A Pilot Randomized, Placebo-Controlled Trial of Glycine for Treatment of Schizophrenia and Alcohol Dependence

Abstract

Objectives: The hypofunctioning of N-methyl-D-aspartate (NMDA) receptors are thought to play an important role in the pathophysiology of schizophrenia. The augmentation of the glutamatergic system through the NMDA receptor may attenuate alcohol craving and use. This study was designed to evaluate the efficacy of glycine, an agonist of the glycine B co-agonist site of the NMDA receptor on alcohol consumption and cravings as well as on negative symptoms in schizophrenia. Methods: Participants (N = 20) were given 0.8 g/kg glycine or matching placebo (provided in bottles with mixed in solution) each week for the duration of the 12-week trial. Primary outcome measures included drinking, craving for alcohol, and symptoms of schizophrenia. Cognitive functioning (attention, concentration, and memory) was also evaluated. Results: Glycine showed no benefit over placebo in the reduction of heavy drinking days or craving for alcohol over a 12-week treatment period. Nor was there an effect on negative symptoms of schizophrenia or on cognitive functioning. Conclusions: Although our study showed no beneficial effect of glycine over placebo, our results are consistent with the largest trial of glycine treatment in schizophrenia. Diagnosed schizophrenia and alcohol dependence might be more difficult to treat because of more severe psychopathology. This is the first study to date to examine an innovative treatment approach with an amino acid, glycine, as potentially acting on both alcohol intake and negative symptoms of schizophrenia.

Keywords:

• Alcohol
• schizophrenia
• glycine
• treatment

Acknowledgments

We wish to thank Erin O’Brien, Jenelle Newcomb, and Kathryn Keegan for their important contributions to this project.

Disclosures

Dr. Petrakis has served as a consultant for Alkermes over the past three years. Other authors report no conflict of interest. The authors alone are responsible for the content and writing of this paper.

Additional information

Funding

Funding sources for this study were provided by the Stanley Foundation (grant # 02T-241) and Veterans Affairs VISN I Mental Illness Research Education and Clinical Center (MIRECC). The funding sources had no role in the study design, collection, analysis or interpretation of the data, writing the manuscript, or the decision to submit the paper for publication.