title: The possibility that requiring high-dose olanzapine cannot be explained by pharmacokinetics in the treatment of acute-phase schizophrenia.
abstract: 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 (3-12 mg/day; n=20) and olanzapine (10-40 mg/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 30 ng/mL after 11-16 h 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 20-50 ng/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.
authors.affiliation: Department of Psychiatry, Juntendo University Nerima Hospital, Tokyo, Japan. Electronic address: khatta@juntendo.ac.jp.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Hatta
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takebayashi
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Sudo
authors.forename: Shigemasa
authors.initials: S
authors.lastname: Katayama
authors.forename: Masataka
authors.initials: M
authors.lastname: Kasuya
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Shirai
authors.forename: Fumiyoshi
authors.initials: F
authors.lastname: Morikawa
authors.forename: Reiko
authors.initials: R
authors.lastname: Nakase
authors.forename: Masato
authors.initials: M
authors.lastname: Nakamura
authors.forename: Shin
authors.initials: S
authors.lastname: Ito
authors.forename: Hironori
authors.initials: H
authors.lastname: Kuga
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Nakamura
authors.forename: Tohru
authors.initials: T
authors.lastname: Ohnuma
authors.forename: Chie
authors.initials: C
authors.lastname: Usui
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakamura
authors.forename: Toyoaki
authors.initials: T
authors.lastname: Hirata
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Sawa
mesh_terms: D000208:Acute Disease; D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000097:blood*; D001569:Benzodiazepines / Q000008:administration & dosage / Q000097:blood*; D039721:Diagnostic and Statistical Manual of Mental Disorders; D004305:Dose-Response Relationship, Drug; D004637:Emergency Services, Psychiatric; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D011446:Prospective Studies; D011569:Psychiatric Status Rating Scales; D011618:Psychotic Disorders / Q000097:blood / Q000188:drug therapy*; D018967:Risperidone / Q000008:administration & dosage* / Q000627:therapeutic use; D012559:Schizophrenia / Q000097:blood / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D001569:Benzodiazepines; D018967:Risperidone; D000077152:Olanzapine
keywords: Emergency; Negative symptom; Randomized clinical trial; Risperidone; Serum concentration