Mishima Kazuo

写真a

Affiliation

Graduate School of Medicine  Doctorial Course in Medicine  Bioregulatory Medicine  Department of Neuropsychiatry

Research Interests 【 display / non-display

  • Sleep medicine

  • 精神神経科学/時間生物学/分子遺伝学/睡眠/加齢変化/精神薬理学的研究

  • Psychiatry

  • Chronobiology

  • 精神科学

Graduating School 【 display / non-display

  •  
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    1987.03

    Akita University   Faculty of Medicine   Graduated

Campus Career 【 display / non-display

  • 2018.09
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    Now

    Akita University   Graduate School of Medicine   Doctorial Course in Medicine   Bioregulatory Medicine   Professor  

Research Areas 【 display / non-display

  • Life Science / Psychiatry

  • Life Science / Neuroscience-general

  • Life Science / Neuroscience-general

 

Research Achievements 【 display / non-display

    ◆Original paper【 display / non-display

  • Efficacy and safety of insomnia treatment with lemborexant in older adults: analyses from three clinical trials.

    Mark H Gotfried, Sanford H Auerbach, Thien Thanh Dang-Vu, Kazuo Mishima, Dinesh Kumar, Margaret Moline, Manoj Malhotra

    Drugs & aging     2024.08  [Refereed]

    Research paper (journal)   International Co-author

    BACKGROUND: Insomnia is more common as people age. Several common hypnotics used to treat insomnia often do not adequately alleviate sleep issues in older adults and may be associated with negative residual effects such as an increased risk of falls, cognitive impairment, automobile accidents, and lack of response to auditory stimuli. The objective of these analyses of three clinical studies was to investigate the efficacy and safety of the dual orexin-receptor antagonist lemborexant (LEM) in older adults. METHODS: Study E2006-G000-304 (Study 304; NCT02783729) was a randomized, double-blind, placebo (PBO)-controlled, active-comparator trial where subjects with insomnia disorder received LEM 5 mg (LEM5), LEM 10 mg (LEM10), zolpidem tartrate extended-release 6.25 mg (ZOL), or PBO for 30 days. In crossover Study E2006-E044-106 (Study 106; NCT02583451), healthy subjects (good sleepers) received LEM 2.5 mg, LEM5, LEM10, or PBO for eight nights or zopiclone on days 1 and 8 (and PBO on days 2-7). In crossover Study E2006-A001-108 (Study 108; NCT03008447), healthy subjects received a single dose of LEM5, LEM10, PBO, or ZOL. Sleep assessments included polysomnography-based latency to persistent sleep (LPS), wake after sleep onset (WASO), WASO in the second half of the night (WASO2H), sleep efficiency, postural stability, middle-of-the-night and next-day cognitive performance, middle-of-the-night auditory awakening threshold and return-to-sleep latency, and driving performance. RESULTS: Overall, 453 of 1006 (45%; Study 304), 24 of 48 (50%; Study 106), and 28 of 56 (50%; Study 108) subjects were aged ≥ 65 years. In Study 304, LEM decreased (improved) LPS, WASO, and WASO2H from baseline more than ZOL and PBO; subjects treated with LEM had greater increases in sleep efficiency (improved) than with ZOL or PBO. In both Studies 304 and 108, postural stability was not impaired at waketime in subjects who received LEM compared with PBO. At waketime, LEM did not impair memory compared with PBO. In Study 108, following middle-of-the-night awakening, LEM and ZOL did not affect subjects' ability to awaken to auditory stimuli; LEM did not affect tests of memory and attention. In Study 106, LEM did not impair next-day driving performance in healthy elderly compared with PBO. LEM was well tolerated in subjects aged ≥ 65 years. CONCLUSIONS: LEM provided benefits on sleep variables without next-morning residual effects in subjects aged ≥ 65 years, supporting LEM as a treatment option for older adults with insomnia. TRIAL REGISTRATION NUMBERS AND DATES OF REGISTRATION: Study 304: ClinicalTrials.gov identifier, NCT02783729, date of registration, 26 May 2016. Study 106: ClinicalTrials.gov identifier, NCT02583451, date of registration, 22 October 2015. Study 108: ClinicalTrials.gov identifier, NCT03008447, date of registration, 2 January 2017.

    DOI PubMed

  • Pharmacokinetics, safety, and efficacy of daridorexant in Japanese subjects: Results from phase 1 and 2 studies.

    Makoto Uchiyama, Kazuo Mishima, Tomoko Yagi, Tatsuya Yoshihara, Takashi Eto, Clemens Muehlan, Osamu Togo, Yuichi Inoue

    Journal of sleep research     e14302   2024.08  [Refereed]

    Research paper (journal)   Domestic Co-author

    Daridorexant is a dual orexin receptor antagonist for the treatment of insomnia. We report results from the first two randomised, double-blind clinical studies of daridorexant in Japanese subjects. In the Phase 1 study, daridorexant (10, 25, 50 mg) or placebo were administered in the morning for 4 days in 24 young (mean age 26.9 years) and 24 older (mean age 69.7 years) healthy Japanese adults. Daridorexant reached a peak plasma concentration within 1.0 h across every dose and age group. For all doses, the mean plasma concentration of daridorexant showed a similar change between the age groups. Exposure parameters increased dose-dependently with minimal/no accumulation upon repeated dosing. The terminal half-life was ~8 h. In the Phase 2, four-period, four-way crossover study, 47 Japanese subjects (mean age 50.4 years) with insomnia disorder were randomised to receive four treatments (daridorexant 10, 25, 50 mg, placebo) during four treatment periods, each consisting of two treatment nights (5-12 day washout between treatment periods). Subjects continued their fourth treatment for 12 further days. A statistically significant dose-response relationship (multiple-comparison procedure-modelling, p < 0.0001) was found in the reduction of polysomnography-measured wake after sleep onset (WASO; primary endpoint) and latency to persistent sleep (secondary endpoint) from baseline to days 1/2. Statistically significant dose-response relationships were also observed for secondary subjective endpoints from baseline to days 1/2 (sWASO, latency to sleep onset). All daridorexant doses were well tolerated, with no treatment discontinuations and no next-morning residual effects. These results supported further investigation of daridorexant in Japanese patients with insomnia disorder.

    DOI PubMed

  • Evaluation of prescribing patterns of switching to and add-on lemborexant in patients treated with hypnotic medication: a nationwide claims database study in Japan.

    Sachiko Tanaka-Mizuno, Kenichi Fujimoto, Kazuo Mishima, Yukinori Sakata, Toshiki Fukasawa, Kayoko Mizuno, Satomi Yoshida, Mika Ishii, Takehiro Taninaga, Naoki Kubota, Margaret Moline, Koji Kawakami

    Expert opinion on pharmacotherapy     2024.08  [Refereed]

    Research paper (journal)   Domestic Co-author

    BACKGROUND: When considering changing hypnotic pharmacotherapy, lemborexant has attracted attention as a candidate due to its effectiveness and safety profile. However, few studies have investigated switching patterns in clinical practice. RESEARCH DESIGN AND METHODS: We conducted a retrospective cohort study using a nationwide claims database. Patients prescribed a single hypnotic who either subsequently switched to (switching cohort) or were additionally prescribed (add-on cohort) lemborexant between July 2020 and December 2021 were identified. Proportion of successful switching was defined as remaining on lemborexant alone or without any hypnotic at six months after lemborexant initiation. RESULTS: Success proportion was 70.1% in the switching cohort (n = 4,861) and 38.6% in the add-on cohort (n = 9,423). In the add-on cohort, success proportion was lower in patients with a hypnotic history of ≥180 days (31.4%) and in patients whose prescribed hypnotic was a benzodiazepine or non-benzodiazepine (31.5% and 37.6%, respectively). CONCLUSION: Proportion of successful switching was higher in patients who switched to lemborexant than in those who added lemborexant as a concomitant treatment. The lower success proportion in the add-on cohort might be related to clinically more severe insomnia, and/or a concomitant prescription of a benzodiazepine or non-benzodiazepine, from which discontinuation may be challenging.

    DOI PubMed

  • Successful Electroconvulsive Therapy for Tardive Dyskinesia and Tardive Dystonia Refractory to Valbenazine Treatment: A Case Report and Narrative Literature Review

    Keisuke Irinaka, Yu Itoh, Kazuhisa Yoshizawa, Masaya Ogasawara, Naoko Ayabe, Kazuo Mishima, Masahiro Takeshima

    Clinical Psychopharmacology and Neuroscience     2024.08  [Refereed]

    Research paper (journal)   Domestic Co-author

    DOI

  • Association between benzodiazepine anxiolytic polypharmacy and concomitant psychotropic medications in Japan: a retrospective cross-sectional study.

    Masahiro Takeshima, Kazuhisa Yoshizawa, Masaya Ogasawara, Mizuki Kudo, Yu Itoh, Naoko Ayabe, Nana Shibata, Kazuo Mishima

    Frontiers in psychiatry   15   1405049 - 1405049   2024.07  [Refereed]

    Research paper (journal)   Domestic Co-author

    INTRODUCTION: Guidelines for various psychiatric disorders recommend short-term use of benzodiazepine anxiolytic monotherapy in few cases. Contrarily, benzodiazepine anxiolytic polypharmacy (BAP) is not recommended in any case. However, BAP is often used in real world. Therefore, this study aimed to determine the association between BAP and concomitant use of psychotropic medications. METHOD: This retrospective cross-sectional study used claims data from the Japan Medical Data Center. Medical information of health insurance subscribers treated with benzodiazepine anxiolytics in June 2019 was extracted. Prescription of two or more benzodiazepine anxiolytics was defined as BAP. Binary logistic regression analysis was performed to investigate the factors associated with BAP, using age group, sex, type of subscriber, and number of concomitant hypnotics, antidepressants, and antipsychotics (none, one, and two or more) as covariates. RESULT: The eligible participants were 104,796 adults who were prescribed benzodiazepine anxiolytics. Among them, 12.6% were prescribed two or more drugs. Logistic regression analysis revealed that BAP was significantly associated with those who received hypnotic monotherapy (adjusted odds ratio [aOR]: 1.04, 95% confidence interval [CI]: 1.001-1.09, p=0.04), antidepressant monotherapy and polypharmacy (aOR: 1.57, 95% CI: 1.51-1.63, p<0.001 and aOR: 1.98, 95% CI: 1.88-2.09, p<0.001, respectively), and antipsychotic monotherapy and polypharmacy (aOR: 1.12, 95% CI: 1.07-1.19, p<0.001 and aOR: 1.41, 95% CI: 1.30-1.54, p<0.001, respectively). Conversely, lower BAP was associated with those who received hypnotic polypharmacy (aOR: 0.86, 95% CI: 0.81-0.91, p<0.001). DISCUSSION: This study showed that the greater the number of concomitant antidepressants and antipsychotics, the greater the association with BAP. Since combination therapy with antidepressants or antipsychotics is generally not recommended, patients receiving combination therapy with these medications may be resistant to pharmacotherapy. Therefore, implementing the recommended non-pharmacological treatments may reduce BAP.

    DOI PubMed

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    ◆Introduction and explanation【 display / non-display

  • Autoimmune Encephalitis in Psychiatry

    筒井幸, 筒井幸, 筒井幸, 大森佑貴, 神林崇, 神林崇, 加藤倫紀, 嵯峨佑史, 三島和夫, 清水徹男, 加藤征夫, 田中惠子

    精神神経学雑誌   126 ( 2 )   2024.02

    Introduction and explanation (scientific journal)   Domestic Co-author

    J-GLOBAL

  • Efficacy and safety of lithium and lamotrigine for the bipolar disorder in the maintenance phase: A systematic review and meta-analysis.

    岸太郎, 江角悟, 大矢一登, 奥谷理, 佐久間健二, 野村郁雄, 橋本保彦, 波多野正和, 波多野正和, 松井佑樹, 松田勇紀, 三宅誕実, 三島和夫, 岩田仲生

    臨床精神薬理   24 ( 9 ) 937 - 942   2021

    Introduction and explanation (scientific journal)   Domestic Co-author

    J-GLOBAL

  • How to use, reduce, and stop hypnotics after insomnia remission

      22 ( 8 ) 815 - 820   2019.08

    Introduction and explanation (scientific journal)  

  • Non-visual Effects of Light : Influence on alertness and cognitive function

      61 ( 8 ) 883 - 889   2019.08

    Introduction and explanation (scientific journal)  

  • 【知っておきたい器質性・症状性・薬剤性の精神障害:Update】抗NMDA受容体脳炎

    筒井 幸, 馬越 秋瀬, 神林 崇, 田中 惠子, 清水 徹男, 三島 和夫

    臨床精神医学 ( (株)アークメディア )  48 ( 1 ) 11 - 16   2019.01

    Introduction and explanation (scientific journal)  

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    ◆Other【 display / non-display

  • Association of stay-home order during COVID-19 pandemic with depressive symptoms and suicide-related ideation in university students in Japan

    野村恭子, 南園佐知子, 前田恵理, KIM Roseline, 岩田豊人, 平山純子, 尾野恭一, 伏見雅人, 後藤猛, 三島和夫, 山本文雄

    日本心身医学会総会ならびに学術講演会抄録集   62nd (CD-ROM)   2021

    Summary of the papers read (national conference and other science council)   Domestic Co-author

    J-GLOBAL

  • 睡眠・覚醒相後退障害に対する心理社会支援プログラム開発の試み

    綾部直子, 吉村道孝, 栗山健一, 三島和夫, 三島和夫

    日本睡眠環境学会学術大会抄録集   28th   106   2019.09

    Summary of the papers read (national conference and other science council)  

    J-GLOBAL

  • 精神科学と神経免疫学のクロストーク 精神科領域からみた自己免疫性辺縁系脳炎

    筒井 幸, 馬越 秋瀬, 奥口 悠紀, 神林 崇, 田中 惠子, 清水 徹男, 三島 和夫

    精神神経学雑誌 ( (公社)日本精神神経学会 )  ( 2019特別号 ) S340 - S340   2019.06

    Summary of the papers read (national conference and other science council)  

  • 向精神薬の処方がもたらす転倒骨折リスクに関する薬剤疫学調査

    北村真吾, 榎本みのり, 三井寺浩幸, 立森久照, 三島和夫

    国立精神・神経医療研究センター精神保健研究所年報   ( 30 ) 235   2017.10

    Summary of the papers read (national conference and other science council)  

    J-GLOBAL

  • 多施設共同RCTによる不眠症に対する認知行動療法(Cognitive Behavioral Therapy for Insomnia:CBT‐I)の有効性

    綾部直子, 鈴木みのり, 立森久照, 北村真吾, 亀井雄一, 三島和夫

    国立精神・神経医療研究センター精神保健研究所年報   ( 30 ) 235   2017.10

    Summary of the papers read (national conference and other science council)  

    J-GLOBAL

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Books 【 display / non-display

  • Tasman’s Psychiatry

    三島和夫

    Springer  2023.01

Grant-in-Aid for Scientific Research 【 display / non-display

  • Grant-in-Aid for Scientific Research(B)

    Project Year: 2023.04  -  2027.03 

  • Construction and feature analysis of a model for predicting clinical outcomes of psychiatric disorders using sleep, behavioral, and physiological parameters.

    Grant-in-Aid for Scientific Research(B)

    Project Year: 2022.04  -  2025.03 

  • Grant-in-Aid for Scientific Research(B)

    Project Year: 2019.04  -  2022.03 

  • Grant-in-Aid for Scientific Research(B)

    Project Year: 2016.04  -  2019.03 

  • Grant-in-Aid for Scientific Research(S)

    Project Year: 2015.04  -  2016.03 

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Presentations 【 display / non-display

  • Effects of Japanese policies and novel hypnotics on long-term prescriptions of hypnotics

    Masahiro Takeshima, Kazuhisa Yoshizawa, Masaya Ogasawara, Yu Itoh, Kazuo Mishima

    35th WORLD CONGRESS World Congress Collegium Internationale Neuro-Psychopharmacologicum  (Tokyo)  2024.05  -  2024.05 

  • Safety and Efficacy of Lemborexant in Patients with Insomnia Disorder: Report from a Post-marketing Observational Study

    Kazuo Mishima1 Kenichi Fujimoto, Akira Endo,Mika Ishi

    35th WORLD CONGRESS World Congress Collegium Internationale Neuro-Psychopharmacologicum  (Tokyo)  2024.05  -  2024.05 

 

Academic Activity 【 display / non-display

  • 2020.10
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