title: High doses of antipsychotic polypharmacy are related to an increase in serum levels of pentosidine in patients with schizophrenia.
abstract: Carbonyl stress in patients with schizophrenia has been reported to be reflected by an increase in peripheral pentosidine levels. This cohort study tested whether the accumulation of pentosidine was related to the disease severity or the treatment (routine administration of high antipsychotic doses).
  
  
  
  We followed up our original investigation using a new group of 137 patients with acute schizophrenia and 45 healthy subjects, and then pooled the two cohorts to conduct the following analysis on a total of 274 patients. The associations of serum pentosidine and pyridoxal levels with duration of education, estimated duration of medication, the severity of symptoms, and daily doses of antipsychotics, antiparkinsonian drugs, and anxiolytics were evaluated by multiple linear regression analysis.
  
  
  
  The combined cohort of 274 patients exhibited abnormally high serum levels of pentosidine, were associated with a higher daily dose of antipsychotic drugs and a longer estimated duration of medication without statistical significance of diagnosis. This was also observed in the patients treated with antipsychotic polypharmacy, but the serum pentosidine levels of patients treated with first- or second-generation antipsychotic monotherapy showed no relationship with these two variables.
  
  
  
  High levels of serum pentosidine were associated with high daily doses of antipsychotic drugs and a longer estimated duration of medication in patients treated with antipsychotic polypharmacy.
authors.affiliation: Juntendo University Schizophrenia Projects (JUSP), Department of Psychiatry, Juntendo University, Faculty of Medicine, Tokyo, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Sannohe
authors.affiliation: Juntendo University Schizophrenia Projects (JUSP), Department of Psychiatry, Juntendo University, Faculty of Medicine, Tokyo, Japan. Electronic address: otoru@juntendo.ac.jp.
authors.forename: Tohru
authors.initials: T
authors.lastname: Ohnuma
authors.affiliation: Department of Advanced Medicine, Medical Research Institute,Kanazawa Medical University, Ishikawa, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Takeuchi
authors.affiliation: Juntendo University Schizophrenia Projects (JUSP), Department of Psychiatry, Juntendo University, Faculty of Medicine, Tokyo, Japan.
authors.forename: Eriko
authors.initials: E
authors.lastname: Tani
authors.affiliation: Juntendo University Schizophrenia Projects (JUSP), Department of Psychiatry, Juntendo University, Faculty of Medicine, Tokyo, Japan.
authors.forename: Yasue
authors.initials: Y
authors.lastname: Miki
authors.affiliation: Juntendo University Schizophrenia Projects (JUSP), Department of Psychiatry, Juntendo University, Faculty of Medicine, Tokyo, Japan.
authors.forename: Mayu
authors.initials: M
authors.lastname: Takeda
authors.affiliation: Juntendo University Schizophrenia Projects (JUSP), Department of Psychiatry, Juntendo University, Faculty of Medicine, Tokyo, Japan.
authors.forename: Narimasa
authors.initials: N
authors.lastname: Katsuta
authors.affiliation: Juntendo University Schizophrenia Projects (JUSP), Department of Psychiatry, Juntendo University, Faculty of Medicine, Tokyo, Japan.
authors.forename: Yuto
authors.initials: Y
authors.lastname: Takebayashi
authors.affiliation: Juntendo University Schizophrenia Projects (JUSP), Department of Psychiatry, Juntendo University, Faculty of Medicine, Tokyo, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Juntendo University Schizophrenia Projects (JUSP), Department of Psychiatry, Juntendo University, Faculty of Medicine, Tokyo, Japan.
authors.forename: Shohei
authors.initials: S
authors.lastname: Nishimon
authors.affiliation: Juntendo University Schizophrenia Projects (JUSP), Department of Psychiatry, Juntendo University, Faculty of Medicine, Tokyo, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Kimoto
authors.affiliation: Juntendo University Schizophrenia Projects (JUSP), Department of Psychiatry, Juntendo University, Faculty of Medicine, Tokyo, Japan.
authors.forename: Ryoko
authors.initials: R
authors.lastname: Higashiyama
authors.affiliation: Juntendo University Schizophrenia Projects (JUSP), Department of Psychiatry, Juntendo University, Faculty of Medicine, Tokyo, Japan.
authors.forename: Nobuto
authors.initials: N
authors.lastname: Shibata
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Juntendo University, Faculty of Medicine, Tokyo, Japan.
authors.forename: Tomohito
authors.initials: T
authors.lastname: Gohda
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Juntendo University, Faculty of Medicine, Tokyo, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Sho-Ichi
authors.initials: SI
authors.lastname: Yamagishi
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Juntendo University, Faculty of Medicine, Tokyo, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tomino
authors.affiliation: Juntendo University Schizophrenia Projects (JUSP), Department of Psychiatry, Juntendo University, Faculty of Medicine, Tokyo, Japan.
authors.forename: Heii
authors.initials: H
authors.lastname: Arai
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008239:Lysine / Q000031:analogs & derivatives* / Q000097:blood; D008297:Male; D008875:Middle Aged; D019338:Polypharmacy; D012559:Schizophrenia / Q000097:blood* / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D001120:Arginine; C062187:pentosidine; D008239:Lysine
keywords: Antipsychotics; Dose; Pentosidine; Polypharmacy; Schizophrenia