Standard and higher dose of olanzapine in patients with schizophrenia or schizoaffective disorder: a randomized, double-blind, fixed-dose study.
The objective of this study was to assess the dose-response relationship of standard and higher doses of olanzapine in a randomized, double-blind, 8-week, fixed-dose study comparing olanzapine 10 (n = 199), 20 (n = 200), and 40 mg/d (n = 200) for patients with schizophrenia or schizoaffective disorder and suboptimal response to current treatment. Patients meeting criteria for antipsychotic treatment resistance were excluded. Dose-response relationship was assessed by linear regression analysis with log-transformed dose (independent variable) and Positive and Negative Syndrome Scale (PANSS) total score (dependent variable). There were no significant dose group differences in patients completing the study (overall, 67.8%). All dose groups showed statistically significant improvement in PANSS total scores from baseline to end point without significant dose-response relationship (P = 0.295). Post hoc analysis of response showed significant interaction between baseline PANSS and dose (P = 0.023), indicating better response at higher doses for patients with higher baseline PANSS. There was a significant dose response for mean change in weight (P = 0.003) with significant difference between the 10- and 40-mg-dose groups (P = 0.002; 1.9 [10 mg/d], 2.3 [20 mg/d], and 3.0 kg [40 mg/d]). There was a significant dose response for change in prolactin (P < 0.001) with a significant difference between each group (-10.5 [10 mg/d], -1.7 [20 mg/d], and 4.9 ng/mL [40 mg/d]; P < or = 0.018). Over 8 weeks, non-treatment-resistant patients with schizophrenia or schizoaffective disorder responded to all 3 doses of olanzapine, without a statistically significant dose-response relationship, suggesting that for many patients with schizophrenia or schizoaffective disorder, particularly those who are mildly or moderately ill, 10 mg/d should be the initial dose of choice.
Kinon
Bruce J
BJ
Eli Lilly and Company, Lilly Corporate Center, Drop Code 4133, Indianapolis, IN 46285, USA. bj_kinon@lilly.com
Volavka
Jan
J
Stauffer
Virginia
V
Edwards
Sara E
SE
Liu-Seifert
Hong
H
Chen
Lei
L
Adams
David H
DH
Lindenmayer
Jean-Pierre
JP
McEvoy
Joseph P
JP
Buckley
Peter F
PF
Lieberman
Jeffrey A
JA
Meltzer
Herbert Y
HY
Wilson
Daniel R
DR
Citrome
Leslie
L
D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D011388:Prolactin / Q000097:blood; D011569:Psychiatric Status Rating Scales; D011618:Psychotic Disorders / Q000188:drug therapy*; D012559:Schizophrenia / Q000188:drug therapy*; D016896:Treatment Outcome; D015430:Weight Gain / Q000187:drug effects
D014150:Antipsychotic Agents; D001569:Benzodiazepines; D011388:Prolactin; D000077152:Olanzapine