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 greater than or equal to 9.3 ng/mL, (24 hours postdose) have been identified as a predictor of clini cal response in acutely ill patients with schizophrenia. The authors report a receiver operating characteristic (ROC) curve analysis of 12-hour olanza pine concentrations and treatment response from the North American Double-B lind Olanzapine Trial. After a 4- to 7-day placebo lead-in, patients meetin g DSM-III-R criteria for schizophrenia were randomly assigned to receive ol anzapine, haloperidol, or placebo. Patients who were randomly assigned to r eceive olanzapine were given daily doses ranging hom 2.5 to 17.5 mg/day for up to 6 weeks. Blood samples for the determination of olanzapine plasma co ncentrations mere obtained between 10 and 16 hours (11.7 +/- 1.7 hours) aft er 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 previou s visits were used if endpoint concentrations were invalid. Response was de fined as a greater than or equal to 20%, reduction in Brief Psychiatric Rat ing Scale (BPRS) scores and a Clinical Global Impression (CGI) Severity sca le score of less than or equal to3 or a final BPRS score of less than or eq ual to 35, The final ROC analysis included data from 84 patients and sugges ted an olanzapine concentration greater than or equal to 23.2 ng/mL to be a predictor of therapeutic response, Fifty-two percent of patients with 12-h our olanzapine concentrations greater than or equal to 23.2 ng/mL responded , whereas only 25% of patients with concentrations <23.2 ng/mL responded. F urthermore, an olanzapine concentration <greater than or equal to>23.2 ng/m L was a predictor of response in the Scale for the Assessment of Negative S ymptoms (greater than or equal to 20% decrease and endpoint CGI less than o r equal to3), Olanzapine concentrations were found to be a function of olan zapine dose (in milligrams per day) and gender such that prospective olanza pine 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 thres hold concentration than their female counterparts.