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Anticonvulsant Agents: Stiripentol

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NeuroPsychopharmacotherapy

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Abstract

Stiripentol is a second-generation antiseizure medication indicated as adjunctive therapy (mainly with clobazam) for Dravet syndrome, a rare, severe, and drug-resistant epilepsy of early onset (first year of life). It is a GABAergic drug, which acts directly on the GABA(A) receptor via a different mechanism than benzodiazepines and with a pharmacodynamic interaction that potentiates the combination of the two. Stiripentol is also an inhibitor of CYP450 (primarily CYP3A4 and CYP2C19) with clinically meaningful pharmacokinetic interactions with comedications. Due to nonlinear kinetics its optimal maintenance dose decreases from 50 to 25 mg/kg/day from infancy to adulthood. Stiripentol has demonstrated its efficacy in two randomized controlled trials versus placebo dedicated to children with Dravet syndrome in addition to clobazam and valproate. Numerous observational studies have confirmed the maintenance of efficacy at long-term, with more than 20 years of follow-up, including in patients now adults. Tolerability has been studied in about a thousand patients of all ages. The main adverse effects are drowsiness and decreased appetite, most often related to overdosage in clobazam and valproate, which are alleviated by adjusting the dose of these comedications. Stiripentol remained the only drug approved for Dravet syndrome (since 2007 in Europe) until 2018 with the arrival of cannabidiol and then fenfluramine. In this context, two remarkable specificities of the efficacy of stiripentol should be noted, on the one hand in very young patients (less than 2 years old) and on the other hand over seizure duration (less status epilepticus).

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Authors and Affiliations

  1. Neuropediatric Department, Necker-Enfants Malades Hospital, Paris, France

    Catherine Chiron

Authors
  1. Catherine Chiron
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Correspondence to Catherine Chiron .

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Editors and Affiliations

  1. Dept Psychiatry , Psychosomatics & Psychotherapy, University of Würzburg, Medical School Clinical Neurochemistry, Würzburg, Germany

    Peter Riederer

  2. Inst für Psychologische Medizin, Haag, Bayern, Germany

    Gerd Laux

  3. Fujita Health University School Medicine, Toyoake, Aichi, Japan

    Toshiharu Nagatsu

  4. Center Translational Res Neurol Diseases, Dalian Med Uni Shanghai Inst Health Sc Center Translational Res Neurol Diseases, Dalian, China

    Weidong Le

  5. Würzburg, Bayern, Germany

    Christian Riederer

Section Editor information

  1. Beta Neurology – Competence Center for Epilepsy, Beta Klinik GmbH, Bonn, Germany

    Christian E. Elger

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Chiron, C. (2021). Anticonvulsant Agents: Stiripentol. In: Riederer, P., Laux, G., Nagatsu, T., Le, W., Riederer, C. (eds) NeuroPsychopharmacotherapy. Springer, Cham. https://doi.org/10.1007/978-3-319-56015-1_296-1

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  • DOI: https://doi.org/10.1007/978-3-319-56015-1_296-1

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-56015-1

  • Online ISBN: 978-3-319-56015-1

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