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The pharmacologic treatment of Dravet syndrome
Author(s) -
Chiron Catherine,
Dulac Olivier
Publication year - 2011
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/j.1528-1167.2011.03007.x
Subject(s) - clobazam , dravet syndrome , medicine , carbamazepine , levetiracetam , topiramate , lamotrigine , pharmacology , status epilepticus , adjunctive treatment , anesthesia , clonazepam , epilepsy , zonisamide , psychiatry
Summary Dravet syndrome (DS) is one of the most pharmacoresistant epilepsy syndromes. Valproate is used as a first‐line agent to prevent the recurrence of febrile seizures and oral/nasal/rectal benzodiazepine is used for any long‐lasting seizures, but these agents are most often insufficient. Lamotrigine, carbamazepine, and high doses of intravenous phenobarbital should be avoided because they may worsen seizures. Topiramate, levetiracetam, bromide, and the ketogenic diet may provide substantial efficacy as adjunctive therapy/procedure. Stiripentol is the only compound that proved its efficacy in DS through two independent randomized placebo‐controlled trials, when combined with valproate and clobazam. Their dose has to be decreased to minimize the side effects (mostly loss of appetite) resulting from pharmacokinetic interactions of stiripentol powerfully inhibiting cytochromes P450. Stiripentol acts as a γ‐aminobutyric acid (GABA)ergic agent, mainly via the α3 subunit of GABA A receptors. Stiripentol (Diacomit) was approved as an orphan drug in 2007 in Europe for adjunctive therapy in DS. Up to now, >500 children have been safely treated, and recent experiment in Japan confirmed stiripentol benefit in DS children with comedications other than valproate and clobazam. Because early status epilepticus is likely to negatively impact cognitive outcome, we recommend the introduction of stiripentol as soon as the diagnosis of DS is clinically confirmed. Topiramate and the ketogenic diet are alternatives in pharmacoresistant cases.