Development of the prevention of postoperative delirium based on the circadian rhythm stabilization in patients undergoing cardiovascular bypass surgery

• Project/Area Number: 25461770
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Shimane University
• Principal Investigator: Furuya Motohide 島根大学, 医学部, 助教 (40457172)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: メラトニン / ラメルテオン / 術後せん妄予防 / 心血管バイパス術 / サーカディアンリズム / 病態生理学 / 心血管手術

Outline of Final Research Achievements

Objective: To evaluate if ramelteon prevents postoperative delirium in patients undergoing elective coronary artery bypass grafting. Design: A randomized, open-label study. Participants: A total of 21 patients undergoing elective coronary artery bypass grafting. Intervention: Ramelteon was administered at 9:00 pm for 3 consecutive days included operation date. Measurements: The primary outcome was incidence of postoperative delirium. Secondary outcomes were length of stay in ICU and hospital. Results: The incidence of delirium in the ramelteon group differed significantly from the control group (0% [0/10] vs. 27.3% [3/11]; p = 0.214).Length of stay in ICU in the ramelteon group did not differ significantly from the control group (p = 0.051). Length of stay in hospital in the ramelteon group did not differ significantly from the control group (p = 0.036). Conclusion: Ramelteon might prevent postoperative delirium in patients undergoing elective coronary artery bypass grafting.

Research Products

• [Journal Article] Interkinetic nuclear migration in the mouse embryonic ureteric epithelium: Possible implication for congenital anomalies of the kidney and urinary tract (2016)
  • Author(s): Motoya T, Ogawa N, Nitta T, Rafiq AM, Jahan E, Furuya M, Matsumoto A, Udagawa J, Otani H
  • Journal Title: Congenit Anom Volume: in press Issue: 3 Pages: 127-134
  • DOI: 10.1111/cga.12150
  • NAID: 130008079235
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Effects of yokukansan, a Japanese kampo medicine, for symptoms associated autism spectrum disorder (2016)
  • Author(s): Wake R, Miyaoka T, Furuya M, Hashioka S, Horiguchi J
  • Journal Title: CNS and Neurological Dosorders-Drug Targets Volume: in press
  • Peer Reviewed
• [Journal Article] Efficacy and safety of yokukansan in treatment-resistant schizophrenia: a randomized, multicenter, double-blind, placebo-controlled trial (2015)
  • Author(s): Miyaoka T, Furuya M, Horiguchi J, Wake R, Hashioka S, Thoyama M, Murotani K, Mori N, Minabe Y, Uyo M, Ueno S, Ezoe S, Hoshino S, Seno H
  • Journal Title: Evid Baced Complement Alternat Med Volume: 2015 Pages: 1-11
  • DOI: 10.1155/2015/201592
  • Peer Reviewed
• [Journal Article] Analysis of oxidative stress expressed by urinary level of biopyrrins and 8-hydroxydeoxyguanosine in patients with chronic schizophrenia. (2015)
  • Author(s): Miyaoka T, Ieda M, Hashioka S, Wake R, Furuya M, Liaury K, Hayashida M, Tsuchie K, Arauchi R, Araki T, Shioji I, Ezoe S, Inoue K, Yamaguchi T, Horiguchi J
  • Journal Title: Psychiatry Clin Neurosci Volume: 69(11) Issue: 11 Pages: 693-698
  • DOI: 10.1111/pcn.12319
  • Peer Reviewed / Open Access
• [Journal Article] Novel therapy with ramelteon for hypoactive delirium: A case report (2015)
  • Author(s): Miura S, Furuya M, Yasuda H, Miyaoka T, Horiguchi J
  • Journal Title: J Clin Psychopharmacol Volume: 35 Issue: 5 Pages: 616-618
  • DOI: 10.1097/jcp.0000000000000370
  • Peer Reviewed
• [Journal Article] Ramelteon as adjunctive therapy for delirium referred to a consultation-liaison psychiatry service: a retrospective analysis (2015)
  • Author(s): Furuya M, Miyaoka T, Yasuda H, Wake R, Hashioka S, Miura S, Nagahama M, Araki T, Horiguchi J
  • Journal Title: Int J Geriatr Psychiatry. Volume: 30 Issue: 9 Pages: 994-995
  • DOI: 10.1002/gps.4280
  • Peer Reviewed
• [Journal Article] Efficacy and safety of yokukansan in treatment-resistant schizophrenia: a randomized, double-blind, placebo-controlled trial (a Positive and Negative Syndrome Scale, five-factor analysis) (2015)
  • Author(s): Miyaoka T, Furuya M, Horiguchi J, Wake R, Hashioka S, Tohyama M, Mori N, Minabe Y, Iyo M, Ueno S, Ezoe S, Murotani K, Hoshino S, Seno H.
  • Journal Title: Psychopharmacology Volume: 232 Issue: 1 Pages: 155-64
  • DOI: 10.1007/s00213-014-3645-8
  • Peer Reviewed
• [Journal Article] Regional Cerebral blood flow in late-onset schizophrenia:a SPECT study using 99mTc-ECD. (2015)
  • Author(s): Wake R, Miyaoka T, Araki T, Kawakami K, Furuya M, Limoa E, Hashioka S, Horiguchi J
  • Journal Title: European Archives of Psychiatry and Clinical Neuroscience. Volume: 10 Issue: 1 Pages: 11-11
  • DOI: 10.1007/s00406-015-0607-z
  • Peer Reviewed / Open Access
• [Journal Article] Yokukansan increases serum Brain-derived neurotrophic factor (BDNF) levels in Gunn rat. (2014)
  • Author(s): Furuya M, Miyaoka T, Hashioka S, Wake R, Tsuchie K, Horiguchi J
  • Journal Title: J Brain Sci Volume: 44 Pages: 34-41
  • NAID: 110009913042
  • Peer Reviewed
• [Journal Article] Simple and rapid detection of HLA-A*1:01 for prediction of carbamazepine-induced hypersensitivity using loop-mediated isothermal amplification method (2014)
  • Author(s): Niihara H, Taketani T, Kaneko S, Ito T, Sugamori T, Takahashi N, Miyaoka T, Okazaki S, Yasuda H, Furuya M, Nagahama M, Morita E
  • Journal Title: J Dermatol Sci. Volume: 74 Issue: 1 Pages: 88
  • DOI: 10.1016/j.jdermsci.2013.11.013
  • Peer Reviewed
• [Journal Article] Minocycline improves recognition memory and attenuates microglial activation in Gunn rat: A possible hyperbilirubinemia-induced animal model of schizophrenia (2014)
  • Author(s): Liaury K, Miyaoka T, Tsumori T, Furuya M, Hashioka S, Wake R, Tsuchie K, Fukushima M, Limoa E, Tanra AJ, Horiguchi J
  • Journal Title: Progress in Neuro-Psychopharmacology & Biological Psychiatry Volume: 50 Pages: 184-190
  • DOI: 10.1016/j.pnpbp.2013.12.017
  • Peer Reviewed
• [Journal Article] The effects of combine treatment of memantine and donepezil on Alzheimer’s Disease patients and its relationship with cerebral blood flow in the prefrontal area (2014)
  • Author(s): Araki T, Wake R, Miyaoka T, Kawakami K, Nagahama M, Furuya M, Limoa E, Liaury K, Hashioka S, Murotani K and Horiguchi J.
  • Journal Title: International Journal ofGeriatric Psychiatry Volume: first published online Issue: 9 Pages: 881-889
  • DOI: 10.1002/gps.4074
  • Peer Reviewed
• [Journal Article] Possibility of early withdrawal of benzodiazepine hypnotics by combination with ramelteon for the treatment of insomnia: a pilot study. (2013)
  • Author(s): Furuya M, Miyaoka T, Wake R, Nagahama M, Kawano K, Yamashita S, Ieda M, Ezoe S, Horiguchi J
  • Journal Title: Sleep Biol Rhythms Volume: 11 Pages: 55-61
  • Peer Reviewed
• [Journal Article] The effects of antipsychotics on behavioral abnormalities of the Gunn rat (unconjugated hyperbilirubinemia rat), a rat model of schizophrenia. (2013)
  • Author(s): Tsuchie K, Miyaoka T, Motohide Furuya, Liaury K, Ieda M, Wake R, Horiguchi J, Takechi M
  • Journal Title: Asian J Psychiatry Volume: 6 Issue: 2 Pages: 119-123
  • DOI: 10.1016/j.ajp.2012.09.007
  • Peer Reviewed
• [Journal Article] Yokukansan(TJ-54) for treatment of very-late-onset schizophrenia-like psychosis: an open-label study. (2013)
  • Author(s): Miyaoka T, Wake R, Furuya M, Liaury K, Ieda M, Kawakami K, Tsuchie K, Fukushima M, Ishihara K, Araki T, Hashioka S, Horiguchi J
  • Journal Title: Phytomedicine Volume: 20 Issue: 7 Pages: 654-658
  • DOI: 10.1016/j.phymed.2013.01.007
  • Peer Reviewed
• [Journal Article] Glia: an important target for anti-inflammatory and antidepressant activity. (2013)
  • Author(s): Hashioka S, Miyaoka T, Wake R, Furuya M, Horiguchi J
  • Journal Title: Curr Drug Targets Volume: 14 Issue: 11 Pages: 1322-1328
  • DOI: 10.2174/13894501113146660214
  • NAID: 120006863742
  • Peer Reviewed
• [Journal Article] Yokukansan (TJ-54) for irritability associated with pervasive developmental disorder in children and adolescents: a 12-week prospective, open-label study. (2013)
  • Author(s): Wake R, Miyaoka T, Inagaki T, Furuya M, Ieda M, Liaury K, Kishi K, Horiguchi J
  • Journal Title: J Child Adolesc Psychopharmacol Volume: 23 Issue: 5 Pages: 329-336
  • DOI: 10.1089/cap.2012.0108
  • Peer Reviewed
• [Journal Article] 不眠症治療における（非）ベンゾジアゼピン系睡眠薬へのラメルテオン追加併用の有効性の検討―朝や日中の症状に対する有効性―. (2013)
  • Author(s): 堀口淳, 古屋智英
  • Journal Title: 医学と薬学 Volume: 69 Pages: 783-790
• [Journal Article] Yokukansan promotes hippocampal neurogenesis associated with the suppression of activated microglia in Gunn rat. (2013)
  • Author(s): Furuya M, Miyaoka T, Tsumori T, Liaury K, Hashioka S, Wake R, Tsuchie K, Fukushima M, Ezoe S, Horiguchi J
  • Journal Title: J Neuroinflamation Volume: 10 Issue: 1 Pages: 145-154
  • DOI: 10.1186/1742-2094-10-145
  • Peer Reviewed
• [Presentation] Interkinetic nuclear migration in the developing endoderm- and mesoderm-origin epithelial tubular structures (2016)
  • Author(s): Otani H, Motoya T, Ogawa N, Nitta T, Rafiq AM, Jahan E, Kaneda R, Furuya M, Matsumoto A, Udagawa J, Hatta T
  • Organizer: 第121回日本解剖学会全国学術集会
  • Place of Presentation: ビックパレット福島（郡山市）
  • Year and Date: 2016-03-28
• [Presentation] Analysis of oxidative stress expressend by urinary level of biopyrrins and 8-hydroxydeoxyguanosine in patients with chronic schizophrenia (2016)
  • Author(s): Miyaoka T, Ieda M, Hashioka S, WakeR, Furuya M, Hayashida M, Horiguchi J
  • Organizer: The 11th Annual Meeting of Japanese Society of Schizophrenia Research
  • Place of Presentation: ベイシア文化ホール（前橋市）
  • Year and Date: 2016-03-25
• [Presentation] 統合失調症におけるPANSSと脳血流の関係 (2016)
  • Author(s): 和氣玲, 宮岡剛, 古屋智英, Erlyn Limoa, 橋岡禎征, 堀口淳
  • Organizer: 第11回日本統合失調症学会
  • Place of Presentation: ベイシア文化ホール（前橋市）
  • Year and Date: 2016-03-25
• [Presentation] 妊娠・出産に対する不安に半夏厚朴湯が有用であった精神疾患合併妊婦の2症例 (2015)
  • Author(s): 長濱道治, 松田泰行, 三木啓之, 金山三紗子, 田中一平, 三浦章子, 山下智子, 河野公範, 古屋智英, 岡崎四方, 林田麻衣子, 和氣玲, 橋岡禎征, 宮岡剛, 堀口淳
  • Organizer: 第56回中国・四国精神神経学会
  • Place of Presentation: 倉敷市芸文館（倉敷市）
  • Year and Date: 2015-11-12
• [Presentation] マウス胎仔尿管の伸長過程における上皮細胞核の再配置 (2015)
  • Author(s): 元矢 知志、新田 哲哉、Rafiq Ashiq Mahmood、Jahan Esrat、小川 典子、古屋 智英、松本 暁洋、宇田川 潤、大谷 浩
  • Organizer: 日本解剖学会第70回中国・四国支部学術集会
  • Place of Presentation: 愛媛大学城北キャンパス南加記念ホール（松山市）
  • Year and Date: 2015-10-24
• [Presentation] マウス腸管の発生過程における腸管上皮細胞数とInterkinetic nuclear migration (INM)の解析 (2015)
  • Author(s): 新田哲哉、小川典子、倉本純子、元矢知志、古屋智英、Rafiq Ashiq Mahmood、Jahan Esrat、松本 暁洋、大谷 浩
  • Organizer: 日本解剖学会第70回中国・四国支部学術集会
  • Place of Presentation: 愛媛大学城北キャンパス南加記念ホール（松山市）
  • Year and Date: 2015-10-24
• [Presentation] マウス尿管の発生過程におけるInterkinetic nuclear migrationおよびConvergent extensionの解析 (2015)
  • Author(s): 元矢知志、新田哲哉、Rafiq Ashiq Mahmood、Jahan Esrat、小川 典子、古屋 智英、松本 暁洋、宇田川 潤、大谷 浩
  • Organizer: 第55回日本先天異常学会学術集会、第38回日本小児遺伝学会学術集会合同開催
  • Place of Presentation: パシフィコ横浜会議センター（横浜市）
  • Year and Date: 2015-07-25
• [Presentation] マウス腸管の発生過程における腸管上皮細胞数とInterkinetic nuclear migration (INM) の変化 (2015)
  • Author(s): 新田哲哉、小川典子、倉本純子、元矢知志、古屋智英、Rafiq Ashiq Mahmood、Jahan Esrat、松本 暁洋、大谷 浩
  • Organizer: 第55回日本先天異常学会学術集会、第38回日本小児遺伝学会学術集会合同開催
  • Place of Presentation: パシフィコ横浜会議センター（横浜市）
  • Year and Date: 2015-07-25
• [Presentation] 器官形成期マウス胚の気管・食道上皮におけるinterkinetic nuclear migrationの解析 (2015)
  • Author(s): 兼田 稜、橋本龍樹、荒内亮輔、古屋智英、佐藤文夫、宇田川 潤、大谷 浩
  • Organizer: 第55回日本先天異常学会学術集会、第38回日本小児遺伝学会学術集会合同開催
  • Place of Presentation: パシフィコ横浜会議センター（横浜市）
  • Year and Date: 2015-07-25
• [Presentation] 心血管バイパス手術におけるラメルテオンの術後せん妄予防に関する予備的研究：無作為ランダム化オープン試験 (2015)
  • Author(s): 古屋智英、末廣章一、南 浩太郎、織田禎二、斎藤洋司、大谷 浩、宮岡 剛、堀口 淳
  • Organizer: 第63回山陰精神神経学会
  • Place of Presentation: 鳥取大学医学部臨床講義棟（米子市）
  • Year and Date: 2015-07-04
• [Presentation] 貯蔵鉄不足を伴った精神疾患に鉄剤が奏功した経験. (2015)
  • Author(s): 古屋智英、宮岡 剛、和氣 玲、長濱道治、田中一平、堀口 淳
  • Organizer: 第63回山陰精神神経学会
  • Place of Presentation: 鳥取大学医学部臨床講義棟（米子市）
  • Year and Date: 2015-07-04
• [Presentation] 老年期の不安症に対する漢方薬治療（シンポジウム） (2014)
  • Author(s): 古屋智英
  • Organizer: 第7回日本不安症学会
  • Place of Presentation: アステールプラザ（広島市中区）
  • Year and Date: 2014-10-25
• [Presentation] Yokukansan (TJ-54) for irritability associated with pervasive developmental disorder in children and adolescents a 12-week prospective, open-label study. (2013)
  • Author(s): Wake R, Miyaoka T, Inagaki T, Furuya M, Ieda M, Liaury K, Kishi K, Horiguchi J
  • Organizer: The 7th Annual scientific meeting Hong Kong society of biological psychiatry.
  • Place of Presentation: Eaton Smart Hong Kong, Hong Kong
• [Presentation] Efficacy and safety of Yokukansan (TJ-54) for treatment-resistant schizophrenia: a randomized, multi-centre, double-blind, placebo-controlled trial. (2013)
  • Author(s): Miyaoka T, Furuya M, Horiguchi J, Wake R, Hashioka S, Toyama M, Daimon T, Mori N, Minabe Y, Iyo M, Ueno S, Ezoe S, Hoshino S, Seno H
  • Organizer: Society of biological psychiatry 68th annual meeting.
  • Place of Presentation: Hilton Union Square, San Francisco, USA
• [Presentation] Efficacy and safety of yokukansan (TJ-54) for treatment-resistant schizophrenia: a randomised placebo-controlled trial. (2013)
  • Author(s): Miyaoka T, Furuya M, Horiguchi J, Wake R, Hayashida S, Toyama M, Daimon T, Mori N, Minabe Y, Iyo M
  • Organizer: 26th ECNP
  • Place of Presentation: Barcelona, Spain
• [Presentation] The effects of minocycline on microglial cells activation in the dentate gyrus of Gunn rat: a possible animal model of schizophrenia. (2013)
  • Author(s): リアウリ・クリスティアン, 宮岡剛, 津森登志子, 和氣玲, 古屋智英, 家田麻紗, 土江景子, 福島美千代, タンラ・ジャヤランカラ, 堀口淳
  • Organizer: 第8回日本統合失調症学会
  • Place of Presentation: 浦河町総合文化会館、北海道浦河郡浦河町
• [Presentation] 治療抵抗性統合失調症に対する抑肝散の有用性に関する二重盲検試験. (2013)
  • Author(s): 宮岡剛, 堀口淳, 遠山正彌, 澤芳樹, 大門貴志, 名井陽, 江副幸子, 森則夫, 三辺義雄, 伊豫雅臣, 上野修一, 古屋智英, 和氣玲, 橋岡禎征
  • Organizer: 第109回日本精神神経学会学術総会
  • Place of Presentation: 福岡国際会議場、福岡市
• [Presentation] Yokukansan for irritability associated with PDDs. Open-label study. (2013)
  • Author(s): 和氣玲, 宮岡剛, 稲垣卓司, 古屋智英, 橋岡禎征, 岸和子, 堀口淳
  • Organizer: 第109回日本精神神経学会学術総会
  • Place of Presentation: 福岡国際会議場、福岡市
• [Presentation] The effects of minocycline on microglial cells in the dentate gyrus of Gunn rat - a possible animal model of schizophrenia―. (2013)
  • Author(s): Liaury K, Miyaoka T, Tsumori T, Wake R, Furuya M, Ieda M, Tsuchie K, Fukushima M, Tanra AJ, Horiguchi J
  • Organizer: 第28回日本老年精神医学会
  • Place of Presentation: 大阪国際会議場、大阪市
• [Presentation] Minocycline improve prepulse inhibition (PPI) deficits through inhibition of microglial activation in the dentate gyrus of Gunn rat: a neuroinflammatory animal model of schizophrenia. (2013)
  • Author(s): Liaury K, Miyaoka T, Tsumori T, Furuya M, Wake R, Ieda M, Tsuchie K, Fukushima M, Tanra AJ, Horiguchi J
  • Organizer: The 36th Annual Meeting of the Japan Neuroscience Society
  • Place of Presentation: Kyoto International Conference Center, Kyoto, Janan
• [Presentation] The correlation between psychiatric symptoms and regional cerebral blood flow in first episode schizophrenia patients. (2013)
  • Author(s): Wake R, Miyaoka T, Kawakami K, Furuya M, Liaury K, Hashioka S, Horiguchi J
  • Organizer: 11th World Congress of Biological Psychiatry
  • Place of Presentation: Kyoto International Conference Center, Kyoto, Janan
• [Presentation] レビー小体型認知症が疑われた薬剤誘発性せん妄にramelteonが奏効した軽度認知障害の1例 (2013)
  • Author(s): 田中一平, 古屋智英, 安田英彰, 和氣玲, 橋岡禎征, 宮岡剛, 堀口淳
  • Organizer: 第61回山陰精神神経学会
  • Place of Presentation: 鳥取大学医学部、米子市
• [Presentation] Yokukansan (TJ-54) in the treatment of irritability associated with pervasive developmental desorder in children and adolescents aged 6-17 years. (2013)
  • Author(s): Wake R, Miyaoka T, Inagaki T, Furuya M, Liaury K, Limoa E, Hashioka S, Kishi K, Horiguchi J
  • Organizer: 第61回山陰精神神経学会
  • Place of Presentation: 鳥取大学医学部、米子市
• [Presentation] 治療抵抗性統合失調症に対する抑肝散の有用性に関する研究―PANSS 5因子解析― (2013)
  • Author(s): 宮岡剛, 古屋智英, Rei Wake, 橋岡禎征, 堀口淳, 遠山正彌, 森則夫, 三辺義雄, 伊豫雅臣, 上野修一
  • Organizer: 第23回日本臨床精神神経薬理学会第43回日本神経精神薬理学会合同年会
  • Place of Presentation: 沖縄コンベンションセンター、宜野湾市
• [Presentation] Minocycline improves recognition memory and attenuates microglial activation in Gunn rat: a possible hyperbilirubinemia-induced animal model of schizophrenia (2013)
  • Author(s): Liaury Kristian, 宮岡剛, 津森登志子, 古屋智英, 橋岡禎征, 和氣玲, 土江景子, 福島美千代, Limoa Erlyn, Andi Jayalangkara Tanra, 堀口淳
  • Organizer: 第54回中国・四国精神神経学会
  • Place of Presentation: サンポートホール高松、高松市