Olanzapine plasma concentrations and clinical response: acute phase results of the North American Olanzapine Trial.
Olanzapine is an atypical antipsychotic that is effective in the treatment of schizophrenia. Olanzapine plasma concentrations > or = 9.3 ng/mL (24 hours postdose) have been identified as a predictor of clinical response in acutely ill patients with schizophrenia. The authors report a receiver operating characteristic (ROC) curve analysis of 12-hour olanzapine concentrations and treatment response from the North American Double-Blind Olanzapine Trial. After a 4- to 7-day placebo lead-in, patients meeting DSM-III-R criteria for schizophrenia were randomly assigned to receive olanzapine, haloperidol, or placebo. Patients who were randomly assigned to receive olanzapine were given daily doses ranging from 2.5 to 17.5 mg/day for up to 6 weeks. Blood samples for the determination of olanzapine plasma concentrations were obtained between 10 and 16 hours (11.7 +/- 1.7 hours) after the last dose was administered. Therapeutic response data and olanzapine concentrations used for analysis were obtained from the endpoint visit for each patient if the patient had been receiving a fixed olanzapine dose for at least the last 2 weeks of the study. Plasma concentrations from previous visits were used if endpoint concentrations were invalid. Response was defined as a > or = 20% reduction in Brief Psychiatric Rating Scale (BPRS) scores and a Clinical Global Impression (CGI) Severity scale score of < or = 3 or a final BPRS score of < or = 35. The final ROC analysis included data from 84 patients and suggested an olanzapine concentration > or = 23.2 ng/mL to be a predictor of therapeutic response. Fifty-two percent of patients with 12-hour olanzapine concentrations > or = 23.2 ng/mL responded, whereas only 25% of patients with concentrations < 23.2 ng/mL responded. Furthermore, an olanzapine concentration > or = 23.2 ng/mL was a predictor of response in the Scale for the Assessment of Negative Symptoms (> or = 20% decrease and endpoint CGI < or = 3). Olanzapine concentrations were found to be a function of olanzapine dose (in milligrams per day) and gender such that prospective olanzapine dosing is feasible. A 12-hour olanzapine plasma concentration of > 23.2 ng/mL was a predictor of therapeutic response in acutely ill patients with schizophrenia. Males required a higher olanzapine dose to reach this threshold concentration than their female counterparts.
Perry
P J
PJ
Department of Psychiatry, College of Medicine, University of Iowa, Iowa City, USA. paul-perry@uiowa.edu
Lund
B C
BC
Sanger
T
T
Beasley
C
C
D000210:Acute-Phase Reaction; D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000097:blood* / Q000627:therapeutic use; D001569:Benzodiazepines; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009656:North America; D000077152:Olanzapine; D017063:Outcome Assessment, Health Care; D010890:Pirenzepine / Q000031:analogs & derivatives* / Q000097:blood* / Q000627:therapeutic use; D012559:Schizophrenia / Q000097:blood / Q000188:drug therapy*; D016896:Treatment Outcome
D014150:Antipsychotic Agents; D001569:Benzodiazepines; D010890:Pirenzepine; D000077152:Olanzapine