Management of Childhood Absence Epilepsy
Ethosuximide is the first-line treatment for childhood absence epilepsy (CAE) when only absence seizures are present, offering superior efficacy with fewer cognitive side effects compared to alternatives. 1, 2, 3
Initial Pharmacologic Management
First-Line Treatment: Ethosuximide
Ethosuximide should be initiated at 250 mg/day for children 3-6 years old and 500 mg/day for children ≥6 years old, with dose increases of 250 mg every 4-7 days until seizure control is achieved with minimal side effects 1
The optimal dose for most pediatric patients is 20 mg/kg/day, targeting plasma levels of 40-100 mcg/mL 1
Maximum daily dose is 1.5 g, administered in divided doses under strict physician supervision 1
Ethosuximide demonstrated 53% freedom-from-treatment-failure at 16 weeks, comparable to valproic acid (58%) but significantly superior to lamotrigine (29%) 2
Critically, ethosuximide causes significantly less attentional dysfunction (33%) compared to valproic acid (49%), making it the preferred choice when cognitive preservation is prioritized 2
Second-Line Treatment: Valproic Acid
Valproic acid should be reserved for patients who fail ethosuximide or when generalized tonic-clonic seizures coexist with absence seizures 2, 3, 4
While equally effective as ethosuximide for seizure control, valproic acid carries higher risk of adverse effects including attentional dysfunction, hepatotoxicity, and teratogenicity 2, 4
Third-Line Treatment: Lamotrigine
- Lamotrigine is significantly less effective than both ethosuximide and valproic acid (29% vs 53% and 58% freedom-from-failure respectively) and should only be considered after first-line options have failed 2, 3
Alternative Combination Therapy
Low-dose valproic acid-lamotrigine combination therapy showed superior freedom-from-treatment-failure rates at 48 months compared to monotherapy in one retrospective study, with the advantage of lower individual drug doses and potentially fewer side effects 5
This combination should be considered when monotherapy fails, though the evidence is less robust than for ethosuximide monotherapy 5
Treatment Duration and Monitoring
Mean treatment duration is typically 3-4 years, with most patients achieving seizure remission 6
EEG monitoring should track the disappearance of 3-Hz spike-and-wave complexes, as shorter interval to loss of these discharges predicts better treatment response 5
Plasma drug levels should guide subsequent dosing adjustments for ethosuximide (target 40-100 mcg/mL) 1
Management of Refractory Cases
Refractory CAE occurs in fewer than half of patients (approximately 22% in long-term follow-up studies) 3, 6
When first-line ethosuximide fails, switch to valproic acid or consider valproic acid-lamotrigine combination rather than adding medications 3, 5
Referral to pediatric neurology is warranted when the first medication fails 7
Critical Comorbidity Management
Approximately one-third of CAE patients develop attention deficit and cognitive disorders, requiring early neuropsychological screening 4
25% of patients require psychological and academic support despite good seizure control 6
Cognitive side effects should be specifically assessed during follow-up visits, as they significantly impact long-term psychosocial outcomes 4
Important Clinical Pitfalls
Do NOT use prophylactic anticonvulsants for febrile seizures, as this question concerns absence epilepsy, not febrile seizures—these are distinct entities 8
Do NOT prescribe ethosuximide for mixed seizure types; when generalized tonic-clonic seizures coexist with absence seizures, valproic acid or combination therapy is required 1
Do NOT overlook cognitive assessment—CAE should never be considered "benign" despite excellent seizure prognosis, as neuropsychological complications are common 4
Do NOT continue ineffective medication for prolonged periods; if seizures persist after reaching therapeutic doses, switch agents rather than continuing suboptimal therapy 3
Prognostic Factors
78.8% of patients achieve complete seizure remission with appropriate treatment 6
Only 4% experience seizure recurrence after treatment discontinuation when strict diagnostic criteria are applied 6
Presence of occipital intermittent rhythmic delta activity on EEG predicts favorable treatment response 5