Glycine transporter I inhibitor, N-methylglycine (sarcosine), added to clozapine for the treatment of schizophrenia.
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.
Lane
Hsien-Yuan
HY
Department of Psychiatry, China Medical University and Hospital, Taichung, Taiwan.
Huang
Chieh-Liang
CL
Wu
Po-Lun
PL
Liu
Yi-Ching
YC
Chang
Yue-Cune
YC
Lin
Pao-Yen
PY
Chen
Po-Wei
PW
Tsai
Guochuan
G
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
D014150:Antipsychotic Agents; D050487:Glycine Plasma Membrane Transport Proteins; C493268:SLC6A9 protein, human; D003024:Clozapine; D012521:Sarcosine