てんかんの新しい治療薬

Newer Antiepileptic Drugs

はじめに

　てんかんはありふれた疾患であり，年間の発症頻度は10万人に対して30～50人，有病率は1,000人に対して6～8人，累積罹患率は3％に達する^1）。治療の主体は抗てんかん薬による発作の抑制であり，多くの例が長期間の服薬を要し，ときに治療は生涯にわたる。1990年までに6種類の主要な抗てんかん薬（カルバマゼピン：CBZ，フェニトイン：PHT，バルプロ酸：VPA，フェノバルビタール：PB，プリミドン：PRM，エトサクシミド：ESM）が用いられてきた。新たに発症したてんかんの約半数は，これらの従来型抗てんかん薬の投与により，すみやかに発作が抑制される。その他の20～30％の例も，従来薬の追加・変更により発作が改善する。残りの20～30％が従来薬では発作が抑制されない難治てんかんとなる。難治の定義は必ずしも統一されていないが，従来薬の単剤治療を2剤試み，さらに従来薬の併用療法を一度試みても，発作が抑制されない場合をいうことが多い^2）。このような難治例には外科治療を含む新たな治療戦略が必要となるが，新しい抗てんかん薬もその選択肢となる。

Abstract

　Ten newer antiepileptic drugs have been developed since 1990s. These drugs have wider therapeutic spectra, fewer side-effects, and lesser drug-to-drug interactions compared with the older typical antiepileptic drugs. Among them, zonisamide was developed in Japan and has been used from 1989. Gabapentin was at length approved in 2006. The other newer antiepileptic drugs are not approved yet in Japan. Felbamate can not be used in Europe because it may induce lethal hepatic toxicity and aplastic anemia. Vigabatrin is not approved in USA because it may induce permanent visual field deficit. The USA guideline for epilepsy treatment recommends that patients with newly diagnosed epilepsy can be treated with gabapentin, lamotrigine, topiramate, and oxcarbazepine. In contrast, based on epilepsy treatment guideline in England, newer antiepileptic drugs are considered only when patients with newly diagnosed epilepsy are unable to use the older antiepileptic drugs for some reasons. All newer antiepileptic drugs are used for intractable partial epilepsies, and lamotrigine and topiramate can also be used for idiopathic generalized epilepsies. The response rate (seizure reduction rate with 50% or more) and dropout rate are overlapping among all newer antiepileptic drugs. Gabapentin, levetiracetam, and pregabalin are eliminated from kidney, and they had no drug-to-drug interactions and can be titrated rapidly. The serum concentration of lamotrigine is decreased with co-administration of hepatic enzyme inducing drugs and is increased with co-administration of valproic acid. Hypersensitivity reactions are rare with gavapentin, levetiracetam, topiramate, and tiagabin. Psychoses are reported to be induced with zonisamide, however, they can be induced with the other newer drugs (topiramate, levetiracetam, etc.). Drug-induced psychiatric symptoms, especially depression, may be often underdiagnosed. Many of these newer drugs (gabapentine, lamotrigine, levetiracetam, oxycarbazepine, etc.) have effects on chronic neuropathic pain. Some newer drugs show mood stabilizing effects (lamotrigine,oxycarbazepine,etc.),or antianxiety effect (gabapentin, topiramate, levetiracetam, pregavalin, etc.). Wide range of action to central nervous system of these newer antiepileptic drugs may serve not only for clinical seizure suppression, but also for neuroprotection．