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Am J Psychiatry 1995; 152:1213-1215
Copyright © 1995 by American Psychiatric Association
Dose-finding trial of D-cycloserine added to neuroleptics for negative symptoms in schizophrenia
DC Goff, G Tsai, DS Manoach and JT Coyle
Erich 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.
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