Treatment of Petit Mal (Absence) Seizures
Ethosuximide or valproate are the first-line treatments for typical absence seizures, with ethosuximide controlling 70% of absences and valproate controlling 75%, though valproate is preferred when other generalized seizure types coexist. 1, 2, 3
First-Line Monotherapy Options
Ethosuximide (Preferred for Pure Absence Seizures)
- Start with 250 mg/day for children 3-6 years, or 500 mg/day for patients ≥6 years old 1
- Increase by 250 mg every 4-7 days until seizures are controlled with minimal side effects 1
- Optimal dose is 20 mg/kg/day, targeting plasma levels of 40-100 mcg/mL 1
- Achieves 70% seizure control in absence epilepsy 2
- Critical limitation: Does NOT control generalized tonic-clonic seizures or myoclonic jerks—unsuitable as monotherapy if these coexist 2, 4
Valproate (Preferred When Multiple Seizure Types Present)
- Controls 75% of absence seizures, PLUS 70% of generalized tonic-clonic seizures and 75% of myoclonic jerks 2
- Dose: 20-30 mg/kg/day, divided doses 5
- Valproate and ethosuximide show equal efficacy for pure absence seizures (52% vs 47% probability of seizure freedom) 3
- Major advantage: Broad spectrum—treats all generalized seizure types simultaneously 6, 4
Lamotrigine (Alternative First-Line)
- May control 50-60% of absences and generalized tonic-clonic seizures 2
- Warning: Can worsen myoclonic jerks—avoid in juvenile myoclonic epilepsy 2
- Skin rashes are common (11% incidence) 7
- Shows 61% probability of achieving seizure freedom for generalized tonic-clonic seizures 3
Critical Safety Considerations
Valproate Contraindications and Warnings
- ABSOLUTE CONTRAINDICATION: Women of childbearing potential without effective contraception 6, 2
- Teratogenic risk: Significantly increased fetal malformations and neurodevelopmental delay 6
- Fatal hepatotoxicity risk: 1 in 20,000 overall, but 1 in 600-800 in children <2 years on polytherapy 6
- Long-term side effects: Weight gain >5.5 kg (20% of patients), hair loss (12%), tremor (45%) 6, 7
Drug Interactions
- Carbapenems (meropenem, imipenem, ertapenem) dramatically reduce valproate levels and precipitate breakthrough seizures—AVOID concurrent use 5
Treatment Algorithm
Step 1: Determine seizure syndrome
- Pure absence seizures only → Ethosuximide is equally effective and avoids valproate's side effects 2, 3
- Absence + generalized tonic-clonic or myoclonic seizures → Valproate is mandatory first choice 2, 4
- Women of childbearing age → Lamotrigine preferred; valproate contraindicated 6, 2
Step 2: Initiate monotherapy and titrate
- Ethosuximide: Start 250-500 mg/day, increase by 250 mg every 4-7 days to target 20 mg/kg/day 1
- Valproate: Start 10-15 mg/kg/day, increase to 20-30 mg/kg/day 5
- Monitor for 90% seizure precipitation with hyperventilation in untreated patients 2
Step 3: If monotherapy fails after achieving therapeutic levels
- Add low-dose lamotrigine to valproate—may have dramatic beneficial effect 2
- Alternative: Combine ethosuximide with valproate for resistant absences 2
- Clonazepam useful for absences with myoclonic components 8, 2
Common Pitfalls to Avoid
- Never use carbamazepine or phenytoin for absence seizures—they are ineffective and may worsen absences 4
- Do not use ethosuximide alone if any history of generalized tonic-clonic seizures—it provides no protection 2, 4
- Verify medication adherence before assuming treatment failure—non-compliance is the most common cause of breakthrough seizures 5
- Do not add multiple drugs before optimizing monotherapy to therapeutic levels 5
Special Clinical Scenarios
Absence Status Epilepticus
- Occurs in 30% of patients with typical absence epilepsy 2
- More common in syndromes like idiopathic generalized epilepsy with perioral myoclonia 2
- Requires IV valproate 20-30 mg/kg over 5-20 minutes (88% efficacy, 0% hypotension risk) 9, 5
Childhood Absence Epilepsy
- Absences are severe and the only seizure type 2
- Ethosuximide or valproate equally effective—choose based on side effect profile and patient factors 2, 3