What is the initial treatment for absence seizures?

Initial Treatment for Absence Seizures

Ethosuximide is the first-line treatment for typical absence seizures in children and adolescents due to its superior efficacy and tolerability profile compared to other options. 1

Medication Selection Algorithm

First-line therapy:

• Ethosuximide
  • Efficacy: Controls approximately 70% of absence seizures 2
  • Dosing: Initial dose 15 mg/kg/day, increasing at weekly intervals by 5-10 mg/kg/day until seizures are controlled or side effects occur 3
  • Maximum recommended dose: 40 mg/kg/day for 50% probability of seizure freedom; 55 mg/kg/day for 75% probability 4
  • Target plasma concentration: 40-100 μg/mL 5

Alternative first-line options:

• Valproic acid

  • Indicated when absence seizures coexist with other generalized seizure types (e.g., myoclonic jerks, generalized tonic-clonic seizures) 1
  • Efficacy: Controls approximately 75% of absence seizures 2
  • Dosing: Initial dose 15 mg/kg/day, increasing at weekly intervals by 5-10 mg/kg/day 3
  • Maximum recommended dose: 60 mg/kg/day 3
  • Target plasma concentration: 50-100 μg/mL 3
  • Caution: Higher rate of adverse events (33%) compared to ethosuximide (25%) 1

• Lamotrigine

  • Efficacy: Controls approximately 50-60% of absence seizures 2
  • Less effective than ethosuximide or valproate (21% seizure freedom at 12 months vs. 45% for ethosuximide) 1
  • May worsen myoclonic jerks 2
  • Skin rashes are common 2

Evidence-Based Treatment Decision Making

The choice of initial therapy should be guided by:

1. Seizure type specificity:

   • For pure absence seizures: Ethosuximide is preferred due to superior efficacy and tolerability 1
   • For absence seizures with coexisting generalized tonic-clonic seizures: Valproate is preferred as ethosuximide is ineffective against tonic-clonic seizures 1

2. Patient characteristics:

   • For females of childbearing potential: Consider ethosuximide or lamotrigine over valproate due to teratogenic risks 6
   • For patients with behavioral issues: Avoid lamotrigine which may worsen myoclonic jerks 2

3. Syndrome classification:

   • Typical absence seizures: Ethosuximide, valproate, or lamotrigine 2
   • Atypical absence seizures (usually in developmental epileptic encephalopathies): Often require polytherapy with limited efficacy 7

Monitoring and Follow-up

• EEG with sleep recording at diagnosis and follow-up EEG every 3-6 months 6
• Monitor drug levels to ensure therapeutic range (ethosuximide: 40-100 μg/mL; valproate: 50-100 μg/mL) 3, 5
• Assess for adverse effects:
  • Ethosuximide: Generally well-tolerated with minor side effects 5
  • Valproate: Gastrointestinal disturbances, somnolence, tremor 6
  • Lamotrigine: Skin rash (requires slow titration) 6

Treatment Resistance Management

If initial monotherapy fails:

1. Optimize dose to maximum tolerated level within therapeutic range
2. Switch to alternative monotherapy
3. Consider combination therapy:
   • Valproic acid + ethosuximide
   • Low doses of lamotrigine added to valproic acid may have dramatic beneficial effects 2
   • Clonazepam may be useful as adjunctive therapy, particularly for absences with myoclonic components 2

Key Pitfalls to Avoid

1. Misdiagnosis: Ensure proper diagnosis with video-EEG confirmation, as treatment differs significantly between typical and atypical absence seizures 7

2. Inappropriate medication selection: Avoid using medications ineffective for absence seizures or those that may worsen seizures (e.g., carbamazepine)

3. Inadequate dosing: Ensure therapeutic drug levels are achieved before declaring treatment failure

4. Overlooking comorbid seizure types: Assess for other seizure types that may require broader spectrum antiepileptic coverage

5. Failure to consider adverse effects: Balance seizure control with medication tolerability, especially in children where cognitive effects are important 5

The high-quality evidence from a large randomized controlled trial demonstrates that ethosuximide is the optimal initial monotherapy for children with absence seizures, with valproate being equally effective but having more adverse effects 1.