What is the initial management for patients with Dravet syndrome?

Initial Management of Dravet Syndrome

The initial management of Dravet syndrome should include valproate as first-line therapy, followed by the addition of clobazam and stiripentol when seizures persist, with careful avoidance of sodium channel agents that can worsen seizures. 1, 2, 3

First-Line Pharmacological Management

Valproate

• Should be initiated at the first onset of complicated febrile seizures in patients with suspected or confirmed Dravet syndrome
• Serves as the foundation of treatment to prevent recurrence of febrile seizures
• Dosing should be individualized based on patient weight and response

Benzodiazepines

• Oral/nasal/rectal benzodiazepines should be prescribed for acute management of prolonged seizures
• Clobazam is recommended as a second agent when valproate alone is insufficient
• Families must be trained on proper administration of rescue benzodiazepines

Second-Line Therapy

Stiripentol (Diacomit)

• Add when seizures persist despite valproate and clobazam
• Only medication with proven efficacy in two independent randomized placebo-controlled trials 4, 2
• FDA-approved specifically for Dravet syndrome
• Dosing: 50mg/kg/day (maximum 2500mg/day)
• Significantly reduces frequency of generalized clonic or tonic-clonic seizures:
  • 71% responder rate in Study 1
  • 67% responder rate in Study 2 4
• When adding stiripentol, doses of valproate and clobazam should be reduced to minimize side effects from drug interactions 2, 3

Medications to Avoid

• Sodium channel agents must be strictly avoided as they typically worsen seizures:
  • Carbamazepine
  • Oxcarbazepine
  • Phenytoin
  • Lamotrigine 1, 2, 3

Alternative or Additional Therapies

For patients with inadequate response to first- and second-line therapies:

1. Topiramate

   • Effective adjunctive therapy for refractory seizures in Dravet syndrome

2. Ketogenic Diet

   • Consider as non-pharmacological option for drug-resistant cases

3. Levetiracetam

   • May provide benefit as an adjunctive therapy

4. Bromides

   • Used in some countries (particularly Germany and Japan) with anecdotal evidence of efficacy 5

Seizure Prevention and Management

Seizure Rescue Protocol

• All patients need a personalized status epilepticus protocol
• Home rescue medication (typically benzodiazepines) must be readily available
• Families should be educated on when and how to administer rescue medications
• Clear instructions for when to seek emergency care

Trigger Avoidance

• Counsel families on avoiding common seizure triggers:
  • Hyperthermia (fever, hot baths)
  • Flashing lights and patterns
  • Sleep deprivation
  • Excessive physical exertion

Monitoring and Follow-up

• Regular monitoring of:

  • Seizure frequency and type
  • Medication side effects
  • Growth parameters
  • Liver function tests
  • Complete blood count (especially with stiripentol)

• Dose adjustments may be necessary to balance seizure control and side effects

• "Start low, go slow" approach recommended for medication titration 5

Multidisciplinary Care

Beyond seizure management, comprehensive care should include:

• Neuropsychological assessment
• Physical, occupational, and speech therapy
• Behavioral support
• Social work services

Early and aggressive treatment is critical as recurrent seizures and status epilepticus can negatively impact cognitive outcomes 2. The goal of therapy is to reduce seizure burden while minimizing medication side effects to optimize quality of life and developmental outcomes.