D-serine added to clozapine for the treatment of schizophrenia.
OBJECTIVE
D-Serine is a full agonist at the glycine site on the N-methyl-D-aspartate (NMDA) receptor. Previous administration of D-serine to schizophrenic patients taking nonclozapine antipsychotics improved positive, negative, and cognitive symptoms, whereas the partial agonist D-cycloserine improved negative symptoms of patients taking conventional antipsychotics but worsened symptoms in clozapine-treated patients. To study the difference between full and partial agonists at the NMDA receptor glycine site, the clinical effects of adding D-serine to clozapine were assessed.


METHODS
In a 6-week double-blind trial, 20 schizophrenic patients received placebo or D-serine (30 mg/kg per day) in addition to clozapine. Clinical efficacy, side effects, and serum levels of D-serine were determined every other week.


RESULTS
The patients exhibited no improvement with D-serine, nor did their symptoms worsen, as previously reported with D-cycloserine.


CONCLUSIONS
The results suggest either that clozapine may have an agonistic effect on the NMDA system or that clozapine-treated patients do not respond to D-serine.
Tsai
G E
GE
Laboratory of Molecular and Psychiatric Neuroscience, Mailman Research Center, McLean Hospital, Belmont, MA 02478, USA. Tsaig@McLean.Harvard.edu
Yang
P
P
Chung
L C
LC
Tsai
I C
IC
Tsai
C W
CW
Coyle
J T
JT
D014150:Antipsychotic Agents / Q000627:therapeutic use*; D003024:Clozapine / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005998:Glycine / Q000037:antagonists & inhibitors / Q000187:drug effects; D006801:Humans; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000187:drug effects; D012559:Schizophrenia / Q000188:drug therapy*; D012694:Serine / Q000627:therapeutic use*
D014150:Antipsychotic Agents; D016194:Receptors, N-Methyl-D-Aspartate; D012694:Serine; D003024:Clozapine; D005998:Glycine