Initial Management of Dravet Syndrome
The initial management for patients with Dravet Syndrome should include valproate as first-line therapy, with clobazam as an adjunctive treatment, followed by stiripentol when seizures remain uncontrolled. 1, 2, 3, 4
First-Line Therapy
Valproate (VPA): Should be initiated at the first onset of complicated febrile seizures in Dravet syndrome patients
- Mechanism: Broad-spectrum anti-seizure medication
- Efficacy: Helps prevent recurrence of febrile seizures but is usually insufficient as monotherapy
- Monitoring: Regular liver function tests, complete blood count, and drug levels
Clobazam: Add as second-line therapy when valproate alone is insufficient
- Mechanism: Benzodiazepine that enhances GABA inhibitory effects
- Dosing: Start low and titrate based on clinical response
- Side effects: Somnolence, ataxia, behavioral changes
Second-Line Therapy
- Stiripentol (Diacomit): Add when seizures remain uncontrolled on valproate and clobazam
- FDA-approved specifically for Dravet syndrome 1
- Mechanism: Enhances GABAergic neurotransmission via the alpha-3 subunit of GABA(A) receptors 4
- Efficacy: Demonstrated in randomized controlled trials with 71% responder rate (defined as >50% reduction in seizure frequency) 1
- Dosing: 50mg/kg/day (up to 2500mg/day)
- Important note: When adding stiripentol, reduce doses of valproate and clobazam to minimize side effects due to cytochrome P450 inhibition 3, 4
Rescue Medication Plan
- Develop a home rescue plan for prolonged or clustered seizures
- Options include:
- Oral/nasal/rectal benzodiazepines for any long-lasting seizures 4
- Clear instructions for caregivers on when to administer rescue medication
- When to seek emergency care
Medications to Avoid
- Sodium channel agents should be strictly avoided as they typically worsen seizures in Dravet syndrome:
Alternative/Additional Therapies
If the above regimen is insufficient, consider:
Topiramate:
Ketogenic Diet:
- Consider as non-pharmacological adjunctive therapy
- Requires specialized nutritional support and monitoring
Levetiracetam:
- Can be considered as an alternative adjunctive therapy
- Less evidence for efficacy specifically in Dravet syndrome
Bromides:
- Used in some countries (particularly Germany and Japan) 5
- Limited evidence but reported efficacy in refractory cases
Monitoring and Follow-up
Regular monitoring of:
- Seizure frequency and type
- Medication side effects
- Growth parameters (height, weight)
- Complete blood count, liver function tests
- Drug levels when applicable
For patients on stiripentol:
Common Pitfalls to Avoid
- Delayed diagnosis and treatment: Early intervention is critical to potentially improve developmental outcomes
- Using sodium channel blockers: These can dramatically worsen seizures in Dravet syndrome
- Inadequate rescue medication planning: All patients need a clear emergency plan
- Failure to adjust concomitant medications: When adding stiripentol, doses of valproate and clobazam often need reduction
- Overlooking trigger avoidance: Counsel families to avoid common seizure triggers:
- Hyperthermia/fever (use antipyretics promptly)
- Flashing lights and patterns
- Excessive physical exertion
- Sleep deprivation
Holistic Care Considerations
- Dravet syndrome requires multidisciplinary care beyond seizure management:
- Developmental and cognitive assessment
- Physical, occupational, and speech therapy
- Behavioral support
- Family education and support resources
The evidence strongly supports early intervention with appropriate anti-seizure medications, with stiripentol being the only medication specifically proven effective in randomized controlled trials for Dravet syndrome when combined with valproate and clobazam 1, 4.