Pharmacotherapy for Dravet Syndrome

Abstract

Dravet syndrome (DS) is an intractable pediatric epilepsy syndrome, starting in early childhood. This disorder typically manifests with febrile status epilepticus, and progresses to a multifocal epilepsy with febrile and non-febrile seizures with encephalopathy. Most cases are due to a mutation in the SCN1A gene. This article reviews treatments for DS, with an emphasis on pharmacotherapy. While many medications are used in treating the seizures associated with DS, these patients typically have medically refractory epilepsy, and polytherapy is often required. First-line agents include valproate and clobazam, although there are supportive data for topiramate, levetiracetam, stiripentol and the ketogenic diet. Other agents such as fenfluramine are promising therapies for Dravet syndrome. Sodium channel-blocking anticonvulsants such as carbamazepine and lamotrigine are generally contraindicated in this syndrome. Nonpharmacologic therapies (such as neurostimulation or surgery) are understudied in DS. Because DS is a global encephalopathy, pharmacologic treatment of non-epileptic manifestations of the disease is often necessary. Attention-deficit hyperactivity disorder is often encountered in patients with DS, and psychostimulants can be helpful for this indication. Other psychoactive drugs are less studied in this context. Extrapyramidal and gait disorders are often encountered in DS as well. While DS is a severe epileptic encephalopathy with a high (up to 15 %) mortality rate in childhood, careful pharmacologic management can improve these patients' clinical picture and quality of life.

Screening of conventional anticonvulsants in a genetic mouse model of epilepsy

“…). This analysis is consistent with what has been reported in the literature from other epilepsy centers …”

“…Dravet syndrome also includes developmental delays, cognitive impairment, motor dysfunction, and an increased risk for sudden unexpected death in epilepsy (SUDEP) . Typical pharmacotherapies include benzodiazepines, valproic acid, and stiripentol, but response is usually suboptimal . Lamotrigine and carbamazepine, both sodium channel inhibitors, are not recommended for Dravet syndrome as they have been reported to exacerbate seizures …”

Coadministered cannabidiol and clobazam: Preclinical evidence for both pharmacodynamic and pharmacokinetic interactions

“…[26][27][28] CBD has been shown to attenuate seizures in a mouse model of Dravet syndrome and reduce seizure frequency and severity in various acute seizure models. [26][27][28] CBD has been shown to attenuate seizures in a mouse model of Dravet syndrome and reduce seizure frequency and severity in various acute seizure models.…”

“…There is an urgent need to introduce better treatment options for intractable epilepsies, particularly for Dravet syndrome, since less than 30% of patients respond to first-line treatments. [26][27][28] CBD has been shown to attenuate seizures in a mouse model of Dravet syndrome and reduce seizure frequency and severity in various acute seizure models. [29][30][31][32][33] Following several successful Phase III trials, CBD has been approved by the FDA and offers a novel therapeutic option for patients with Dravet syndrome.…”

Epilepsy Caused by Pcdh19 Gene Mutation: A Review of Literature and the Authors’ Observations

“…По мнению A. Wallace и соавт. (2016), препаратами первого выбора в лечении син-дрома Драве следует считать вальпроаты и клобазам (не зарегистрирован в РФ), хотя также могут быть эффективны топирамат, леветирацетам, стирипентол (не зарегистрирован в РФ) в комбинированной те-рапии и кетогенная диета [22]. В соответствии с от-четом рабочей группы комиссии ILAE по педиатрии (2015) высокий доказательный уровень эффективно-сти при синдроме Драве имеет стирипентол (в соче-тании с вальпроатами и клобазамом); топирамат, зонисамид, вальпроат, бромиды и кетогенная диета «возможно эффективны» на низком доказательном уровне.…”