Glycine transporter I inhibitor, N-methylglycine (sarcosine), added to clozapine for the treatment of schizophrenia.

Authors:	Hsien-Yuan Lane, Chieh-Liang Huang, Po-Lun Wu, Yi-Ching Liu, Yue-Cune Chang, Pao-Yen Lin, Po-Wei Chen, Guochuan Tsai
Language:	Eng.
Date:	2006-09-25
Journal:	Biological Psychiatry (0006-3223)
Release:	Biol Psychiatry. 2006 Sep;60(6):645-9
Abstract:	BACKGROUND: Agonists at the N-methyl-D-aspartate (NMDA)-glycine site (D-serine, glycine, D-alanine and D-cycloserine) and glycine transporter-1 (GlyT-1) inhibitor (N-methylglycine, or called sarcosine) both improve the symptoms of stable chronic schizophrenia patients receiving concurrent antipsychotics. Previous studies, however, found no advantage of D-serine, glycine, or D-cycloserine added to clozapine. The present study aims to determine the effects of sarcosine adjuvant therapy for schizophrenic patients receiving clozapine treatment. METHODS: Twenty schizophrenic inpatients enrolled in a 6-week double-blind, placebo-controlled trial of sarcosine (2 g/day) which was added to their stable doses of clozapine. Measures of clinical efficacy and side-effects were determined every other week. RESULTS: Sarcosine produced no greater improvement when co-administered with clozapine than placebo plus clozapine at weeks 2, 4, and 6. Sarcosine was well tolerated and no significant side-effect was noted. CONCLUSIONS: Unlike patients treated with other antipsychotics, patients who received clozapine treatment exhibit no improvement by adding sarcosine or agonists at the NMDA-glycine site. Clozapine possesses particular efficacy, possibly related to potentiation of NMDA-mediated neurotransmission. This may contribute to the clozapine's unique clinical efficacy and refractoriness to the addition of NMDA-enhancing agents.
Copyright:	Biological Psychiatry Department of Psychiatry, China Medical University and Hospital, Taichung, Taiwan.
Full text:	DOI - Biological Psychiatry (DOI) EBSCO - HTML (needs subscription) Elsevier Science - HTML (needs subscription) Swets Information Services - HTML (needs subscription)
Terms:	Adult, Antipsychotic Agents, Clozapine, Double-Blind Method, Drug Therapy, Combination, Female, Glycine Plasma Membrane Transport Proteins, Humans, Male, Middle Aged, Neuropsychological Tests, Psychiatric Status Rating Scales, Sarcosine, Schizophrenia, Time Factors, Treatment Outcome