From the FDA Drug Label
CLINICAL PHARMACOLOGY Ethosuximide suppresses the paroxysmal three cycle per second spike and wave activity associated with lapses of consciousness which is common in absence (petit mal) seizures. The frequency of epileptiform attacks is reduced, apparently by depression of the motor cortex and elevation of the threshold of the central nervous system to convulsive stimuli.
An appropriate first-line drug of choice for this seizure disorder is Ethosuximide. Another option is Lamotrigine, however the provided drug label only mentions Ethosuximide.
- Key points:
- Ethosuximide is effective in treating absence seizures.
- The patient's history of mild depression treated with fluoxetine does not directly influence the choice of Ethosuximide as a first-line treatment for absence seizures. 1
From the Research
Ethosuximide is the recommended first-line treatment for this 12-year-old boy with absence seizures who is taking fluoxetine for mild depression. The typical starting dose is 250 mg once or twice daily, gradually increasing to a maintenance dose of 20-40 mg/kg/day divided into two doses as needed for seizure control. Maximum daily dose should not exceed 1500 mg. Treatment effectiveness should be monitored through clinical response and EEG findings, with the goal of complete seizure freedom. Ethosuximide is preferred over valproate or lamotrigine in this case because it has the best efficacy for absence seizures with fewer cognitive side effects and no significant drug interactions with fluoxetine, as supported by a large randomised, parallel double-blind controlled trial comparing ethosuximide, lamotrigine and sodium valproate in children with newly diagnosed childhood absence epilepsy 2, 3. Common side effects include gastrointestinal disturbances, headache, and fatigue, which typically improve with time. Parents should be advised that improvement may take several weeks, and the medication should not be stopped abruptly. Regular follow-up appointments every 3-6 months are recommended to assess seizure control, side effects, and potentially adjust dosing as the child grows.
Some key points to consider when treating absence seizures include:
- The importance of monitoring treatment effectiveness through clinical response and EEG findings
- The potential for cognitive side effects with certain medications, such as valproate
- The need for regular follow-up appointments to assess seizure control and adjust dosing as needed
- The potential for drug interactions with other medications, such as fluoxetine, and the need to choose a medication with minimal interactions.
It's also worth noting that other medications, such as lamotrigine, may be effective in treating absence seizures, but the evidence suggests that ethosuximide is the optimal initial empirical monotherapy for children and adolescents with absence seizures 2, 3.
In terms of specific treatment options, the study by 3 found that ethosuximide and valproic acid had similar freedom-from-failure rates at 12 months, and were higher than the rate for lamotrigine. The frequency of treatment failures due to lack of seizure control and intolerable adverse events was also 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, the evidence suggests that ethosuximide is the preferred first-line treatment for absence seizures in children and adolescents, due to its efficacy, safety profile, and minimal drug interactions.