D-Cycloserine added to risperidone in patients with primary negative symptoms of schizophrenia.
BACKGROUND
D-Cycloserine, a partial agonist at the glycine recognition site of the NMDA receptor has previously been shown to improve negative symptoms when added to conventional antipsychotics and to worsen negative symptoms when added to clozapine. The purpose of this study was to examine the effects of D-cycloserine when added to risperidone on negative symptoms of schizophrenia.


METHODS
Ten patients with schizophrenia who were treated with risperidone completed consecutive two 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 50mg/day was associated with significant reduction in negative symptoms (mean=10%). Ratings of depression, extrapyramidal side effects, and cognitive function were unchanged. Serum concentrations of glutamate and serine increased significantly on this dose of D-cycloserine.


CONCLUSIONS
This preliminary study suggests that combination of D-cycloserine, 50mg/day, with risperidone may improve negative symptoms of schizophrenia over a narrow dose range. The degree of improvement appears to be intermediate between improvement of negative symptoms observed with combination of D-cycloserine with conventional antipsychotics and worsening of negative symptoms observed with combination of D-cycloserine with clozapine in previous trials of identical design.
Evins
A Eden
AE
Harvard Medical School and the Schizophrenia Research Program of the Massachusetts General Hospital, Freedom Trail Clinic, 25 Staniford Street, Boston, MA 02114, USA. a_eden_evans@hms.harvard.edu
Amico
Ed
E
Posever
Thomas A
TA
Toker
Rob
R
Goff
Donald C
DC
D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D003523:Cycloserine / Q000008:administration & dosage* / Q000009:adverse effects; D003863:Depression / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D018967:Risperidone / Q000009:adverse effects*; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D016896:Treatment Outcome
D014150:Antipsychotic Agents; D003523:Cycloserine; D018967:Risperidone