Stiripentol open study in Japanese patients with Dravet syndrome

Epilepsia. 2009 Nov;50(11):2362-8. doi: 10.1111/j.1528-1167.2009.02179.x. Epub 2009 Jun 22.

Abstract

Purpose: To survey the treatment situation of Dravet syndrome in Japan and to compare this result with effectiveness of stiripentol (STP) add-on therapy in an open-label multicenter study.

Methods: Medical records of patients with Dravet syndrome who visited the study institutions during 2006 were surveyed to examine the effect of antiepileptic drugs (AEDs) on clonic or tonic-clonic seizures (GTCS). Patients older than 1 year of age treated with at least one conventional AED and more than four GTCS per month were invited to participate in the STP study. Seizure status and adverse effects during the first 4 weeks of STP (50 or 1,000 mg/day) add-on therapy (early period) and during long-term treatment were compared with baseline.

Results: Only 15% of the treatment trials with 15 conventional AEDs in 112 patients succeeded in reducing seizures by more than 50%. With STP, GTCS were reduced more than 50% in 14 of 23 patients (61%), including 2 who became seizure-free, in the early period. Moreover, duration of seizures was shortened in 10 patients and status epilepticus decreased in 6. These effects continued in the long-term although to a lesser degree. Adverse effects (loss of appetite, sleep disturbance, ataxia, hyperactivity/irritability) disappeared after dose modification in most cases. STP was effective at a lower than initial dose in five patients. Some patients benefited from STP added on clobazam despite mutation in CYP2C19.

Conclusion: Our data suggest that an early introduction of STP into Japan will result in substantial patient benefit.

Publication types

  • Comparative Study
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Anticonvulsants / adverse effects
  • Anticonvulsants / therapeutic use*
  • Aryl Hydrocarbon Hydroxylases / genetics
  • Benzodiazepines / therapeutic use
  • Child
  • Child, Preschool
  • Clobazam
  • Cytochrome P-450 CYP2C19
  • Dioxolanes / adverse effects
  • Dioxolanes / therapeutic use*
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Epilepsies, Myoclonic / drug therapy*
  • Epilepsy, Tonic-Clonic / drug therapy*
  • Epilepsy, Tonic-Clonic / genetics
  • Female
  • Humans
  • Infant
  • Male
  • Medical Records
  • Middle Aged
  • Retrospective Studies
  • Syndrome
  • Treatment Outcome

Substances

  • Anticonvulsants
  • Dioxolanes
  • Benzodiazepines
  • Clobazam
  • Aryl Hydrocarbon Hydroxylases
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19
  • stiripentol