title: Stiripentol and vigabatrin current roles in the treatment of epilepsy.
abstract: BACKGROUND
  Stiripentol and vigabatrin are the two anticonvulsant drugs currently approved in severe infantile-onset epilepsies, respectively Dravet syndrome and infantile spasms.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: a INSERM U1129, Neuropediatric Department , Necker Enfants-Malades Hospital , Paris , France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Chiron
mesh_terms: D000927:Anticonvulsants / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003131:Combined Modality Therapy / Q000379:methods*; D004148:Dioxolanes / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004827:Epilepsy / Q000188:drug therapy*; D006801:Humans; D007223:Infant; D016896:Treatment Outcome; D020888:Vigabatrin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000927:Anticonvulsants; D004148:Dioxolanes; D020888:Vigabatrin; C021092:stiripentol
keywords: Antiepileptic drug trials; CYP2C19; Electroretinogram; clobazam; dravet syndrome; drug-drug interactions; infantile spasms; stiripentol; vigabatrin; visual field loss