What is the first line treatment for absence seizures?

First-Line Treatment for Absence Seizures

Ethosuximide is the first-line treatment for typical absence seizures in children and adolescents when absence seizures occur in isolation, based on superior efficacy and tolerability compared to other options. 1, 2, 3

Treatment Selection Algorithm

When Absence Seizures Occur Alone

• Ethosuximide should be initiated as first-line monotherapy for children with typical absence seizures (brief loss of awareness with 3 Hz spike-wave on EEG) when no other seizure types are present. 2, 3
• Ethosuximide controls approximately 70% of absence seizures and demonstrates optimal tolerability with the fewest adverse effects compared to valproate and lamotrigine. 3, 4
• The large randomized controlled trial comparing all three agents found that ethosuximide and valproate had similar freedom-from-failure rates at 12 months, both superior to lamotrigine, but ethosuximide had fewer intolerable adverse events than valproate. 3

When Absence and Generalized Tonic-Clonic Seizures Coexist

• Valproate should be preferred over ethosuximide when both absence and generalized tonic-clonic seizures are present, as ethosuximide is ineffective against tonic-clonic seizures. 1, 3, 4
• Valproate controls 75% of absence seizures, 70% of generalized tonic-clonic seizures, and 75% of myoclonic jerks when present. 4
• However, avoid valproate in women of childbearing potential due to significant teratogenic risks including fetal malformations and neurodevelopmental delay. 3, 5

Lamotrigine as Alternative First-Line

• Lamotrigine represents a third-line option when ethosuximide and valproate are contraindicated or not tolerated. 3, 4
• Lamotrigine controls approximately 50-60% of absence seizures, significantly less effective than ethosuximide or valproate. 3, 4
• The frequency of treatment failures due to lack of seizure control was significantly higher with lamotrigine compared to ethosuximide and valproate (P < 0.001). 3
• Lamotrigine may worsen myoclonic jerks if present and causes skin rashes in a substantial proportion of patients. 4, 6

Dosing Considerations

• Valproate demonstrates faster onset of action than lamotrigine, with 52.6% of patients seizure-free at 1 month versus only 5.3% with lamotrigine, though this difference narrows by 12 months. 6
• Ethosuximide suppresses the characteristic 3 Hz spike-wave activity by depressing motor cortex excitability and elevating the seizure threshold. 2

Common Pitfalls to Avoid

• Never use ethosuximide as monotherapy if generalized tonic-clonic seizures coexist with absences, as it provides no protection against tonic-clonic seizures. 3, 4
• Avoid valproate in young children due to hepatotoxicity risk, particularly in those under 2 years of age. 5
• Do not delay treatment while awaiting extensive workup—typical absence seizures with characteristic 3 Hz spike-wave on EEG and positive hyperventilation test (90% of untreated patients) can be diagnosed and treated promptly. 4

Drug-Resistant Cases

• When first-line monotherapy fails after adequate trial, combination therapy with ethosuximide plus valproate or low-dose lamotrigine added to valproate may be effective. 4, 5
• For truly refractory absence seizures, consider levetiracetam, topiramate, or zonisamide as second-line adjunctive agents. 5
• Clonazepam may be useful for absences with myoclonic components, and acetazolamide can serve as an adjunctive agent. 4