What is the recommended treatment for acute prevention of absence seizures?

Acute Prevention of Absence Seizures

For acute prevention of absence seizures, initiate ethosuximide as first-line monotherapy at 15 mg/kg/day (up to 250 mg initially), increasing by 5-10 mg/kg/week until seizures are controlled, with valproic acid as an alternative when generalized tonic-clonic seizures coexist. 1, 2, 3

First-Line Treatment Selection

Ethosuximide is the preferred initial agent for absence seizures only, controlling approximately 70% of typical absence seizures with the best tolerability profile. 3 The FDA-approved dosing begins at 15 mg/kg/day, titrating upward at weekly intervals by 5-10 mg/kg/day until seizure control is achieved or side effects emerge. 2 Therapeutic serum concentrations range from 50-100 mcg/mL for most patients. 1

Critical Limitation of Ethosuximide

• Ethosuximide is unsuitable as monotherapy if generalized tonic-clonic seizures (GTCS) coexist, as it lacks efficacy against these seizure types. 3 This is a common pitfall—always assess for other seizure types before selecting ethosuximide alone.

Alternative First-Line Options

Valproic acid controls 75% of absence seizures and additionally treats GTCS (70%) and myoclonic jerks (75%), making it superior when multiple seizure types are present. 3 FDA dosing for absence seizures starts at 15 mg/kg/day, increasing at weekly intervals by 5-10 mg/kg/day, with a maximum recommended dose of 60 mg/kg/day. 1 Therapeutic levels are 50-100 mcg/mL. 1

Valproic Acid Considerations

• Thrombocytopenia risk increases significantly at trough levels above 110 mcg/mL in females and 135 mcg/mL in males—monitor complete blood counts regularly. 1
• May be undesirable for women of childbearing potential due to teratogenic risks. 3
• Dose-related adverse effects including elevated liver enzymes require monitoring. 1

Lamotrigine controls 50-60% of absence seizures and GTCS but is less effective than ethosuximide or valproic acid for absence seizures specifically. 3 It carries a significant risk of skin rashes and may worsen myoclonic jerks. 3

Refractory Cases

For resistant absence seizures, combination therapy is required in the majority of patients. 4 The most effective combinations include:

• Low-dose lamotrigine added to valproic acid may produce dramatic beneficial effects in treatment-resistant cases. 3
• Ethosuximide combined with valproic acid for patients with both absence and GTCS. 3
• Clonazepam as adjunctive therapy, particularly effective for absences with myoclonic components. 3
• Acetazolamide may serve as an additional adjunctive agent. 3

Special Population: Atypical Absence Seizures

Atypical absence seizures are typically intractable and require polytherapy, though with limited efficacy. 4 These occur in developmental and epileptic encephalopathies and differ fundamentally from typical childhood absence epilepsy. 4 The same first-line agents apply (ethosuximide, valproic acid, lamotrigine), but expectations for seizure freedom should be tempered. 4

Dosing Algorithm for Typical Absence Seizures

Ethosuximide Monotherapy (absence seizures only):

• Start: 15 mg/kg/day (250 mg if weight 10-24.9 kg). 1, 2
• Titrate: Increase by 5-10 mg/kg/week. 2
• Maximum: 60 mg/kg/day. 1
• Target levels: 50-100 mcg/mL. 1

Valproic Acid Monotherapy (absence + other generalized seizures):

• Start: 15 mg/kg/day. 1
• Titrate: Increase by 5-10 mg/kg/week. 1
• Maximum: 60 mg/kg/day. 1
• Target levels: 50-100 mcg/mL. 1
• Monitor for thrombocytopenia at levels >110 mcg/mL (females) or >135 mcg/mL (males). 1

Common Pitfalls to Avoid

• Do not use levetiracetam for absence seizures—it is not indicated and lacks efficacy for this seizure type. 5, 6
• Avoid carbamazepine, phenytoin, and other sodium channel blockers, as these may worsen absence seizures. 3
• Do not abruptly discontinue antiepileptic drugs due to risk of precipitating status epilepticus. 1
• In elderly patients, start at lower doses and titrate more slowly due to decreased clearance and increased sensitivity to somnolence. 1

Monitoring Requirements

• Baseline and periodic liver function tests (valproic acid). 1
• Complete blood counts to monitor for thrombocytopenia (valproic acid). 1
• Serum drug levels when seizure control is inadequate or toxicity suspected. 1
• EEG with hyperventilation to confirm seizure control, as clinical absence may be subtle or unrecognized. 7, 3