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

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1-8
Number of pages8
JournalInternational Journal of Neuropsychopharmacology
Volume18
Issue number5
DOIs
Publication statusPublished - 01-03-2015

Fingerprint

Polypharmacy
Antipsychotic Agents
Schizophrenia
Observation
Therapeutics
Chlorpromazine
Prescriptions
Linear Models
History
Quality of Life
Health
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

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

Cite this

@article{8c507e58487e4f1b8a2af4a75a9f742d,
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.",
author = "Yoshio Yamanouchi and Tsuruhei Sukegawa and Ataru Inagaki and Toshiya Inada and Takashi Yoshio and Reiji Yoshimura and Nakao Iwata",
year = "2015",
month = "3",
day = "1",
doi = "10.1093/ijnp/pyu016",
language = "English",
volume = "18",
pages = "1--8",
journal = "International Journal of Neuropsychopharmacology",
issn = "1461-1457",
publisher = "Cambridge University Press",
number = "5",

}

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

In: International Journal of Neuropsychopharmacology, Vol. 18, No. 5, 01.03.2015, p. 1-8.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Evaluation of the individual safe correction of antipsychotic agent polypharmacy in Japanese patients with chronic schizophrenia

T2 - Validation of safe corrections for antipsychotic polypharmacy and the high-dose method

AU - Yamanouchi, Yoshio

AU - Sukegawa, Tsuruhei

AU - Inagaki, Ataru

AU - Inada, Toshiya

AU - Yoshio, Takashi

AU - Yoshimura, Reiji

AU - Iwata, Nakao

PY - 2015/3/1

Y1 - 2015/3/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84931274260&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84931274260&partnerID=8YFLogxK

U2 - 10.1093/ijnp/pyu016

DO - 10.1093/ijnp/pyu016

M3 - Article

VL - 18

SP - 1

EP - 8

JO - International Journal of Neuropsychopharmacology

JF - International Journal of Neuropsychopharmacology

SN - 1461-1457

IS - 5

ER -