Clozapine and norclozapine plasma concentrations and clinical response of treatment-refractory schizophrenic patients.
OBJECTIVE
Clozapine, an atypical antipsychotic, has been estimated to be effective in 30% of treatment-refractory schizophrenic patients. The authors hypothesized that if a dose-response relationship was obvious for this drug, the response rate could be significantly amplified.


METHODS
Following an 8-24-day dose titration phase, 29 inpatients with treatment-resistant schizophrenia diagnosed according to DSM-III-R were given a clozapine dose of approximately 400 mg/day for 4 weeks; blood samples were obtained weekly during this period.


RESULTS
A receiver operator curve demonstrated that the threshold clozapine plasma concentration for therapeutic response was 350 ng/ml. Sixty-four percent of the patients with clozapine plasma concentrations greater than 350 ng/ml responded, whereas only 22% of the patients with concentrations less than 350 ng/ml responded.


CONCLUSIONS
Use of clozapine blood levels as a predictor for treatment response in treatment-refractory schizophrenic patients appears worthwhile, since the measurement's sensitivity for response was 64% and the specificity for nonresponse was 78%.
Perry
P J
PJ
Department of Psychiatry, College of Medicine, University of Iowa, Iowa City.
Miller
D D
DD
Arndt
S V
SV
Cadoret
R J
RJ
D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use; D002851:Chromatography, High Pressure Liquid; D002985:Clinical Protocols; D003024:Clozapine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D012372:ROC Curve; D012559:Schizophrenia / Q000097:blood / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D012680:Sensitivity and Specificity
D014150:Antipsychotic Agents; C058272:norclozapine; D003024:Clozapine