title: Antipsychotic switching versus augmentation among early non-responders to risperidone or olanzapine in acute-phase schizophrenia.
abstract: OBJECTIVE
  We examined whether augmentation with olanzapine would be superior to switching to olanzapine among early non-responders (ENRs) to risperidone, and whether augmentation with risperidone would be superior to switching to risperidone among ENRs to olanzapine. We performed a rater-blinded, randomized clinical trial at psychiatric emergency sites. Eligible patients were newly admitted patients with acute schizophrenia. ENRs to the initial antipsychotic (Clinical Global Impressions-Improvement Scale: ≥ 4 at 2 weeks) were allocated to receive either augmentation with or switching to the other antipsychotic (RIS+OLZ vs. RIS-OLZ; OLZ+RIS vs.
  Sixty patients who completed 2 weeks of risperidone treatment were divided into 33 early responders (RIS-ER) and 27 ENRs (RIS+OLZ, n=14; RIS-OLZ, n=13). Although time to treatment discontinuation for any cause was significantly shorter in RIS+OLZ group (54.1 days [95% confidence interval, 41.3-67.0]) than in RIS-ER group (68.7 [61.2-76.2]; P=0.050), it was not significantly shorter in RIS-OLZ group (58.5 [43.1-73.9]) than in RIS-ER group (P=0.19). Sixty patients who completed 2 weeks of olanzapine treatment were divided into 36 early responders (OLZ-ER) and 24 ENRs (OLZ+RIS, n=11; OLZ-RIS, n=13). Although time to treatment discontinuation for any cause was significantly shorter in OLZ-RIS group (56.1days [40.7-71.5]) than in OLZ-ER group (74.9 [68.5-81.3]; P=0.008), it was not significantly shorter in OLZ+RIS group (64.6 [49.6-79.6]) than in OLZ-ER group (P=0.20).
  
  
  CONCLUSIONS
  Despite the lack of pharmacokinetic investigation of dose adequacy in this study, it is possible that switching to olanzapine among ENRs to risperidone might have a small advantage over augmentation with olanzapine, while augmentation with risperidone might have a small advantage over switching to risperidone among ENRs to olanzapine. Further research is required before it would be appropriate to modify routine practice in the direction of these findings.
authors.affiliation: Department of Psychiatry, Juntendo University Nerima Hospital, Tokyo, Japan; Department of Social Psychiatry, National Center of Neurology and Psychiatry, Kodaira, Japan. Electronic address: khatta@juntendo.ac.jp.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Hatta
authors.affiliation: Department of Psychiatry, Gunma Psychiatric Medical Center, Isezaki, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Otachi
authors.affiliation: Department of Psychiatry, The Okehazama Hospital, Toyoake, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Fujita
authors.affiliation: Department of Psychiatry, Asahikawa Keisenkai Hospital, Asahikawa, Japan.
authors.forename: Fumiyoshi
authors.initials: F
authors.lastname: Morikawa
authors.affiliation: Department of Psychiatry, Kumpukai Yamada Hospital, Tokyo, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Ito
authors.affiliation: Department of Psychiatry, National Hospital Organization Hizen Psychiatric Center, Yoshinogari, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Tomiyama
authors.affiliation: Department of Psychiatry, Chiba Psychiatric Medical Center, Chiba, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Abe
authors.affiliation: Department of Psychiatry, Tosa Hospital, Kochi, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Sudo
authors.affiliation: Department of Psychiatry, Saitama Prefectural Psychiatric Hospital, Ina-machi, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takebayashi
authors.affiliation: Department of Psychiatry, Yamanashi Prefectural Kita Hospital, Nirasaki, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Yamashita
authors.affiliation: Department of Psychiatry, Seijin Hospital, Tokyo, Japan.
authors.forename: Shigemasa
authors.initials: S
authors.lastname: Katayama
authors.affiliation: Department of Psychiatry, Mie Prefectural Mental Medical Center, Tsu, Japan.
authors.forename: Reiko
authors.initials: R
authors.lastname: Nakase
authors.affiliation: Department of Psychiatry, Hyogo Prefecture Kofu Hospital, Kobe, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Shirai
authors.affiliation: Department of Psychiatry, Juntendo University Nerima Hospital, Tokyo, Japan.
authors.forename: Chie
authors.initials: C
authors.lastname: Usui
authors.affiliation: Department of Environmental and Preventive Medicine, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakamura
authors.affiliation: Department of Social Psychiatry, National Center of Neurology and Psychiatry, Kodaira, Japan.
authors.forename: Hiroto
authors.initials: H
authors.lastname: Ito
authors.affiliation: Department of Psychiatry, Chiba Psychiatric Medical Center, Chiba, Japan.
authors.forename: Toyoaki
authors.initials: T
authors.lastname: Hirata
authors.affiliation: Department of Psychiatry, Sawa Hospital, Osaka, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Sawa
mesh_terms: D000208:Acute Disease; D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000009:adverse effects / Q000627:therapeutic use*; D057915:Drug Substitution; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007564:Japan; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D011446:Prospective Studies; D011569:Psychiatric Status Rating Scales; D018967:Risperidone / Q000009:adverse effects / Q000627:therapeutic use*; D012559:Schizophrenia / Q000188:drug therapy*; D016037:Single-Blind Method; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D001569:Benzodiazepines; D018967:Risperidone; D000077152:Olanzapine
keywords: Add-on; Combination; Early response; Emergency; Polypharmacy; Randomized clinical trial