Takeuchi, Hiroyoshi

写真a

Affiliation

School of Medicine, Department of Neuropsychiatry （Shinanomachi）

Position

Associate Professor
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Research Areas 【 Display / hide 】

  • Life Science / Psychiatry

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Research Keywords 【 Display / hide 】

  • Antipsychotics

  • Schizophrenia

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Papers 【 Display / hide 】

  • Association between subjective distress and symptom domains in patients with treatment-resistant schizophrenia receiving clozapine.

    Tsukahara M, So R, Nomura N, Kitagawa K, Mizuno Y, Misawa F, Kodama M, Uchida H, Mimura M, Takeuchi H

    Schizophrenia research （Schizophrenia Research)  240   228 - 230 2022.01

    ISSN  0920-9964

  • Correction: An International Adult Guideline for Making Clozapine Titration Safer by Using Six Ancestry-Based Personalized Dosing Titrations, CRP, and Clozapine Levels.

    de Leon J, Schoretsanitis G, Smith RL, Molden E, Solismaa A, Seppälä N, Kopeček M, Švancer P, Olmos I, Ricciardi C, Iglesias-Garcia C, Iglesias-Alonso A, Spina E, Ruan CJ, Wang CY, Wang G, Tang YL, Lin SK, Lane HY, Kim YS, Kim SH, Rajkumar AP, González-Esquivel DF, Jung-Cook H, Baptista T, Rohde C, Nielsen J, Verdoux H, Quiles C, Sanz EJ, De Las Cuevas C, Cohen D, Schulte PFJ, Ertuğrul A, Anıl Yağcıoğlu AE, Chopra N, McCollum B, Shelton C, Cotes RO, Kaithi AR, Kane JM, Farooq S, Ng CH, Bilbily J, Hiemke C, López-Jaramillo C, McGrane I, Lana F, Eap CB, Arrojo-Romero M, Rădulescu FŞ, Seifritz E, Every-Palmer S, Bousman CA, Bebawi E, Bhattacharya R, Kelly DL, Otsuka Y, Lazary J, Torres R, Yecora A, Motuca M, Chan SKW, Zolezzi M, Ouanes S, De Berardis D, Grover S, Procyshyn RM, Adebayo RA, Kirilochev OO, Soloviev A, Fountoulakis KN, Wilkowska A, Cubała WJ, Ayub M, Silva A, Bonelli RM, Villagrán-Moreno JM, Crespo-Facorro B, Temmingh H, Decloedt E, Pedro MR, Takeuchi H, Tsukahara M, Gründer G, Sagud M, Celofiga A, Ignjatovic Ristic D, Ortiz BB, Elkis H, Pacheco Palha AJ, LLerena A, Fernandez-Egea E, Siskind D, Weizman A, Masmoudi R, Mohd Saffian S, Leung JG, Buckley PF, Marder SR, Citrome L, Freudenreich O, Correll CU, Müller DJ

    Pharmacopsychiatry  2022.01

    ISSN  0176-3679

  • Combination Therapy of Long-Acting Injectable Second-Generation Antipsychotics and Oral Antipsychotics: A Retrospective Chart Review and Prescribers' Attitude Survey.

    Misawa F, Amemiya A, Fujii Y, Takeuchi H

    Journal of clinical psychopharmacology （Journal of Clinical Psychopharmacology)  42 （ 1 ） 81 - 86 2022.01

    ISSN  0271-0749

    　View Summary

    Background: Although long-acting injectable antipsychotics (LAI-APs) have been considered as a monotherapeutic option in the maintenance treatment of schizophrenia, it has been recently reported that the combination therapy of LAI-APs and oral antipsychotics (OAPs) is common. Methods: We conducted a retrospective chart review to examine the situation of the combination therapy of LAI second-generation antipsychotics (LAI-SGAs) and OAPs, and a questionnaire survey to investigate prescribers' attitudes toward the combination therapy. We included patients who received any LAI-SGAs for 1 month or longer and classified them into monotherapy and combination therapy groups. We collected information on age, sex, primary psychiatric diagnosis, and concomitant psychotropic medications. Results: Of the 132 patients, 39 (29.5%) received the combination therapy of LAI-SGAs and OAPs. Long-acting injectable risperidone was significantly associated with receiving the combination therapy compared with LAI aripiprazole. Olanzapine was the most common OAP in combination with LAI-SGAs. Only 8 patients (20.5%) concurrently received the same type of OAPs as LAI-SGAs. More than 60% of the patients received OAP polypharmacy before the initiation of LAI-SGAs. The psychiatrists in charge prescribed LAI-SGAs mainly because of a concern about adherence, and OAPs mainly because of insufficient dose of LAI-SGAs, to patients in the combination therapy group. They estimated that adherence to OAPs in two thirds of the patients in the combination therapy group was 80% or higher. Conclusions: The present study showed that the combination therapy of LAI-SGAs and OAPs is often conducted in real-world clinical practice. Considering the reason for the introduction of LAI-APs, clinicians should carefully monitor patients' adherence to OAPs concurrently used with LAI-APs.

  • An International Adult Guideline for Making Clozapine Titration Safer by Using Six Ancestry-Based Personalized Dosing Titrations, CRP, and Clozapine Levels.

    de Leon J, Schoretsanitis G, Smith RL, Molden E, Solismaa A, Seppälä N, Kopeček M, Švancer P, Olmos I, Ricciardi C, Iglesias-Garcia C, Iglesias-Alonso A, Spina E, Ruan CJ, Wang CY, Wang G, Tang YL, Lin SK, Lane HY, Kim YS, Kim SH, Rajkumar AP, González-Esquivel DF, Jung-Cook H, Baptista T, Rohde C, Nielsen J, Verdoux H, Quiles C, Sanz EJ, De Las Cuevas C, Cohen D, Schulte PFJ, Ertuğrul A, Anıl Yağcıoğlu AE, Chopra N, McCollum B, Shelton C, Cotes RO, Kaithi AR, Kane JM, Farooq S, Ng CH, Bilbily J, Hiemke C, López-Jaramillo C, McGrane I, Lana F, Eap CB, Arrojo-Romero M, Rădulescu FŞ, Seifritz E, Every-Palmer S, Bousman CA, Bebawi E, Bhattacharya R, Kelly DL, Otsuka Y, Lazary J, Torres R, Yecora A, Motuca M, Chan SKW, Zolezzi M, Ouanes S, De Berardis D, Grover S, Procyshyn RM, Adebayo RA, Kirilochev OO, Soloviev A, Fountoulakis KN, Wilkowska A, Cubała WJ, Ayub M, Silva A, Bonelli RM, Villagrán-Moreno JM, Crespo-Facorro B, Temmingh H, Decloedt E, Pedro MR, Takeuchi H, Tsukahara M, Gründer G, Sagud M, Celofiga A, Ignjatovic Ristic D, Ortiz BB, Elkis H, Pacheco Palha AJ, LLerena A, Fernandez-Egea E, Siskind D, Weizman A, Masmoudi R, Mohd Saffian S, Leung JG, Buckley PF, Marder SR, Citrome L, Freudenreich O, Correll CU, Müller DJ

    Pharmacopsychiatry （Pharmacopsychiatry)   2021.12

    ISSN  0176-3679

    　View Summary

    This international guideline proposes improving clozapine package inserts worldwide by using ancestry-based dosing and titration. Adverse drug reaction (ADR) databases suggest that clozapine is the third most toxic drug in the United States (US), and it produces four times higher worldwide pneumonia mortality than that by agranulocytosis or myocarditis. For trough steady-state clozapine serum concentrations, the therapeutic reference range is narrow, from 350 to 600 ng/mL with the potential for toxicity and ADRs as concentrations increase. Clozapine is mainly metabolized by CYP1A2 (female non-smokers, the lowest dose; male smokers, the highest dose). Poor metabolizer status through phenotypic conversion is associated with co-prescription of inhibitors (including oral contraceptives and valproate), obesity, or inflammation with C-reactive protein (CRP) elevations. The Asian population (Pakistan to Japan) or the Americas' original inhabitants have lower CYP1A2 activity and require lower clozapine doses to reach concentrations of 350 ng/mL. In the US, daily doses of 300-600 mg/day are recommended. Slow personalized titration may prevent early ADRs (including syncope, myocarditis, and pneumonia). This guideline defines six personalized titration schedules for inpatients: 1) ancestry from Asia or the original people from the Americas with lower metabolism (obesity or valproate) needing minimum therapeutic dosages of 75-150 mg/day, 2) ancestry from Asia or the original people from the Americas with average metabolism needing 175-300 mg/day, 3) European/Western Asian ancestry with lower metabolism (obesity or valproate) needing 100-200 mg/day, 4) European/Western Asian ancestry with average metabolism needing 250-400 mg/day, 5) in the US with ancestries other than from Asia or the original people from the Americas with lower clozapine metabolism (obesity or valproate) needing 150-300 mg/day, and 6) in the US with ancestries other than from Asia or the original people from the Americas with average clozapine metabolism needing 300-600 mg/day. Baseline and weekly CRP monitoring for at least four weeks is required to identify any inflammation, including inflammation secondary to clozapine rapid titration.

  • Clozapine Once-Daily Versus Divided Dosing Regimen: A Cross-sectional Study in Japan.

    Kitagawa K, So R, Nomura N, Tsukahara M, Misawa F, Kodama M, Uchida H, Bies R, Straubinger T, Banker C, Mizuno Y, Mimura M, Takeuchi H

    Journal of clinical psychopharmacology  2021.12

    ISSN  0271-0749

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Papers, etc., Registered in KOARA 【 Display / hide 】

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Reviews, Commentaries, etc. 【 Display / hide 】

  • せん妄に対する抗うつ薬・抗ヒスタミン薬の使用実態とその効果　後方視的診療録調査

    河野 佐代子, 井出 健太郎, 児玉 啓輔, 竹内 啓善

    総合病院精神医学 ((一社)日本総合病院精神医学会)  33 ( Suppl. ) S - 156 2021.11

    ISSN  0915-5872

  • 【今日の精神科治療ハンドブック】(第2章)統合失調症または他の一次性精神症群　統合失調感情症

    下村 雄太郎, 竹内 啓善

    精神科治療学 ((株)星和書店)  36 ( 増刊 ) 36 - 37 2021.10

    ISSN  0912-1862

  • 【抗精神病薬持効性注射剤をめぐって】抗精神病薬持効性注射剤による副作用とその対応

    児玉 啓輔, 三澤 史斉, 竹内 啓善

    臨床精神医学 ((株)アークメディア)  50 ( 10 ) 1049 - 1055 2021.10

    ISSN  0300-032X

  • 精神医学における研究方法の特徴を改めて考える〜身体医学との異同に注目して〜　評価における壁　当事者と臨床家における評価の相違

    竹内 啓善

    精神神経学雑誌 ((公社)日本精神神経学会)   ( 2021特別号 ) S371 - S371 2021.09

    ISSN  0033-2658

  • 【向精神薬の出口戦略】向精神薬の出口戦略　抗精神病薬

    稲田 健, 金沢 徹文, 岸本 泰士郎, 竹内 啓善, 嶽北 佳輝, 谷 英明, 樽谷 精一郎, 徳増 卓宏, 橋本 直樹, 松井 健太郎, 山田 浩樹

    臨床精神薬理 ((株)星和書店)  24 ( 9 ) 919 - 927 2021.09

    ISSN  1343-3474

    　View Summary

    統合失調症の治療は生物学的治療と心理社会療法が組み合わせて行われるが、維持期統合失調症の薬物療法においては、抗精神病薬の服薬継続が推奨されている。したがって、抗精神病薬による薬物療法の出口戦略としては、薬物療法を減量あるいは整理しつつも、継続し、再発を防ぎ、リハビリテーションを円滑に進め、リカバリーを達成することにあると考えられる。そのために、抗精神病薬を減量あるいは単剤化するという2つの戦略が考えられ、それぞれについてのシステマティックレビュー、ガイドライン作成、デシジョンエイド作成がなされた。減量することと単剤化しないことを弱く推奨するガイドラインとなったが、患者背景を注意深く検討し、共同意思決定することが重要である。(著者抄録)

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Presentations 【 Display / hide 】

  • Antipsychotic treatment algorithm for first episode schizophrenia - a guide for clinicians

    Agid, Ofer, Fervaha, Gagan, Zipursky, Robert, Takeuchi, Hiroyoshi, Gorge, Foussias, Shireen, Huma, Remington, Gary

    EARLY INTERVENTION IN PSYCHIATRY, 

    2016.10

  • Depressive Symptoms and Progressive Hippocampal Volume Atrophy Accelerates the Conversion Process to Dementia from Mild Cognitive Impairment

    Chung, Jun Ku, Caravaggio, Fernando, Chakravarty, Mallar, Gerretsen, Philip, Graff-Guerrero, Ariel, Iwata, Yusuke, Mulsant, Benoit, Nakajima, Shinichiro, Patel, Raihaan, Plitman, Eric, Takeuchi, Hiroyoshi

    INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY, 

    2016.06

  • Synergic Effect of Depressive Symptoms and Small Hippocampal Volume Accelerates the Conversion Process to Dementia from Mild Cognitive Impairment

    Chung, Jun Ku, Plitman, Eric, Nakajima, Shinichiro, Chakravarty, Mallar, Caravaggio, Fernando, Takeuchi, Hiroyoshi, Gerretsen, Philip, Iwata, Yusuke, Patel, Raihaan, Mulsant, Benoit, Graff-Guerrero, Ariel

    BIOLOGICAL PSYCHIATRY, 

    2016.05

  • Estimated dopamine D2 receptor occupancy from plasma concentrations of atypical antipsychotics and subjective experience/drug attitude in schizophrenia: An analysis of the CATIE data (vol 150, pg 373, 2013)

    Takeuchi, Hiroyoshi, Suzuki, Takefumi, Bies, Robert R., Remington, Gary, Mamo, David C., Pollock, Bruce G., MasaruMimura, Uchida, Hiroyuki

    SCHIZOPHRENIA RESEARCH, 

    2015.03

  • 非定型抗精神病薬の普及度と適応に関する研究

    Tomita Masayuki, Watanabe Kouichirou, Kikuchi Toshiaki, Takeuchi Hiroyoshi, Kishimoto Taishirou, Nomura Kensuke, Nakagawa Atsuo, Yamazawa Ryouko, Uchida Hiroyuki, Suzuki Takefumi, Nozaki Shouko, Tomita Atsuko, Takano Harumasa, Inagaki Ataru, Yagi Gouhei

    第12回日本臨床精神神経薬理学会, 

    2002.10
    , 

    Poster presentation

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Research Projects of Competitive Funds, etc. 【 Display / hide 】

  • Aripiprazole dose reduction in stable schizophrenia

    2023.04
    -
    2026.03

    基盤研究(C), Principal investigator

  • 投与回数とゲノム薬理学による統合失調症の抗精神病薬アドヒアランス向上戦略

    2018.04
    -
    2021.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Early-Career Scientists , Principal investigator

    　View Summary

    本研究は3ヶ年計画であり、抗精神病薬を1日複数回服用している統合失調患者を対象とし、1日1回投与に変更することで服薬事象監視システム（もしくは自動服薬記録薬瓶）（MEMS）によって測定した服薬アドヒアランスが向上するかについて、無作為化比較試験（RCT）によって検証するものである。同時に、薬物動態学・薬力学関連分子の遺伝子多型を調べ、どのような患者が1日1回投与に適しているかについても明らかにする。研究次年度である昨年度は、複数の評価者を雇用し評価体制を構築した。その上で、研究対象者の登録を行い、現時点で6名登録され、2名が脱落、4名が完遂している。
    加えて、本研究の背景に寄与することから、向精神薬の1日1回投与と分割投与を比較したRCTのメタアナリシスを行った。1日1回投与は、分割投与と比較し、有効性および効果おいて有意な差がなかったが、有害事象のうち眠気、不安について有意に少なかった。向精神薬はその種類や半減期にかかわらず1日1回投与で十分であることを示し、査読あり英文学術誌に受理された（Kikuchi Y, Shimomura Y, Suzuki T, Uchida H, Mimura M, Takeuchi H. Journal of Clinical Psychiatry. In press）。これらの結果は、本研究の仮説の一部を支持するものである。
    基準を満たす研究対象者が当初の計画より少なく、また新型コロナウイルスの影響により、研究対象者の登録が遅れている。
    研究協力施設を増やし、緊密に連携をとりながら、積極的に研究対象者の登録を推進していく予定である。

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Courses Taught 【 Display / hide 】

  • TREATMENT OF PSYCHIATRIC DISORDERS

    2024

  • PHARMACOECONOMICS

    2024

  • LECTURE SERIES, PSYCHIATRY

    2024

  • CLINICAL CLERKSHIP IN PSYCHIATRY

    2024

  • LECTURE SERIES, PSYCHIATRY

    2023

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