| Project/Area Number |
18K07607
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 52030:Psychiatry-related
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| Research Institution | University of the Ryukyus |
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Principal Investigator |
Mihara Kazuo 琉球大学, 医学(系)研究科(研究院), 客員研究員 (30302029)
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| Co-Investigator(Kenkyū-buntansha) |
近藤 毅 琉球大学, 医学(系)研究科(研究院), 教授 (40215455)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2020: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2019: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2018: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
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| Keywords | 難治性うつ病性障害 / ラモトリギン / 血漿濃度 / UGT / 遺伝子多型 / UGT2B7 / TNF-α / 治療反応性 / 腫瘍壊死因子 / サイトカイン |
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| Outline of Final Research Achievements |
Lamotrigine, which exerts antidepressive effect maily by lowering tumor necrosis factor, was used to treat refractory depressive disorder, and it has been shown that a partial response at week 4 can predict subsequent outcome at week 8. In addition, it has been suggested that a high plasma lamotrigine concentration during week 2 is risk factor for lamotrigine-related rash, and a plasma lamotrigine concentration of 4.38 μgmol/L may be a considered a threshold for rash in refractory depressive disorder. Although, the identification of genetic polymorphism metabolizing lamotrigine does not allow the optimal dose of lamotrigine, it can predict at least partially the therapeutic response to lamotrigine in the treatment of refractory depressive disorder
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| Academic Significance and Societal Importance of the Research Achievements |
難治性うつ病性障害に腫瘍壊死因子を抑制するラモトリギンの投与が有用であり、その臨床反応性が治療開始2週目、4週目といった治療初期の段階で予測が可能であることを示した。また、ラモトリギン代謝酵素の活性を規定する遺伝子多型を同定することで、部分的ではあるが治療開始前に治療反応性を予測する可能性を示した。
本研究は難治性うつ病性障害の治療に腫瘍壊死因子低下作用を有する薬物の有用性を示唆するものであり、その合理的治療指針に一定の論拠を与えると考えられる
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