title: Double-blind study of clozapine dose response in chronic schizophrenia.
abstract: OBJECTIVE
  This study explored the relative efficacy of three different doses of clozapine.
  
  
  METHODS
  Fifty patients who met Kane et al.'s criteria for treatment-refractory schizophrenia or schizoaffective disorder were studied. All subjects were randomly assigned to 100, 300, or 600 mg/day of clozapine for 16 weeks of double-blind treatment. Forty-eight patients completed this first 16 weeks. Of the 50 patients, 36 went on to second and third 16-week trials of double-blind treatment at the remaining doses.
  
  
  RESULTS
  Four subjects (8%) responded to the first 16-week condition, and one subject (2%) responded to the next 16-week crossover condition. A chi-square comparison of the response rates from the three dose groups failed to show a significant effect. An analysis of variance (ANOVA) comparison of Brief Psychiatric Rating Scale-Anchored (BPRS-A) total change scores from baseline to last observation carried forward showed a significant dose effect (600>300>100 mg/day) at 16 weeks of treatment. A crossover ANOVA of the BPRS-A total scores from the 48-week study also showed that the main effect for dose was highly significant; the 100-mg/day dose gave the higher (poorer) values, and the 300- and 600-mg/ day doses gave equal (better) values. Gender played a role in clinical response to treatment at 100 mg/day.
  
  
  CONCLUSIONS
  Clozapine treatment at 100 mg/day was less effective than at 300 or 600 mg/day. At 100 mg/day, women responded better than did men. The 600 mg/day group had the best results, but an occasional patient required up to 900 mg/day. Overall response rates were lower than expected.
authors.affiliation: Medical College of Pennsylvania/Hahnemann University, Philadelphia, USA. gsimpson@hsc.usc.edu
authors.forename: G M
authors.initials: GM
authors.lastname: Simpson
authors.forename: R C
authors.initials: RC
authors.lastname: Josiassen
authors.forename: J K
authors.initials: JK
authors.lastname: Stanilla
authors.forename: J
authors.initials: J
authors.lastname: de Leon
authors.forename: C
authors.initials: C
authors.lastname: Nair
authors.forename: G
authors.initials: G
authors.lastname: Abraham
authors.forename: A
authors.initials: A
authors.lastname: Odom-White
authors.forename: R M
authors.initials: RM
authors.lastname: Turner
mesh_terms: D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D010054:Brief Psychiatric Rating Scale / Q000706:statistics & numerical data; D003024:Clozapine / Q000008:administration & dosage / Q000627:therapeutic use*; D003430:Cross-Sectional Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006220:Haloperidol / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D008297:Male; D011618:Psychotic Disorders / Q000188:drug therapy / Q000523:psychology; D012559:Schizophrenia / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D003024:Clozapine; D006220:Haloperidol