Treatment of Absence Seizures in Pediatric Patients
Ethosuximide is the optimal first-line monotherapy for pediatric patients with typical absence seizures, offering superior efficacy (70% seizure freedom at 12 months) and fewer attentional side effects compared to valproate and lamotrigine. 1
First-Line Treatment Selection
For absence seizures alone (without generalized tonic-clonic seizures):
- Ethosuximide should be initiated at 250 mg/day for children 3-6 years old, or 500 mg/day for children ≥6 years old 2
- Increase by 250 mg every 4-7 days until seizure control is achieved with minimal side effects 2
- The optimal dose for most pediatric patients is 20 mg/kg/day, targeting plasma levels of 40-100 mcg/mL 2
- Maximum dose is 1.5 g daily in divided doses 2
For absence seizures coexisting with generalized tonic-clonic seizures:
- Valproate should be preferred over ethosuximide, as ethosuximide is ineffective against tonic-clonic seizures 3
- Initiate valproate at 10-15 mg/kg/day and increase by 5-10 mg/kg/week 4
- Target therapeutic plasma levels of 50-100 mcg/mL 4
- Optimal clinical response is typically achieved at doses below 60 mg/kg/day 4
Comparative Efficacy Evidence
The landmark randomized controlled trial in 453 children with newly diagnosed childhood absence epilepsy demonstrated clear efficacy differences 1:
- Ethosuximide: 45% seizure freedom at 16 weeks 1
- Valproate: 44% seizure freedom at 16 weeks (not significantly different from ethosuximide) 1
- Lamotrigine: 21% seizure freedom at 16 weeks (significantly inferior to both ethosuximide and valproate, P<0.001) 1
Critical Tolerability Considerations
Ethosuximide demonstrates superior neuropsychological tolerability:
- Attentional dysfunction occurred in 33% of children on ethosuximide versus 49% on valproate (P=0.03) 1
- Treatment discontinuation rates due to adverse events were similar across all three drugs 1
Valproate carries specific warnings:
- Higher frequency of adverse events (33% treatment failures) compared to ethosuximide (25%) and lamotrigine (20%) 1
- Should be avoided in women of childbearing potential due to teratogenicity and neurodevelopmental risks 5
Treatment Algorithm
Step 1: Determine seizure types present
- If absence seizures only → Start ethosuximide 1, 3
- If absence + generalized tonic-clonic seizures → Start valproate 3
Step 2: Titrate to therapeutic dose
- Ethosuximide: Target 20 mg/kg/day with plasma levels 40-100 mcg/mL 2
- Valproate: Target 10-15 mg/kg/day initially, increase to 50-100 mcg/mL plasma level 4
Step 3: If monotherapy fails after adequate trial
- Consider combination therapy with ethosuximide + valproate 5
- Low-dose lamotrigine added to valproate may provide dramatic benefit in resistant cases 5
- Clonazepam may be useful for absences with myoclonic components 5
Common Pitfalls to Avoid
Do not use lamotrigine as first-line monotherapy - it demonstrates significantly lower efficacy (21% vs 45% seizure freedom) and requires prolonged titration 1
Do not assume all absence seizures are the same - atypical absence seizures (seen in developmental epileptic encephalopathies) are usually intractable and require different management approaches 6
Do not prescribe ethosuximide for patients with both absence and tonic-clonic seizures - ethosuximide is ineffective against generalized tonic-clonic seizures 3
Monitor for attentional side effects with valproate - nearly 50% of children experience attentional dysfunction, which may impact school performance 1
Speed of Response
Valproate demonstrates faster onset of action compared to lamotrigine 7:
- At 1 month: 52.6% seizure freedom with valproate vs 5.3% with lamotrigine (P=0.004) 7
- At 3 months: 63.1% with valproate vs 36.8% with lamotrigine 7
- This faster response is partly due to shorter titration requirements for valproate 7
Monitoring Requirements
For ethosuximide:
- Plasma levels should be checked if seizure control is inadequate at 20 mg/kg/day 2
- Target therapeutic range: 40-100 mcg/mL 2
For valproate: