What is the initial treatment for absence seizures, particularly in children?

Initial Treatment for Absence Seizures in Children

Ethosuximide is the optimal initial monotherapy for children with typical absence seizures due to its superior efficacy and favorable side effect profile compared to other options. 1

Understanding Absence Seizures

Absence seizures are brief epileptic seizures characterized by:

• Sudden loss of awareness
• Typical EEG showing generalized 3-4 Hz spike/polyspike and slow wave discharges
• Duration of seconds (typically 2-30 seconds)
• Often precipitated by hyperventilation (in 90% of untreated patients)
• Usually starting in childhood or adolescence

First-Line Treatment Options

Ethosuximide

• Dosing: Initial dose of 15 mg/kg/day, increasing at one-week intervals by 5-10 mg/kg/day until seizures are controlled 2
• Maximum recommended dose: 60 mg/kg/day 2
• Therapeutic serum concentration: 50-100 μg/mL 2
• Efficacy: Controls approximately 70% of absence seizures 3
• Mechanism: Reduces low threshold T-type Ca²⁺ currents in thalamic neurons, decreases persistent Na⁺ and Ca²⁺-activated K⁺ currents 4

Valproic Acid

• Dosing: Initial dose of 10-15 mg/kg/day, increasing by 5-10 mg/kg/week 2
• Optimal clinical response: Usually achieved at doses below 60 mg/kg/day 2
• Efficacy: Controls absences in 75% of patients, also effective for GTCS (70%) and myoclonic jerks (75%) 3
• Caution: Higher proportion of adverse events (33%) compared to ethosuximide (25%) 1

Lamotrigine

• Efficacy: Controls approximately 50-60% of absences 3
• Limitations: Significantly lower seizure freedom rate (21%) compared to ethosuximide (45%) or valproate (44%) at 12 months 1
• Caution: May worsen myoclonic jerks; skin rashes are common 3

Evidence-Based Treatment Algorithm

1. First-line therapy: Ethosuximide monotherapy

   • High-quality evidence from a large randomized controlled trial shows ethosuximide provides the best balance of efficacy (45% seizure freedom at 12 months) and tolerability 1

2. Alternative first-line option: Valproic acid

   • Consider when absence seizures coexist with generalized tonic-clonic seizures, as ethosuximide is ineffective for tonic-clonic seizures 1, 3
   • Similar efficacy to ethosuximide for absence seizures (44% seizure freedom) but higher rate of adverse events 1

3. Second-line therapy: Combination therapy

   • For resistant cases, consider combinations of ethosuximide, valproate, and lamotrigine 3
   • Low doses of lamotrigine added to valproate may be particularly effective 3

Special Considerations

• Coexisting seizure types: If absence and generalized tonic-clonic seizures occur together, valproate should be preferred over ethosuximide 1
• Female patients: Consider potential teratogenic effects of valproate in adolescent females of childbearing potential 3, 5
• Atypical absences: These are generally more difficult to treat and often require polytherapy 5
• Monitoring: Regular assessment of seizure frequency, medication adherence, and EEG findings is essential 6

Common Pitfalls to Avoid

1. Misdiagnosis: Ensure proper diagnosis with EEG confirmation before initiating treatment
2. Inadequate dosing: Titrate medication to therapeutic levels before concluding treatment failure
3. Overlooking coexisting seizure types: Ethosuximide alone is insufficient if other seizure types are present
4. Ignoring adverse effects: Monitor for side effects, particularly gastrointestinal and CNS effects with ethosuximide

In conclusion, ethosuximide represents the optimal initial empirical monotherapy for children with absence seizures based on the best available evidence, offering the best balance of efficacy and tolerability.