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The development of custom-made therapy of depression used genomic analysis concerned with the response of drug therapy

Research Project

Project/Area Number 13670991
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Psychiatric science
Research InstitutionNIIGATA UNIVERSITY

Principal Investigator

SOMEYA Toshiyuki  NIIGATA UNIVERSITY Graduate School of Medical and Dental Sciences, Professor, 大学院・医歯学総合研究科, 教授 (50187902)

Co-Investigator(Kenkyū-buntansha) MURATAKE Tatsuyuki  University Medical Hospital, Lecturer, 医学部附属病院, 講師 (60311669)
SHIOIRI Toshiki  Graduate School of Medical and Dental Sciences, Associate Professor, 大学院・医歯学総合研究科, 助教授 (40235487)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2002: ¥800,000 (Direct Cost: ¥800,000)
Keywordsdepression / SSRI / fluvoxamine / clinical effect / plasma concentration / CYP2D& / 5-HTTLPR
Research Abstract

Selective Serotonin-reuptake Inhibitor (SSRI) has been the first choice drug for the treatment of depression, but there are many people that should be select another drug, for example, tricyclic antidepressant (TCA). Though there were various trials underwent in the purpose of predict to antidepressant effect in the different view point, there was no established method that could be available in clinical use.
We investigated 58 patients being treated with fluvoxamine (FLV) for 12 weeks, and analyzed the correlation between clinical effect of FLV and characteristics of depression, characteristics of pharmacokinetics of FLV (cf. plasma levels of FLV), characteristics of pharmacodynamics of FLV (cf. 5-HTTLPR).
Result of our study, there was "enough plasma concentration" of FLV, we found that the prediction used by plasma level of FLV was more available than that used by FLV dosage. Further, we found that there are much individual differences in dosage established "enough plasma concentration" of FLV, and that CYP2D6 polymorphism and CYP1A2 activity induced by smoking might be useful for predicting this individual differences.
On the other hand, there is no significantly correlation between 5-HTTLPR and antidepressant effect of FLV.
It will be necessary in the future to conduct studies involving larger numbers of patients.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (35 results)

All Other

All Publications (35 results)

  • [Publications] Someya, T.: "Establishment of enzyme immuno-assay for measuring serum sultopride level"Ther Drug Monit. 23(3). 277-281 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Someya, T.: "A survey on the drug therapy for delirium"Psychiatry Clin Neurosci. 55(4). 397-402 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Suzuki, Y.: "Importance of the cytochrome P450 2D6 genotype for the drug metabolic interaction between chlorpromazine and haloperidol"Ther Drug Monit. 23(4). 363-368 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yokono, A.: "The impact of CYP2C19 and CYP2D6 genotypes on the metabolism of clomipramine in Japanese psychiatric patients"J Clin Psychopharmacol. 21(6). 549-555 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shimoda, K.: "Lack of impact of CYP1A2 genetic polymorphism (C/A polymorphism at position 734 in intron 1 and G/A polymorphism at position -2964 in the 5'-flanking region of CYP1A2) on the plasma concentration of haloperidol in smoking male Japanese with schizophrenia"Prog Neuropsychopharmacol Biol Psychiatry. 26(2). 261-265 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawashima, Y.: "Evaluation of dextromethorphan N-demethylation activity as a biomarker for cytochrome P4503A activity in man"Pharmacol Toxicol. 90(2). 82-88 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shimoda, K.: "Impact of CYP2C19 and CYP2D6 genotypes on metabolism of amitriptyline in Japanese psychiatric patients"J Clin Psychopharmacol. 22(4). 371-378 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Suzuki, Y.: "Effects of concomitant fluvoxamine on metabolism of alprazolam in Japanese psychiatric patients : Interaction with CYP2C19 mutated alleles"Eur J Clin Pharmacol. (In press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 染矢俊幸: "フルボキサミンの至適投与量を検証する-体内動態および遺伝子多型からの考察-"分子精神医学. 2(4). 64-72 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 遠藤太郎: "わが国における気分変調性障害の薬物療法の実際-「感情障害の薬物療法のガイドライン研究」に関するアンケート調査結果から-"臨床精神薬理. 6(1). 83-94 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 澤村一司: "Paroxetine血中濃度に及ぼす用量とCYP2D6遺伝子多型の影響"臨床精神薬理. 6(3). 331-335 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Someya, T.: "Establishment of enzyme immuno-assay for measuring serum sultopride level"Ther Drug Monit. 23(3). 277-281 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Someya, T.: "A survey on the drug therapy for delirium"Psychiatry Clin Neurosci. 55(4). 397-402 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Suzuki, Y.: "Importance of the cytochrome P450 2D6 genotype for the drug metabolic interaction between chlorpromazine and haloperidol"Ther Drug Monit. 23(4). 363-368 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yokono, A.: "The impact of CYP2C19 and CYP2D6 genotypes on the metabolism of clomipramine in Japanese psychiatric patients"J Clin Psychopharmacol. 21(6). 549-555 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shimoda, K.: "Lack of impact of CYP1A2 genetic polymorphism (C/A polymorphism at position 734 in intron 1 and G/A polymorphism at position -2964 in the 5'-flanking region of CYP1A2) on the plasma concentration of haloperidol in smoking male Japanese with schizophrenia"Prog Neuropsychopharmacol Biol Psychiatry. 26(2). 261-265 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawashima, Y.: "Evaluation of dextromethorphan N-demethylation activity as a biomarker for cytochrome P4503A activity in man"Pharmacol Toxicol. 90(2). 82-88 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shimoda, K.: "Impact of CYP2C19 and CYP2D6 genotypes on metabolism of amitriptyline in Japanese psychiatric patients"J Clin Psychopharmacol. 22(4). 371-378 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Suzuki, Y.: "Effects of concomitant fluvoxamine on metabolism of alprazolam in Japanese psychiatric patients : Interaction with CYP2C19 mutated alleles"Eur J Clin Pharmacol. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Someya, T.: "Fluvoxamine no sihtekiyouryou wo kensyousuru -tainaidoutai oyobi idennsitakei karano kousatsu-"Jpn J Molecular Psychiatry. 2(4). 64-72 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Endo, T.: "A survey on the pharmacotherapy of dysthymic disorder, in Japan"Jpn Clin Psychopharmacol. 6(1). 83-94 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sawamura, K.: "Effects of dosage and number of CYP2D6 mutated alleles on steady-state plasma concentration of paroxetine"Jpn Clin Psychopharmacol. 6(3). 331-335 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shimoda, K.: "Lack of impact of CYP1A2 genetic polymorphism (C/A polymorphism at position 734 in intron 1 and G/A polymorphism at position -2964 in the 5'-flanking region of CYP1A2) on the plasma concentration of haloperidol in smoking male Japanese with schizophrenia"Prog Neuropsychopharmacol Biol Psychiatry. 26(2). 261-265 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kawashima, Y.: "Evaluation of dextromethorphan N-demethylation activity as a biomarker for cytochrome P4503A activity in man"Pharmacol Toxicol. 90(2). 82-88 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Shimoda, K.: "The impact of CYP2C19 and CYP2D6 genotypes on the metabolism of amitriptyline in Japanese psychiatric patients"J Clin Psychopharmacol. 22(4). 371-378 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Suzuki, Y.: "Effects of concomitant fluvoxamine on metabolism of alprazolam in Japanese psychiatric patients : Interaction with CYP2C19 mutated alleles"Eur J Clin Pharmacol. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] 染矢俊幸: "フルボキサミンの至適投与量を検証する-体内動態および遺伝子多型からの考察-"分子精神医学. 2(4). 64-72 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 遠藤太郎: "わが国における気分変調性障害の薬物療法の実際-「環状障害の薬物療法のガイドライン研究」に関するアンケート調査結果から-"臨床精神薬理. 6(1). 83-94 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 澤村一司: "Paroxetine血中濃度に及ぼす用量とCYP2D6遺伝子多型の影響"臨床精神薬理. 6(3). 331-335 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Someya, T.: "Establishment of enzyme immuno-assay for measuring serum sultopride level"Ther Drug Monit. 23(3). 277-281 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Someya, T.: "A survey on the drug therapy for delirium"Psychiatry Clin Neurosci. 55(4). 397-402 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Suzuki, Y.: "Importance of the cytochrome P450 2D6 genotype for the drug metabolic interaction between chlorpromazine and haloperidol"Ther Drug Monit. 23(4). 363-368 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yokono, A.: "The impact of CYP2C19 and CYP2D6 genotypes on the metabolism of clomipramine in Japanese psychiatric patients"J Clin Psychopharmacol. 21(6). 549-555 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Shimoda, K.: "Lack of impact of CYP1A2 genetic polymorphism (C/A polymorphism at position 734 in intron 1 and G/A polymorphism at position -2964 in the 5'-flanking region of CYP1A2) on the plasma concentration of haloperidol in smoking male Japanese with schizophrenia"Prog Neuropsychopharmacol Biol Psychiatry. 26(2). 261-265 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kawashima, Y.: "Evaluation of dextromethorphan N-demethylation activity as a biomarker for cytochrome P4503A activity in man"Pharmacol Toxicol. (in press).

    • Related Report
      2001 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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