Glycine Transporter I Inhibitor, N-methylglycine (Sarcosine), Added to Clozapine for the Treatment of Schizophrenia

• Published in: Biological psychiatry (1969) 2006-09, Vol.60 (6), p.645-649
• Main Authors: Lane, Hsien-Yuan, Huang, Chieh-Liang, Wu, Po-Lun, Liu, Yi-Ching, Chang, Yue-Cune, Lin, Pao-Yen, Chen, Po-Wei, Tsai, Guochuan
• Format: Article
• Language: English
• Subjects: Adult; Antipsychotic Agents - therapeutic use; Clozapine - therapeutic use; Double-Blind Method; Drug Therapy, Combination; Female; Glutamate; Glycine Plasma Membrane Transport Proteins - antagonists & inhibitors; GlyT-1; Humans; Male; Middle Aged; N-methyl-D-aspartate; Neuropsychological Tests - statistics & numerical data; Psychiatric Status Rating Scales - statistics & numerical data; sarcosine; Sarcosine - therapeutic use; schizophrenia; Schizophrenia - drug therapy; Time Factors; treatment; Treatment Outcome
• ISSN: 0006-3223; 1873-2402
• DOI: 10.1016/j.biopsych.2006.04.005

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. 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. 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. 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.