What is the drug of choice for absence seizures in a teenage girl?

Drug of Choice for Absence Seizures in Teenage Girls

Ethosuximide is the optimal first-line monotherapy for absence seizures in teenage girls, offering superior efficacy and tolerability compared to alternatives, though valproate should be preferred if generalized tonic-clonic seizures coexist. 1, 2

Primary Treatment Recommendation

• Ethosuximide represents the drug of choice for pure absence (petit mal) epilepsy in adolescent females, as it is FDA-indicated specifically for controlling absence seizures and demonstrates the highest freedom-from-failure rates. 1, 2

• A large randomized controlled trial in children with newly diagnosed childhood absence epilepsy found that ethosuximide and valproic acid had similar and superior freedom-from-failure rates at 12 months compared to lamotrigine, with ethosuximide having fewer intolerable adverse events than valproate. 2

• Ethosuximide controls approximately 70% of absence seizures and has a more favorable side effect profile than valproate, making it particularly appropriate for teenage girls of childbearing potential. 3

Critical Consideration for Teenage Girls

• Valproate carries significant teratogenicity risks and causes weight gain, making it potentially unacceptable in young women of childbearing age despite its equal efficacy to ethosuximide. 4, 2

• If the patient has both absence seizures AND generalized tonic-clonic seizures, valproate should be the preferred initial choice, as ethosuximide is ineffective against tonic-clonic seizures. 2, 3

Alternative and Second-Line Options

• Lamotrigine is less effective than both ethosuximide and valproate for absence seizures, with significantly higher treatment failure rates due to lack of seizure control, though it may be considered if the first two options fail. 2

• Lamotrigine controls only 50-60% of absences and GTCS, and commonly causes skin rashes, making it a third-line option. 3

Treatment Algorithm

For pure absence seizures in teenage girls:

1. Start with ethosuximide as first-line monotherapy 2, 3
2. If ethosuximide fails, switch to valproate (accepting teratogenicity counseling) 2
3. If both fail individually, consider lamotrigine 2
4. For resistant cases, combine low-dose lamotrigine with valproate, which may have dramatic beneficial effects 3

If absence seizures coexist with generalized tonic-clonic seizures:

1. Start with valproate as first-line (covers both seizure types) 2, 3
2. Consider lamotrigine as alternative if valproate is refused due to side effects 3
3. Add ethosuximide to either if absences remain uncontrolled 3

Important Caveats

• Carbamazepine and vigabatrin should be avoided as they can worsen absence and myoclonic seizures. 5, 4

• Approximately 90% of untreated patients with absence seizures respond to hyperventilation testing, which can be used diagnostically and to monitor treatment response. 3

• Typical absence status epilepticus occurs in about 30% of patients with absence epilepsy, requiring awareness and appropriate emergency management. 3

• The mechanism of ethosuximide involves reducing low threshold T-type calcium currents in thalamic neurons, which are critical to the thalamocortical circuitry generating spike-and-wave discharges characteristic of absence seizures. 6