Photosensitive epilepsy: a model to study the effects of antiepileptic drugs. Evaluation of the piracetam analogue, levetiracetam

Abstract

General rightsIt is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulationsIf you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: http://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. AbstractThe experimental antiepileptic drug, levetiracetam (UCB L059), a piracetam analogue has been investigated in photosensitive patients in the "photosensitivity model", an early phase II study. A total of 12 patients (10 females, 2 males) with a mean age of 21.5 years (range 13-38) were investigated during a 3 day period in 3 centres (France, The Netherlands, Germany), using the same standardised method. The subjects were either treated with a single oral dose of 250 mg, 500 mg, 750 mg or 1000 mg. In addition, 4 patients took 250 mg b.i.d, for 3-5 days, after which they were re-examined. In 9 of 12 photosensitive patients (75%) a clear suppression (3 patients) or abolishment (6 patients) of IPS evoked photoparoxysmal EEG responses was found. This effect appeared to be dose-dependent, the higher the dose the greater the effect; complete abolishment was only seen at dosages of 750 mg and 1000 mg, occurring at peak plasma levels and lasting between 6 and 30 h. There was no indication of pharmacokinetic interaction with concomitant antiepileptic drugs such as valproic acid, ethosuximide or phenobarbitone. No serious side-effects were seen and some patients reported enhancement of their mood. Two patients with myoclonic jerks noticed a clear reduction of their myoclonus, although this was not one of the objectives of the study. In conclusion, levetiracetam showed a clear antiepileptic effect in the photosensitivity model.

Levetiracetam in juvenile myoclonic epilepsy: long‐term efficacy in newly diagnosed adolescents

“…[13][14][15][16] Moreover, LEV has been shown to be effective in preventing the photoparoxysmal response in patients with photosensitive epilepsy. 17 Furthermore, LEV's pharmacokinetic profile makes this AED a good option for the treatment of paediatric patients. 18,19 Preliminary data from a recent multicentre, double-blind, randomized, placebo-controlled trial evaluating LEV as addon treatment in refractory idiopathic generalized epilepsy with myoclonic seizures showed a 21.3 and a 3.4% seizurefree rate associated with LEV therapy and placebo respectively.…”

Effects of Marketed Antiepileptic Drugs and Placebo in the Human Photosensitivity Screening Protocol

“…All IPS assessments were performed using the systematic protocol previously described by Kasteleijn et al [2]. A standardized EEG photic stimulation procedure was used: 5 s of intermittent white flashes by a Grass PS 33 photic stimulator (1 Joule) with a 7-s pause.…”

“…If patients with a relatively stable IPS response are used as patients, studies can be performed using a study design that requires only 5-6 patients per dose tested. This protocol has been used to identify the antiepileptic effect of a number of AEDs (some now approved, some still in development), most notably levetiracetam (LEV), lamotrigine (LTG), brivaracetam, carisbamate, JZP4, YKP3089, and valproate (VPA) [1][2][3][4][5][6]. Drugs also have been tested that are sedatives, but not anticonvulsants, and these have failed to suppress photosensitivity [7], indicating that the assessment of PPR is both sensitive and specific.…”

“…As many patients with photosensitivity have generalized epilepsy and generalized spike-wave, there is controversy as to whether CBZ is effective in the photosensitivity model. The second drug was LEV, which is considered to be effective in both focal and generalized epilepsy ("broad-spectrum"), and has already been proven to be effective in standard inpatient photosensitivity trial design [2]. We used this drug to determine "assay sensitivity" for our new design.…”

Efficacy and Tolerability of Levetiracetam (Keppra®) in the Treatment of Epilepsy: Review of Literature

“…В результате исследования авторы сделали вывод о вы-сокой эффективности леветирацетама в блокировании интериктальных эпилептиформных разрядов и фото-пароксизмального ответа на ЭЭГ [87]. Ранее D. G. Kasteleijn-Nolst Trenite et al (1996) показали эф-фективность леветирацетама в блокировании фотосен-ситивности у больных эпилепсией [52].…”