title: Evaluation of the individual safe correction of antipsychotic agent polypharmacy in Japanese patients with chronic schizophrenia: validation of safe corrections for antipsychotic polypharmacy and the high-dose method.
abstract: BACKGROUND
  Polypharmacy for schizophrenia treatment is not justified by the available clinical evidence. We evaluated a treatment reduction approach that reduces the dose and number of antipsychotic medications simultaneously prescribed to patients.
  
  
  METHODS
  In a randomized open study of the Safe Correction of Antipsychotic Polypharmacy and High-Dose Prescriptions program funded by the Japanese Ministry of Health, Labour, and Welfare, we evaluated a drug reduction method consisting of a dose reduction intervention performed on 163 patients with schizophrenia for twelve or 24 weeks. One antipsychotic medication was removed each week from each patient's treatment regimen by reducing the dose by 0 to 50 chlorpromazine equivalents. Data on health-related indices of quality of life, clinical symptoms, and risk of side effects were analyzed using a two-way repeated-measures mixed linear model.
  
  
  RESULTS
  Despite a 23% reduction in antipsychotic dose, no differences in outcomes were observed between the dose reduction and observation groups (effect size = 0.001 - 0.085, P = .24-.97), despite high statistical power (1-β = 0.48-0.97). The findings are limited by the nonuniformity of the participants' treatment history, duration, and dose reduction amount. Dose reduction protocol patients exhibited no difference in psychotic symptoms or adverse events compared with the observation group.
  
  
  CONCLUSIONS
  Importantly, the low dropout rate in our study (6.9% of participants withdrew because of patient factors and 23.8% for all secondary reasons) indicates that our "slowly" method is well tolerated. We hope that this approach will result in therapeutic improvements.
authors.affiliation: Department of Social Psychiatry, National Institute of Mental Health, National Center of Neurology and Psychiatry, Kodaira, Japan (Dr Yamanouchi); National Hospital Organization, Tottori Medical Center, Tottori, Japan (Dr Sukegawa); School of International Politics, Economics and Communication, Aoyama Gakuin University, Tokyo, Japan (Dr Inagaki); Seiwa Hospital, Institute of Neuropsychiatry, Tokyo, Japan (Dr Inada); Department of Clinical Pharmacy Faculty of Pharmaceutical Sciences, Toho University, Funabashi, Japan (Dr Yoshio); Department of Psychiatry, University of Occupational and Environmental Health, Kitakyushu, Japan (Dr Yoshimura); Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Japan (Dr Iwata). yamanouchi@ncnp.go.jp.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Yamanouchi
authors.affiliation: Department of Social Psychiatry, National Institute of Mental Health, National Center of Neurology and Psychiatry, Kodaira, Japan (Dr Yamanouchi); National Hospital Organization, Tottori Medical Center, Tottori, Japan (Dr Sukegawa); School of International Politics, Economics and Communication, Aoyama Gakuin University, Tokyo, Japan (Dr Inagaki); Seiwa Hospital, Institute of Neuropsychiatry, Tokyo, Japan (Dr Inada); Department of Clinical Pharmacy Faculty of Pharmaceutical Sciences, Toho University, Funabashi, Japan (Dr Yoshio); Department of Psychiatry, University of Occupational and Environmental Health, Kitakyushu, Japan (Dr Yoshimura); Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Japan (Dr Iwata).
authors.forename: Tsuruhei
authors.initials: T
authors.lastname: Sukegawa
authors.affiliation: Department of Social Psychiatry, National Institute of Mental Health, National Center of Neurology and Psychiatry, Kodaira, Japan (Dr Yamanouchi); National Hospital Organization, Tottori Medical Center, Tottori, Japan (Dr Sukegawa); School of International Politics, Economics and Communication, Aoyama Gakuin University, Tokyo, Japan (Dr Inagaki); Seiwa Hospital, Institute of Neuropsychiatry, Tokyo, Japan (Dr Inada); Department of Clinical Pharmacy Faculty of Pharmaceutical Sciences, Toho University, Funabashi, Japan (Dr Yoshio); Department of Psychiatry, University of Occupational and Environmental Health, Kitakyushu, Japan (Dr Yoshimura); Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Japan (Dr Iwata).
authors.forename: Ataru
authors.initials: A
authors.lastname: Inagaki
authors.affiliation: Department of Social Psychiatry, National Institute of Mental Health, National Center of Neurology and Psychiatry, Kodaira, Japan (Dr Yamanouchi); National Hospital Organization, Tottori Medical Center, Tottori, Japan (Dr Sukegawa); School of International Politics, Economics and Communication, Aoyama Gakuin University, Tokyo, Japan (Dr Inagaki); Seiwa Hospital, Institute of Neuropsychiatry, Tokyo, Japan (Dr Inada); Department of Clinical Pharmacy Faculty of Pharmaceutical Sciences, Toho University, Funabashi, Japan (Dr Yoshio); Department of Psychiatry, University of Occupational and Environmental Health, Kitakyushu, Japan (Dr Yoshimura); Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Japan (Dr Iwata).
authors.forename: Toshiya
authors.initials: T
authors.lastname: Inada
authors.affiliation: Department of Social Psychiatry, National Institute of Mental Health, National Center of Neurology and Psychiatry, Kodaira, Japan (Dr Yamanouchi); National Hospital Organization, Tottori Medical Center, Tottori, Japan (Dr Sukegawa); School of International Politics, Economics and Communication, Aoyama Gakuin University, Tokyo, Japan (Dr Inagaki); Seiwa Hospital, Institute of Neuropsychiatry, Tokyo, Japan (Dr Inada); Department of Clinical Pharmacy Faculty of Pharmaceutical Sciences, Toho University, Funabashi, Japan (Dr Yoshio); Department of Psychiatry, University of Occupational and Environmental Health, Kitakyushu, Japan (Dr Yoshimura); Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Japan (Dr Iwata).
authors.forename: Takashi
authors.initials: T
authors.lastname: Yoshio
authors.affiliation: Department of Social Psychiatry, National Institute of Mental Health, National Center of Neurology and Psychiatry, Kodaira, Japan (Dr Yamanouchi); National Hospital Organization, Tottori Medical Center, Tottori, Japan (Dr Sukegawa); School of International Politics, Economics and Communication, Aoyama Gakuin University, Tokyo, Japan (Dr Inagaki); Seiwa Hospital, Institute of Neuropsychiatry, Tokyo, Japan (Dr Inada); Department of Clinical Pharmacy Faculty of Pharmaceutical Sciences, Toho University, Funabashi, Japan (Dr Yoshio); Department of Psychiatry, University of Occupational and Environmental Health, Kitakyushu, Japan (Dr Yoshimura); Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Japan (Dr Iwata).
authors.forename: Reiji
authors.initials: R
authors.lastname: Yoshimura
authors.affiliation: Department of Social Psychiatry, National Institute of Mental Health, National Center of Neurology and Psychiatry, Kodaira, Japan (Dr Yamanouchi); National Hospital Organization, Tottori Medical Center, Tottori, Japan (Dr Sukegawa); School of International Politics, Economics and Communication, Aoyama Gakuin University, Tokyo, Japan (Dr Inagaki); Seiwa Hospital, Institute of Neuropsychiatry, Tokyo, Japan (Dr Inada); Department of Clinical Pharmacy Faculty of Pharmaceutical Sciences, Toho University, Funabashi, Japan (Dr Yoshio); Department of Psychiatry, University of Occupational and Environmental Health, Kitakyushu, Japan (Dr Yoshimura); Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Japan (Dr Iwata).
authors.forename: Nakao
authors.initials: N
authors.lastname: Iwata
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000009:adverse effects* / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D019338:Polypharmacy; D011600:Psychopharmacology / Q000379:methods*; D011788:Quality of Life / Q000523:psychology; D012559:Schizophrenia / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents
keywords: antipsychotics; clinical trial; polypharmacy; psychopharmacology; schizophrenia