Rinsho Shinkeigaku (Clinical Neurology)

Case Report

Paradoxical effect of levetiracetam on seizure suppression: three cases showing U curve association between dose and effect

Takeshi Inoue, M.D.1), Katsuya Kobayashi, M.D., Ph.D.1), Kiyohide Usami, M.D., Ph.D.2), Akihiro Shimotake, M.D., Ph.D.1), Morito Inouchi, M.D., Ph.D.2)3), Tatsuya Sakai, M.D., Ph.D.4), Akio Ikeda, M.D., Ph.D.2) and Ryosuke Takahashi, M.D., Ph.D.1)

1) Department of Neurology, Kyoto University Graduate School of Medicine
2) Department of Epilepsy, Movement Disorders and Physiology, Kyoto University Graduate School of Medicine
3) Department of Neurology, Kyoto City Hospital
4) General Internal Medicine, Horikawa Hospital

We experienced 3 adult patients with intractable focal epilepsy treated by levetiracetam (LEV) as polytherapy, who showed paradoxical effect (PE). Starting dose of LEV was small (62.5, 250 mg/day) and we gradually increased by less than 250 mg/day, every more than 2 weeks. Within 6 months after LEV was added, LEV of 750 to 1,000 mg/day brought reduction of seizure frequency. Serum concentration of LEV was 13.3 and 14.0 µg/ml. In order to obtain better seizure control, LEV was increased up to 1,000-2,500 mg/day (19.3-35.0 µg/ml) within one year, and they developed PE. They all showed increased habitual seizures, occurring in cluster. Once dose of LEV deceased down to what produced the maximum seizure suppression, all of the patients regained the better seizure control. It is most likely that at least in some patients like present 3 cases, PE of LEV may express U curve association between dose and effect and that it was only delineated by slow titration.
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(CLINICA NEUROL, 61: 247−252, 2021)
key words: antiepileptic drug, paradoxical effect, serum concentration, focal epilepsy

(Received: 2-Oct-20)