Clozapine and norclozapine plasma concentrations and clinical response of treatment-refractory schizophrenic patients

Am J Psychiatry. 1991 Feb;148(2):231-5. doi: 10.1176/ajp.148.2.231.


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.

Method: 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%.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Antipsychotic Agents / therapeutic use
  • Chromatography, High Pressure Liquid
  • Clinical Protocols
  • Clozapine / administration & dosage
  • Clozapine / analogs & derivatives*
  • Clozapine / blood*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Psychiatric Status Rating Scales
  • ROC Curve
  • Schizophrenia / blood
  • Schizophrenia / drug therapy*
  • Schizophrenic Psychology*
  • Sensitivity and Specificity


  • Antipsychotic Agents
  • norclozapine
  • Clozapine