title: Glycine transporter I inhibitor, N-methylglycine (sarcosine), added to clozapine for the treatment of schizophrenia.
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.
authors.affiliation: Department of Psychiatry, China Medical University and Hospital, Taichung, Taiwan.
authors.forename: Hsien-Yuan
authors.initials: HY
authors.lastname: Lane
authors.forename: Chieh-Liang
authors.initials: CL
authors.lastname: Huang
authors.forename: Po-Lun
authors.initials: PL
authors.lastname: Wu
authors.forename: Yi-Ching
authors.initials: YC
authors.lastname: Liu
authors.forename: Yue-Cune
authors.initials: YC
authors.lastname: Chang
authors.forename: Pao-Yen
authors.initials: PY
authors.lastname: Lin
authors.forename: Po-Wei
authors.initials: PW
authors.lastname: Chen
authors.forename: Guochuan
authors.initials: G
authors.lastname: Tsai
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D003024:Clozapine / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D050487:Glycine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D012521:Sarcosine / Q000627:therapeutic use*; D012559:Schizophrenia / Q000188:drug therapy*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D050487:Glycine Plasma Membrane Transport Proteins; C493268:SLC6A9 protein, human; D003024:Clozapine; D012521:Sarcosine