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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.

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Correspondence to Daniel L. Kenney-Jung.

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Drs. Kenney-Jung and Wallace have no disclosures. Dr. Wirrell is involved with clinical trials of cannabidiol (GW Pharma) and fenfluramine (Zogenix) and is a member of the Dravet Syndrome Foundation Steering Committee. She has also received Grant support from the Dravet Syndrome Foundation.

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Wallace, A., Wirrell, E. & Kenney-Jung, D.L. Pharmacotherapy for Dravet Syndrome. Pediatr Drugs 18, 197–208 (2016). https://doi.org/10.1007/s40272-016-0171-7

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  • DOI: https://doi.org/10.1007/s40272-016-0171-7

Keywords

  • Deep Brain Stimulation
  • Valproate
  • Status Epilepticus
  • Topiramate
  • GABAA Receptor