The International Journal of Neuropsychopharmacology

Brief Reports

Adjunctive high-dose glycine in the treatment of schizophrenia

Daniel C.  Javitt  a1 a2 a3 c1, Gail  Silipo  a1, Angel  Cienfuegos  a1, Anne-Marie  Shelley  a3, Nigel  Bark  a3, Mohan  Park  a4, Jean-Pierre  Lindenmayer  a4, Ray  Suckow  a1 and Stephen R.  Zukin  a3
a1 Program in Cognitive Neuroscience and Schizophrenia, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, USA
a2 Department of Psychiatry, New York University School of Medicine, New York, NY, USA
a3 Department of Psychiatry/Bronx Psychiatric Center/Albert Einstein College of Medicine, Bronx, NY, USA
a4 Manhattan Psychiatric Center, New York, NY, USA


Glycine is an agonist at brain N-methyl-D-aspartate receptors and crosses the blood–brain barrier following high-dose oral administration. In a previous study, significant improvements in negative and cognitive symptoms were observed in a group of 21 schizophrenic patients receiving high-dose glycine in addition to antipsychotic treatment. This study evaluated the degree to which symptom improvements might be related to alterations in antipsychotic drug levels in an additional group of 12 subjects. Glycine treatment was associated with an 8-fold increase in serum glycine levels, similar to that observed previously. A significant 34% reduction in negative symptoms was observed during glycine treatment. Serum antipsychotic levels were not significantly altered. Significant clinical effects were observed despite the fact that the majority of subjects were receiving atypical antipsychotics (clozapine or olanzapine). As in earlier studies, improvement persisted following glycine discontinuation.

(Received January 10 2001)
(Reviewed April 29 2001)
(Revised May 14 2001)
(Accepted May 23 2001)

Key Words: Cognition; glutamate; negative symptoms; NMDA receptors; schizophrenia.

c1 Address for correspondence: Dr D. C. Javitt, Cognitive Neuroscience and Schizophrenia Program, Nathan Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Orangeburg, NY 10962, USA. Tel.: (845) 398-6534 Fax: (845) 398-6545 E-mail: