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Epilepsy Res. 2021 Feb;170:106547. doi: 10.1016/j.eplepsyres.2020.106547. Epub 2021 Jan 04.

Risk factors of paradoxical reactions to anti-seizure medication in genetic generalized epilepsy.

Epilepsy research

Joanna Gesche, Helle Hjalgrim, Guido Rubboli, Christoph Patrick Beier

Affiliations

  1. Department of Neurology, Odense University Hospital, Denmark; Department of Clinical Research, University of Southern Denmark, Denmark.
  2. Danish Epilepsy Center, Dianalund, Denmark.
  3. Danish Epilepsy Center, Dianalund, Denmark; Institute of Clinical Medicine, University of Copenhagen, Denmark.
  4. Department of Neurology, Odense University Hospital, Denmark; Department of Clinical Research, University of Southern Denmark, Denmark; OPEN, Open Patient Data Explorative Network, Odense University Hospital, Denmark. Electronic address: [email protected].

PMID: 33421702 DOI: 10.1016/j.eplepsyres.2020.106547

Abstract

This study aimed at providing valid estimates for the risk of clinically relevant seizure aggravation by recommended anti-seizure medications in patients with Genetic Generalized Epilepsy (GGE). To this aim, treatment response, side effects and paradoxical reactions to anti-seizure treatment were retrospectively assessed in a near-population based cohort comprising 471 adult GGE patients. A total of 1046 treatment attempts were analyzed (lamotrigine: 351, valproic acid: 295, levetiracetam: 249, primidone/phenobarbital: 94, zonisamide: 57). Under lamotrigine, seizure aggravation was observed in 15 patients (two patients during levetiracetam, one patient during zonisamide, none during phenobarbital and valproic acid). All but two patients with paradoxical reactions to lamotrigine were diagnosed with juvenile myoclonic epilepsy (JME), otherwise, the clinical and electroencephalographic characteristics of patients with paradoxical reactions did not differ. At treatment start, the estimated risk of a paradoxical reaction to lamotrigine was 7.9 % in JME patients (n = 190). For all GGE patients (incl. JME), the estimated risk of clinically relevant seizure aggravation under treatment with lamotrigine was 3.7 % (1.8 % for zonisamide and 0.8 % for levetiracetam). In conclusion, clinical significant aggravation of seizure frequency is common in lamotrigine-treated JME patients but rare in patients with other GGE subsyndromes or under treatment with other recommended anti-seizure medication.

Copyright © 2021 Elsevier B.V. All rights reserved.

Keywords: Juvenile myoclonic epilepsy; Lamotrigine; Myoclonus; Paradoxical reaction

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