What are the treatment options for absence seizures?

Treatment of Absence Seizures

For childhood absence epilepsy, ethosuximide is the first-line treatment of choice, achieving 45-70% seizure freedom with the best tolerability profile, while valproic acid should be reserved for patients who also have generalized tonic-clonic seizures. 1, 2

First-Line Monotherapy Options

Ethosuximide (Preferred for Pure Absence Seizures)

• Start at 15 mg/kg/day and increase by 5-10 mg/kg weekly until seizures are controlled, up to a maximum of 60 mg/kg/day 3, 4
• Achieves seizure freedom in 45-70% of patients with childhood absence epilepsy 1, 2
• Therapeutic serum concentration ranges from 50-100 mcg/mL 3
• Critical limitation: Ethosuximide is ineffective against generalized tonic-clonic seizures, making it unsuitable as monotherapy if other seizure types coexist 1, 2

Valproic Acid (First Choice When GTCS Coexist)

• Controls absence seizures in 75% of patients and also controls generalized tonic-clonic seizures (70%) and myoclonic jerks (75%) 1
• Start at 15 mg/kg/day, increasing by 5-10 mg/kg weekly to achieve optimal response, typically below 60 mg/kg/day 3
• Therapeutic range: 50-100 mcg/mL 3
• Major concern: Higher rate of intolerable adverse events (33%) compared to ethosuximide (25%) and lamotrigine (20%) 2
• Contraindicated in women of childbearing potential due to teratogenicity and neurodevelopmental risks 1, 5

Lamotrigine (Third-Line Option)

• Achieves only 21% seizure freedom compared to 45% with ethosuximide and 44% with valproate 2
• Significantly less effective than ethosuximide or valproate for absence seizures 2
• May control 50-60% of absences but can worsen myoclonic jerks 1
• Skin rashes are common adverse effects 1

Treatment Algorithm

Step 1: Determine seizure types present

• If pure absence seizures only → Start ethosuximide 1, 2
• If absence seizures + generalized tonic-clonic seizures → Start valproic acid 1, 2
• If absence seizures + myoclonic jerks → Start valproic acid 1

Step 2: If first monotherapy fails after adequate trial

• Switch to the alternative first-line agent (ethosuximide ↔ valproic acid) 1, 6
• Lamotrigine may be considered as second-line monotherapy, though less effective 2

Step 3: For drug-resistant absence seizures

• Combine low-dose lamotrigine with valproic acid, which may have dramatic beneficial effects 1
• Alternative combinations: ethosuximide + valproic acid, or any two of the three first-line agents 1, 6
• Consider levetiracetam, topiramate, or zonisamide for refractory cases 6
• Clonazepam may be useful for absences with myoclonic components 1
• Acetazolamide may serve as adjunctive therapy 1

Critical Pitfalls to Avoid

Never use carbamazepine, oxcarbazepine, vigabatrin, or gabapentin - these agents may worsen absence seizures 5

Avoid phenytoin and phenobarbital as first-line agents - they are only partially effective and have unacceptable side effects, though they may have limited utility in resistant cases 1, 5

Do not abruptly discontinue antiepileptic drugs - this can precipitate status epilepticus with life-threatening consequences 3

Special Considerations for Women

In women of childbearing age, avoid valproic acid whenever possible due to teratogenicity risks 1, 5

• If valproic acid must be used, concurrent folic acid supplementation is mandatory 1
• Consider ethosuximide (if no GTCS) or lamotrigine as safer alternatives, though efficacy may be compromised 5

Monitoring Parameters

• Serum drug levels should be measured if satisfactory clinical response is not achieved at appropriate doses 3
• Monitor for thrombocytopenia with valproic acid, especially at trough concentrations >110 mcg/mL (females) or >135 mcg/mL (males) 3
• Assess seizure control with hyperventilation testing, which precipitates absences in 90% of untreated patients 1