Management of Absence Seizures
First-Line Treatment Recommendation
Valproate is the definitive first-line treatment for absence seizures, controlling seizures in approximately 75% of patients, with ethosuximide as an equally effective alternative specifically for absence seizures when other generalized seizure types are not present. 1, 2, 3
Treatment Algorithm
Initial Monotherapy Selection
For typical absence seizures:
Valproate is the drug of choice for idiopathic generalized epilepsies with absence seizures, particularly when other generalized seizure types (tonic-clonic, myoclonic) coexist, as it controls absences in 75% of patients, generalized tonic-clonic seizures in 70%, and myoclonic jerks in 75%. 3, 4
Ethosuximide is equally effective, controlling 70% of absence seizures, but is unsuitable as monotherapy if other generalized seizures coexist, as it only suppresses the paroxysmal three cycle per second spike and wave activity specific to absence seizures. 5, 3
Lamotrigine may control absences in 50-60% of patients and is a suitable alternative for women of childbearing potential due to lower teratogenic risk compared to valproate, though it shows slower onset of action and may worsen myoclonic jerks. 1, 3, 6
Comparative Efficacy Data
A head-to-head randomized trial demonstrated that valproate achieves seizure freedom significantly faster than lamotrigine: 52.6% seizure-free at 1 month with valproate versus only 5.3% with lamotrigine (p=0.004), though by 12 months the difference narrowed (68% vs 53%). 7 This faster onset with valproate is clinically important for rapidly controlling disabling absence seizures that can occur hundreds of times daily.
Special Population Considerations
Women of childbearing potential:
- Avoid valproate due to significantly increased risks of fetal malformations and neurodevelopmental delay. 1
- Use lamotrigine or levetiracetam as first-line alternatives instead. 1
- If valproate must be used, explicit discussion of teratogenic risks and contraceptive measures is mandatory. 1
Second-Line and Combination Therapy
When monotherapy fails:
Combination therapy with any two of the three first-line drugs (valproate, ethosuximide, lamotrigine) may be needed for resistant cases. 3
Low-dose lamotrigine added to valproate may have a dramatic beneficial effect in refractory absence seizures. 3
Clonazepam is useful as an adjunctive drug, particularly in absences with myoclonic components. 3
Acetazolamide may serve as another adjunctive option. 3
Dosing Guidelines
Valproate:
- Start at 10 mg/kg/day in divided doses
- Increase by 5 mg/kg every 3 days as needed
- Target dose: 20-30 mg/kg/day (maximum 30 mg/kg/day)
- Target serum level: 50-100 mg/L 7
Lamotrigine:
- Start at 0.5 mg/kg/day for 2 weeks
- Increase to 1.0 mg/kg/day for 2 weeks
- Then increase by 1 mg/kg/day every 5 days
- Target dose: 2-12 mg/kg/day 7
Critical Pitfalls to Avoid
Never use carbamazepine, phenytoin, or other sodium channel blockers as they can worsen absence seizures. 1
Never use phenobarbital as first-line treatment, as it performs significantly worse than other options for absence seizures. 1
Never prescribe valproate to women of childbearing potential without explicit contraceptive counseling and documentation of teratogenic risk discussion. 1
Do not use ethosuximide as monotherapy if the patient has or may develop other generalized seizure types (tonic-clonic, myoclonic), as it is ineffective against these. 3
Monitoring and Follow-Up
- Confirm diagnosis with video-EEG showing characteristic 3-4 Hz generalized spike-and-wave discharges. 3
- Hyperventilation during EEG precipitates absences in ~90% of untreated patients, aiding diagnosis. 3
- Monitor for complete seizure control, as absence seizures can be subtle and patients may not report them. 1
- Assess for associated seizure types that may require broader-spectrum therapy. 3