title: Difference in early prediction of antipsychotic non-response between risperidone and olanzapine in the treatment of acute-phase schizophrenia.
abstract: OBJECTIVE
  We examined whether early response/non-response to risperidone according to the Clinical Global Impressions-improvement scale (CGI-I) at 2 weeks could predict subsequent response. This prediction was also applied to olanzapine. We then investigated whether early non-responders (ENRs) to risperidone or olanzapine who switched to the other showed significantly greater improvement, compared with those staying on the initial antipsychotic. We performed a rater-blinded, randomized controlled trial in 18 psychiatric emergency sites. Eligible patients were newly admitted patients with acute schizophrenia. Early response was defined as CGI-I ≤ 3 following 2 weeks of treatment. The primary outcome measure was achievement of remission and ≥ 50% improvement in the Positive and Negative Syndrome Scale at 4 weeks.
  
  
  RESULTS
  At 4 weeks, 53% of risperidone early responders (ERs) went into remission, whereas only 9% of ENRs staying on risperidone (n=11) did (P=0.016). Similarly, at 4 weeks, 81% of risperidone ERs achieved ≥ 50% response, whereas only 9% of ENRs staying on risperidone achieved ≥ 50% response (P < 0.0001). In contrast, 58% of olanzapine ERs (n=33) went into remission, whereas 38% of ENRs staying on olanzapine (n=8) did at 4 weeks (P=0.44). Similarly, 61% of olanzapine ERs achieved ≥ 50% response, whereas 25% of ENRs staying on olanzapine achieved ≥ 50% response (P=0.12). The negative likelihood ratio for the prediction of ≥ 50% response at 4 weeks by early response status to risperidone at 2 weeks was 0.057.
  
  
  CONCLUSIONS
  In newly admitted patients with acute schizophrenia, non-response to risperidone using CGI-I at 2 weeks can predict subsequent response. It looks like there is significant response to olanzapine that doesn't occur until 4 weeks. Thus, clinicians may want to switch to another drug earlier when risperidone is the first drug, and later when olanzapine is the first drug.
authors.affiliation: Department of Psychiatry, Juntendo University Nerima Hospital, Tokyo, Japan. khatta@juntendo.ac.jp
authors.forename: Kotaro
authors.initials: K
authors.lastname: Hatta
authors.forename: Taro
authors.initials: T
authors.lastname: Otachi
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Sudo
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Hayakawa
authors.forename: Yuko
authors.initials: Y
authors.lastname: Ashizawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takebayashi
authors.forename: Naoki
authors.initials: N
authors.lastname: Hayashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hamakawa
authors.forename: Shin
authors.initials: S
authors.lastname: Ito
authors.forename: Reiko
authors.initials: R
authors.lastname: Nakase
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: D000328:Adult; D000704:Analysis of Variance; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D011237:Predictive Value of Tests; D011569:Psychiatric Status Rating Scales; D018967:Risperidone / Q000627:therapeutic use*; D012559:Schizophrenia / Q000188:drug therapy*; D012680:Sensitivity and Specificity
chemical_list: D014150:Antipsychotic Agents; D001569:Benzodiazepines; D018967:Risperidone; D000077152:Olanzapine