High-dose glycine added to olanzapine and risperidone for the treatment of schizophrenia

Biol Psychiatry. 2004 Jan 15;55(2):165-71. doi: 10.1016/s0006-3223(03)00707-8.


Background: Clinical trials indicate that glycine site agonists of the N-methyl-D-aspartate (NMDA) receptors may reduce negative and cognitive symptoms in treatment-resistant schizophrenia when used as adjuvants to conventional antipsychotics but possibly not to clozapine. In this study, we assessed whether high-dose glycine may also be therapeutically beneficial when added to olanzapine and risperidone treatment.

Methods: Seventeen olanzapine- or risperidone-treated schizophrenia patients participated in a double-blind, placebo-controlled, 6-week crossover treatment trial with.8 g/kg/day glycine added to their ongoing antipsychotic medication. Clinical assessments were performed biweekly throughout the study. Clinical laboratory parameters and amino acid serum levels were monitored.

Results: Glycine treatment was well tolerated and resulted in a significant (p <.0001) 23% +/- 8% reduction in negative symptoms. Significant improvements were also registered in cognitive and positive symptoms. The negative symptoms improvement remained significant even following covariation for changes in other symptom clusters and extrapyramidal side effects. High posttreatment glycine serum levels significantly predicted (r =.60) clinical response.

Conclusions: These findings indicate that the efficacy of olanzapine and risperidone may be augmented using high-dose adjuvant glycine treatment and suggest that these atypical antipsychotics may affect NMDA receptor-mediated neurotransmission differently than clozapine.

Publication types

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

MeSH terms

  • Adult
  • Antipsychotic Agents / therapeutic use*
  • Behavioral Symptoms
  • Benzodiazepines
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Glycine / administration & dosage
  • Glycine / blood
  • Glycine / therapeutic use*
  • Humans
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Olanzapine
  • Pirenzepine / analogs & derivatives*
  • Pirenzepine / therapeutic use*
  • Risperidone / therapeutic use*
  • Schizophrenia / blood
  • Schizophrenia / drug therapy*
  • Serine / blood
  • Time Factors
  • Treatment Outcome


  • Antipsychotic Agents
  • Benzodiazepines
  • Pirenzepine
  • Serine
  • Risperidone
  • Olanzapine
  • Glycine