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 subtype of the glutamate receptor, added to conventional neuroleptics for schizophrenic patients with prominent negative symptoms.


METHODS
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.
Goff
D C
DC
Erich Lindemann Mental Health Center, Department of Psychiatry, Massachusetts General Hospital, Boston.
Tsai
G
G
Manoach
D S
DS
Coyle
J T
JT
D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D003523:Cycloserine / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D018690:Excitatory Amino Acid Agonists / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D018697:Nootropic Agents / Q000627:therapeutic use; D011569:Psychiatric Status Rating Scales; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D016896:Treatment Outcome
D014150:Antipsychotic Agents; D018690:Excitatory Amino Acid Agonists; D018697:Nootropic Agents; D016194:Receptors, N-Methyl-D-Aspartate; D003523:Cycloserine