychotic clozapine.

Heresco-Levy, with the Hadassah Medical School-Hebrew University, Jerusalem, Israel and colleagues undertook a double-blind, 6-week crossover treatment trial to determine whether glycine would benefit patients taking olanzapine and risperidone. They recruited 17 schizophrenia patients, of whom 12 were taking olanzapine, and 5 were taking risperidone.

Glycine, at a dose of 8 g/kg/day, was added to the patients' ongoing antipsychotic medication. The researchers clinically assessed participants every 2 weeks, and clinical laboratory parameters and amino acid serum levels were monitored.

According to the researchers, glycine treatment was well tolerated and significantly reduced negative symptoms ([]P[] < .0001); furthermore, this improvement remained significant even following covariation for changes in other symptom clusters and extrapyramidal side effects. Significant improvements were also registered in cognitive and positive symptoms.

High posttreatment glycine serum levels were a significant predictor of clinical response.

"This study is the first to examine whether an augmentation strategy of risperidone and olanzapine therapy with high-dose glycine may be therapeutically beneficial," Dr. Heresco Levy and colleagues note.

According to the researchers, following addition of high-dose glycine, patients treated with olanzapine or risperidone undergo negative symptom improvements more similar to those of patients treated with conventional antipsychotics. "This finding strongly suggests that clozapine and the newer atypical antipsychotics may qualitatively or quantitatively differ in their effects on NMDA-mediated neurotransmission, they suggest.