アルツハイマー病における高用量donepezilの治療効果

Clinical Effects of High Oral Dose of Donepezil in Patients with Alzheimer's Disease

抄録

　高度アルツハイマー病の認知機能障害に対しdonepezil 10mgがわが国においても認可された。今回57名のアルツハイマー病患者に対し10mgへ増量した際の効果と副作用，アポリポ蛋白E4との関連について検討した。その結果，投与開始2か月間においてdonepezil 10mgの効果はアルツハイマー病の重症度，donepezil 5mg内服期間，アポリポ蛋白E遺伝子型には関係なく認知機能障害の進行を抑制できると考えられた。副作用出現率は12.3％と治験時の40％以上の副作用出現率と比較し低値であり，5mgを長期間内服していることが，10mgに増量した際の副作用の軽減につながる可能性が示唆された。

　A daily dose of 10mg donepezil for severe Alzheimer's disease (AD) patients was licensed in Japan since the end of August 2007；but most Japanese patients with AD are prescribed a daily dose of 5mg donepezil for more than 4 weeks. In addition, it has been confirmed in foreign countries that a daily dose of 10mg of donepezil is effective for mild-to-moderate AD patients. We initiated medical treatment in 57 AD patients at a daily dose of 10mg donepezil and subsequently assessed examined the clinical effects, adverse effects, and the relation with apolipoprotein E4 in these patients. We observed that a daily dose of 10mg donepezil could stabilize or slow down the progression of cognitive impairment in our patients. The severity of AD, the duration of medication with 5mg donepezil and the apolipoprotein E genotype did not influence any clinical effects. The incidence of adverse effects in this study was 12.3%, which was considerably lower than the incidence rate of 40% in the previous clinical trial in Japan. These findings suggest that long-term medication with a daily dose of 5mg donepezil might be associated with fewer adverse effects.