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Dose-finding trial of D-cycloserine added to neuroleptics for negative symptoms in schizophrenia
D C Goff1, G Tsai, D S Manoach
1Erich Lindemann Mental Health Center, Department of Psychiatry, Massachusetts General Hospital, Boston.
Objective:
The authors conducted a dose-finding study of D-cycloserine, a partial agonist at the glycine site of the N-methyl-D-aspartate subtype of the glutamate receptor, added to conventional neuroleptics for schizophrenic patients with prominent negative symptoms.
Method:
Nine patients with schizophrenia completed consecutive 2-week trials of placebo and four doses of D-cycloserine. Clinical assessments were videotaped 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 reduction (mean = 21%, SD = 28%) in negative symptoms and significantly improved reaction time as measured by Sternberg's Item Recognition Paradigm, a test mediated in part by prefrontal cortex.
Conclusions:
This preliminary evidence suggests that D-cycloserine may improve negative symptoms and cognitive deficits over a narrow dose range when added to conventional antipsychotic agents.