DOSE-FINDING TRIAL OF D-CYCLOSERINE ADDED TO NEUROLEPTICS FOR NEGATIVE SYMPTOMS IN SCHIZOPHRENIA

Objective: The authors conducted a dose-finding study of D-cycloserine , a partial agonist at the glycine site of the N-methyl-D-aspartate su btype of the glutamate receptor, added to conventional neuroleptics fo r schizophrenic patients with prominent negative symptoms. Method: Nin e patients with schizophrenia completed consecutive 2-week trials of p lacebo and four doses of o-cycloserine. Clinical assessments were vide otaped and were scored by a rater who was blind to temporal sequence. Results: D-Cycloserine at a dose of 50 mg/day produced a significant r eduction (mean=21%, SD=28%) in negative symptoms and significantly imp roved reaction time as measured by Sternberg's Item Recognition Paradi gm, a test mediated in part by prefrontal cortex. Conclusions: This pr eliminary evidence suggests that o-cycloserine may improve negative sy mptoms and cognitive deficits over a narrow dose range when added to c onventional antipsychotic agents.