Stiripentol and vigabatrin current roles in the treatment of epilepsy |
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Authors: | Catherine Chiron |
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Institution: | 1. INSERM U1129, Neuropediatric Department, Necker Enfants-Malades Hospital, Paris, Francecatherine.chiron@aphp.fr |
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Abstract: | Introduction: Stiripentol and vigabatrin are the two anticonvulsant drugs currently approved in severe infantile-onset epilepsies, respectively Dravet syndrome and infantile spasms.Areas covered: For both, the indication was discovered by chance thanks to an exploratory study. Both demonstrated indisputable efficacy through randomized-controlled trials. Stiripentol as adjunctive therapy to clobazam and valproate performed better than placebo, and vigabatrin as first-line monotherapy better than the reference steroid therapy in spasms due to tuberous sclerosis. At one-year treatment vigabatrin and steroids were equally efficient in the other etiologies of spasms. However, it took more than 20 years for both drugs to be approved world-wide.Expert opinion: Stiripentol suffered from pharmacokinetic potentiation of clobazam, thus raising the question whether it was efficient per se. Finally, animal models and pharmacogenetic data on CYP2C19 confirmed its specific anticonvulsant effect. Stiripentol (in comedication with clobazam and valproate) is therefore to be recommended for Dravet patients. Vigabatrin was found to have a frequent and irreversible retinal toxicity, which required an alternative visual testing to be detected in young children. Today the benefit/risk ratio of vigabatrin as first-line is considered to be positive in infantile spasms, given the severity of this epilepsy and the lack of a safer alternative therapy. |
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Keywords: | Antiepileptic drug trials clobazam CYP2C19 drug-drug interactions dravet syndrome Electroretinogram infantile spasms stiripentol vigabatrin visual field loss |
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