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

Yoshio Yamanouchi, Tsuruhei Sukegawa, Ataru Inagaki, Toshiya Inada, Takashi Yoshio, Reiji Yoshimura, Nakao Iwata

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8 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1-8
Number of pages8
JournalInternational Journal of Neuropsychopharmacology
Issue number5
Publication statusPublished - 01-03-2015


All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)

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