The possibility that requiring high-dose olanzapine cannot be explained by pharmacokinetics in the treatment of acute-phase schizophrenia.

We examined clinical characteristics including serum olanzapine concentrations for acute schizophrenia patients who required above conventional doses. We performed a rater-blinded, randomized clinical trial in 12 psychiatric emergency sites. Eligible patients were 18–64 years old and met diagnostic criteria for schizophrenia, acute schizophrenia-like psychotic disorder, or schizoaffective disorder. A total of 42 patients were randomly assigned by means of sealed envelopes to receive risperidone (3–12mg/day; n=20) and olanzapine (10–40mg/day; n=22), with follow-up at 8 weeks. The Negative score of the Positive and Negative Syndrome Scale was significantly higher in patients who required high doses than in patients who responded to conventional doses. Serum olanzapine concentrations at the time of oral 20mg/day could be obtained from 5 out of 7 patients who subsequently required high-dose olanzapine. All values were more than 30ng/mL after 11–16h from dosing to sample collection, and the mean value was 47.876 (S.D. 21.546) ng/mL. Such concentrations are appropriate with respect to a therapeutic range of 20–50ng/mL. The present study has shown evidence that the reason for requiring high-dose olanzapine cannot be explained by pharmacokinetics in the treatment of acute-phase schizophrenia.