From the Research
Ethosuximide is the best drug for treating absence seizures, as it has been shown to be effective in controlling seizures with minimal side effects, as demonstrated in a large randomised, parallel double-blind controlled trial comparing ethosuximide, lamotrigine, and sodium valproate in 453 children with newly diagnosed childhood absence epilepsy 1.
Mechanism of Action
Ethosuximide works by blocking T-type calcium channels in the thalamus, which are responsible for the abnormal brain activity that causes absence seizures. These channels generate rhythmic firing patterns in thalamic neurons that contribute to the characteristic 3-Hz spike-and-wave discharges seen on EEG during absence seizures. By inhibiting these channels, ethosuximide disrupts the synchronized neuronal activity that leads to seizures.
Dosage and Administration
The typical starting dose for ethosuximide is 250 mg daily for children and 500 mg daily for adults, usually divided into two doses. The dose can be gradually increased as needed to control seizures, with most patients requiring 20-40 mg/kg/day. Blood levels of 40-100 μg/mL are generally considered therapeutic.
Side Effects and Treatment Duration
Common side effects of ethosuximide include gastrointestinal symptoms, headache, and dizziness, which are usually mild and transient. If ethosuximide alone is insufficient, valproic acid or lamotrigine may be added or substituted. Treatment typically continues for at least two seizure-free years before considering gradual withdrawal under medical supervision.
Comparison with Other Treatments
A large randomised, parallel double-blind controlled trial comparing ethosuximide, lamotrigine, and sodium valproate in 453 children with newly diagnosed childhood absence epilepsy found that at 12 months, the freedom-from-failure rates for ethosuximide and valproic acid were similar and were higher than the rate for lamotrigine 1. The frequency of treatment failures due to lack of seizure control and intolerable adverse events was significantly different among the treatment groups, with the largest proportion of lack of seizure control in the lamotrigine cohort, and the largest proportion of adverse events in the valproic acid group. Overall, this large study demonstrates the superior effectiveness of ethosuximide and valproic acid compared to lamotrigine as initial monotherapy aimed to control seizures without intolerable adverse effects in children with childhood absence epilepsy.