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 schizoph renic patients taking non-clozapine antipsychotics improved positive, negat ive, and cognitive symptoms, whereas the partial agonist D-cycloserine impr oved negative symptoms of patients taking conventional antipsychotics but w orsened symptoms in clozapine-treated patients. To study the difference bet ween full and partial agonists at the NMDA receptor glycine site, the clini cal effects of adding D-serine to clozapine were assessed. Method: In a 6-w eek double-blind trial, 20 schizophrenic patients received placebo or D-ser ine (30 mg/kg per day) in addition to clozapine. Clinical efficacy, side ef fects, and serum levels of D-serine were determined every other week. Resul ts: The patients exhibited no improvement with D-serine, nor did their symp toms worsen, as previously reported with D-cycloserine. Conclusions: The re sults suggest either that clozapine may have an agonistic effect on the NMD A system or that clozapine-treated patients do not respond to D-serine.