Double-blind study of clozapine dose response in chronic schizophrenia.
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.
Simpson
G M
GM
Medical College of Pennsylvania/Hahnemann University, Philadelphia, USA. gsimpson@hsc.usc.edu
Josiassen
R C
RC
Stanilla
J K
JK
de Leon
J
J
Nair
C
C
Abraham
G
G
Odom-White
A
A
Turner
R M
RM
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
D014150:Antipsychotic Agents; D003024:Clozapine; D006220:Haloperidol