FTD off - label 79 FTD Boxer et al., 2012b Alzheimer s disease : AD Cholinesterase inhibitor : ChEI FTD FTD Mendez et al., 2007 FTD Kerssens et al., 2
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1 78 Dementia Japan 29 : 78-85, 原著 要旨 4 FTD /3 Off - label medication for frontotemporal dementia in Japan Shunichiro Shinagawa 1, Yusuke Yatabe 2, Kazue Shigenobu 3, Ryuji Fukuhara 2, Mamoru Hashimoto 2, Manabu Ikeda 2, Kazuhiko Nakayama Department of Psychiatry, Jikei University School of Medicine Nishi - shinbashi, Minato - ku, Tokyo , Japan Department of Psychiatry and Neuropathobiology, Faculty of Life Sciences, Kumamoto University Honjo, Chuo - ku, Kumamoto , Japan Asakayama Hospital Imaikemachi, Sakai - ku, Sakai - city, Osaka , Japan FTD : off - label 1. はじめに frontotemporal dementia : FTD Alzheimer s disease : AD Ratnavalli et al., 2002 FTD Rascovsky et al., 2011 Mioshi et al., 2013 Woolley et al., 2011
2 FTD off - label 79 FTD Boxer et al., 2012b Alzheimer s disease : AD Cholinesterase inhibitor : ChEI FTD FTD Mendez et al., 2007 FTD Kerssens et al., 2008 FTD FTD 対象と方法 FTD Mini mental state examination : MMSE Folstein et al., 1975 ChEI 2010 ChEI Donepezil χ 2 Fisher 2 t χ 2 Fisher 3. 結果 3.1. 患者および紹介医の背景 MMSE 18.4 FTD Frontotemporal lobar degeneration : FTLD Frontotemporal dementia with motor neuron disease : FTD - MND FTD 認知症に対する薬剤を使用していた例 % 43 23% 20 ChEI 20.7% % 2 : 35.6% 31 ChEI 16.1% % 10
3 80 Dementia Japan Vol. 29 No. 1 January 2015 表 1. demographic data of patients and referring physicians Sex Male : Female 42 : 45 Age education year disease duration year MMSE score Referring physicians diagnosis FTD/FTLD/temporal variant/pick s disease/ftd - MND Referring physicians background psychiatrist/neurologist/general physician/neurosurgeon/others /5/9/11/7 53/17/9/6/2 MMSE : Mini - Mental State Examination FTD : Frontotemporal dementia FTLD : Frontotemporal Lobar Degeneration FTD - MND : FTD with motor neuron disease mean SD for Age, education, disease duration, and MMSE score 10.3% 9 9.2% 8 1.1% 診療科別の処方 ChEI 13/ % 2/ % 2/9 22.2% 1/8 12.5% χ 2 Fisher 26/ % 1/17 5.9% 2/9 22.2% 2/8 25.0% χ 2 Fisher P= 紹介医の診断別の処方 ChEI 18 FTD % FTLD FTD - MND ChEI 31 FTD % FTLD FTD - MND 3.5. 専門医の診断と紹介医の処方 ChEI 18 FTD % ChEI 69 FTD % χ 2 Fisher 31 FTD % 56 FTD % FTD χ 2 Fisher 3.6. 薬剤の使用に影響を与える背景因子 ChEI ChEI 2 2
4 FTD off - label 81 表 2. Factors associated with ChEI use No ChEI use n=69 ChEI use n=18 Sex Male : Female 33 : 36 9 : 9 n.s Age n.s education year n.s disease duration year n.s MMSE score n.s care insurance use yes : no 20 : 49 5 : 13 n.s ChEI : Cholinesterase Inhibitor MMSE : Mini - Mental State Examination mean standard deviation for Age, education, disease duration, and MMSE score 表 3. Factors associated with psychotropic drug use No psychotropic drug use n=56 psychotropic drug use n=31 Sex Male : Female 26 : : 15 n.s Age n.s education year n.s disease duration year n.s MMSE score n.s care insurance use yes : no 19 : 37 6 : 25 n.s MMSE : Mini - Mental State Examination mean standard deviation for Age, education, disease duration, and MMSE score MMSE MMSE 2 4. 考察 FTD off - label ChEI 2 1/3 ChEI FTD FTD FTD Woolley et al., 2011 FTD 2 ChEI 1/3 ChEI 2
5 82 Dementia Japan Vol. 29 No. 1 January 2015 Dementia with Lewy bodies : DLB ChEI Mori RCT Mori et al., 2012 ChEI FTD ChEI Kertesz et al., 2008 ; Mendez et al., 2007 Mendez et al., 2007 FTD ChEI 2009 ChEI 2 FTD ChEI ChEI 18 ChEI 69 FTD 3 Behavioral and psychological symptoms of dementia : BPSD AD FTD ChEI ChEI ChEI Galantamine Rivastagmine Memantine Memantine BPSD Gauthier et al., 2008 BPSD Memantine Memantine Boxer et al., 2012a Memantine 35%? % % BPSD 93% 81% 47% 2006 FTD? FTD selective serotonin reuptake inhibitor : SSRI Swartz FTD SSRI Swartz et al., 1997 Ikeda et al., 2003 ; Mendez et al., 2005 ; Moretti et al., 2002 SSRI Lebert et al., 2004 FTD
6 FTD off - label 83 1 BPSD FTD Kerssens et al., 2008 FTLD BPSD % Pijnenburg et al., 2003 FTD 5 Kimura et al., FTD 16.1% 33.9% FTLD FTD - MND ChEI ChEI 4 FTD - MND off - label FTD 5. まとめ FTD off - label ChEI FTD 謝辞
7 84 Dementia Japan Vol. 29 No. 1 January 2015 文献 Boxer AL, Knopman DS, Kaufer DI, Grossman M, Onyike C, Graf - Radford N, et al 2012a Memantine in Patients with Frontotemporal Lobar Degeneration : a Multicentre, Randomised, Double - Blind, Placebo - Controlled Trial. The Lancet Neurology 12 : Boxer AL, Gold M, Huey E, Gao FB, Burton EA, Chow T, et al 2012b Frontotemporal Degeneration, the Next Therapeutic Frontier : Molecules and Animal Models for Frontotemporal Degeneration Drug Development. Alzheimer s & Dementia 9 : Folstein MF, Folstein SE, McHugh PR 1975 Mini - Mental State. a Practical Method for Grading the Cognitive State of Patients for the Clinician. Journal of Psychiatric Research 12 : Gauthier S, Loft H, Cummings J 2008 Improvement in Behavioural Symptoms in Patients with Moderate to Severe Alzheimer s Disease by Memantine : a Pooled Data Analysis. International Journal of Geriatric Psychiatry 23 : Ikeda M, Shigenobu K, Fukuhara R, Hokoishi K, Maki N, Nebu A, et al 2003 Efficacy of Fluvoxamine as a Treatment for Behavioral Symptoms in Frontotemporal Lobar Degeneration Patients. Dementia and Geriatric Cognitive Disorders 17 : Kerssens, CJ, Pijnenburg YA 2008 Vulnerability to Neuroleptic Side Effects in Frontotemporal Dementia. European Journal of Neurology 15 : Kertesz A, Morlog D, Light M, Blair M, Davidson W, Jesso S, et al 2008 Galantamine in Frontotemporal Dementia and Primary Progressive Aphasia. Dementia and Geriatric Cognitive Disorders 25 : Kimura T, Hayashida H, Furukawa D, Miyauchi D, Takamatsu J 2009 Five Cases of Frontotemporal Dementia with Behavioral Symptoms Improved by Yokukansan. Psychogeriatrics 9 : Lebert F, Stekke W, Hasenbroekx C, Pasquier F 2004 Frontotemporal Dementia : a Randomised, Controlled Trial with Trazodone. Dementia and Geriatric Cognitive Disorders 17 : Mendez MF, Shapira J, McMurtray A, Licht E 2007 Preliminary Findings : Behavioral Worsening on Donepezil in Patients with Frontotemporal Dementia. American Journal of Geriatric Psychiatry 15 : Mendez MF, Shapira J, Miller BL 2005 Stereotypical Movements and Frontotemporal Dementia. Movement disorders 20 : Mioshi E, Foxe D, Leslie F, Savage S, Hsieh S, Miller L, et al 2013 The Impact of Dementia Severity on Caregiver Burden in Frontotemporal Dementia and Alzheimer Disease. Alzheimer Dis Assoc Disord 27 : Moretti R, Torre P, Antonello RM, Cazzato G, Bava A 2002 Frontotemporal Dementia : Paroxetine as a Possible Treatment of Behavior Symptoms. a Randomized, Controlled, Open 14 - Month Study. European Neurology 49 : Mori E, Ikeda M, Kosaka K, Donepezil - DLB Study Investigators 2012 Donepezil for Dementia with Lewy Bodies : a Randomized, Placebo - Controlled Trial. Annals of Neurology 72 : Pijnenburg YA, Sampson EL, Harvey RJ, Fox NC, Rossor MN 2003 Vulnerability to Neuroleptic Side Effects in Frontotemporal Lobar Degeneration. International Journal of Geriatric Psychiatry 18 : Rascovsky K, Hodges JR, Knopman D, Mendez MF, Kramer JH, Neuhaus J, et al 2011 Sensitivity of Revised Diagnostic Criteria for the Behavioural Variant of Frontotemporal Dementia. Brain 134 : Ratnavalli E, Brayne C, Dawson K, Hodges JR 2002 The Prevalence of Frontotemporal Dementia. Neurology 58 : Swartz JR, Miller BL, Lesser IM, Booth R, Darby A, Wohl M, et al 1997 Behavioral Phenomenology in Alzheimer's Disease, Frontotemporal Dementia, and Late - Life Depression : a Retrospective Analysis. Journal of Geriatric Psychiatry and Neurology 10 : Woolley JD, Khan BK, Murthy NK, Miller BL, Rankin KP 2011 The Diagnostic Challenge of Psychiatric Symptoms in Neurodegenerative Disease. Journal of Clinical Psychiatry 72 : : BPSD 17 :
8 FTD off - label 85 Off - label medication for frontotemporal dementia in Japan Shunichiro Shinagawa 1, Yusuke Yatabe 2, Kazue Shigenobu 3, Ryuji Fukuhara 2, Mamoru Hashimoto 2, Manabu Ikeda 2, Kazuhiko Nakayama 1 1 Department of Psychiatry, Jikei University School of Medicine 2 Department of Psychiatry and Neuropathobiology, Faculty of Life Sciences, Kumamoto University 3 Asakayama Hospital In order to clearly the situation of off - label medication in Japan, we investigated the medication and demographic data of consecutive 87 subjects those were referred with the diagnosis of Frontotemporal dementia FTD syndrome. 60% of referring physicians were psychiatrists, followed by were neurologists, general physician, neurosurgeon, and other physicians. Half of the subjects were treated with some kind of medications for dementia. Cholinesterase inhibitor is prescribed for 20% of all subjects by various physicians, while psychotropic drugs were prescribed for 35% of all subjects mainly by psychiatrists. Antidepressant and antipsychotics are most common among them. Other background factors such as age, sex, duration, and MMSE scores are not associated with medication use. We need to establish guideline of pharmacological treatment for patients with FTD. Key wards : Frontotemporal dementia, off - label medication, cholinesterase inhibitor, psychotropic drugs, pharmacological treatment Address correspondence to Dr. Shunichiro Shinagawa, Department of Psychiatry, The Jikei University School of Medicine Nishi - shinbashi, Minato - ku, Tokyo , Japan
606 Dementia Japan Vol. 29 No. 4 October 2015 Table 1. The day care for people with severe dementia Outline Subjects Personal distribution Medical man
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118 Dementia Japan Vol. 31 No. 1 January 2017 表 1. DLB に対して mect を行った先行研究 Rasmussen K 2003 USA Japan Japan Japan Japan 1 2
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