How to switch a patient with absence seizures from Lamictal (lamotrigine) 125mg twice a day (BID) to ethosuximide with a taper?

Switching from Lamotrigine to Ethosuximide for Adult Absence Seizures

For an adult with absence seizures currently on lamotrigine 125mg BID, initiate ethosuximide while gradually tapering lamotrigine over 2-4 weeks using a cross-titration approach, as abrupt withdrawal of anticonvulsants may precipitate absence status epilepticus. 1

Understanding the Medication Switch

Ethosuximide is the optimal first-line treatment for pure absence seizures, demonstrating superior efficacy (45% seizure freedom) compared to lamotrigine (21% seizure freedom) in the largest comparative trial. 2 While lamotrigine can be effective for absence seizures, ethosuximide remains the drug of choice when absence seizures occur without generalized tonic-clonic seizures. 3, 2

Cross-Titration Protocol

Week 1-2: Initiation Phase

• Continue lamotrigine 125mg BID (current dose) 1
• Start ethosuximide at 250mg once daily, preferably at bedtime or with the main meal to minimize gastrointestinal side effects 1
• Monitor for initial tolerability

Week 2-3: Titration Phase

• Increase ethosuximide to 250mg twice daily (500mg total daily dose) 1, 4
• Reduce lamotrigine to 125mg once daily 5
• The gradual reduction is critical as abrupt withdrawal may precipitate absence status epilepticus 1

Week 3-4: Transition Phase

• Increase ethosuximide to target therapeutic dose of 750mg-1000mg daily in divided doses (typically 500mg in morning, 250-500mg in evening) 4
• Discontinue lamotrigine completely 5
• Therapeutic plasma ethosuximide concentration should be 40-100 mcg/mL 4

Critical Monitoring Parameters

During the Taper Period

• Monitor for breakthrough absence seizures daily, as lamotrigine when used alone in mixed epilepsy types may have been providing some seizure control 1
• Watch for signs of absence status epilepticus: prolonged confusion, continuous spike-wave discharges on EEG 1
• Assess for withdrawal symptoms from lamotrigine, though these are typically mild given its relatively long half-life 5

After Ethosuximide Initiation

• Monitor for infection symptoms (sore throat, fever) as ethosuximide can rarely cause blood dyscrasias 1
• Assess for common side effects: gastrointestinal upset, drowsiness, headache 4
• Check plasma ethosuximide levels 2-4 weeks after reaching maintenance dose to ensure therapeutic range of 40-100 mcg/mL 4

Important Caveats

If this patient has BOTH absence seizures AND generalized tonic-clonic seizures, do NOT switch to ethosuximide alone, as it is ineffective for tonic-clonic seizures and may increase their frequency. 1, 3, 2 In such cases, valproate would be the preferred agent. 3, 2

Ethosuximide may impair mental and physical abilities required for driving or operating machinery, so counsel the patient accordingly during the transition period. 1

If a rash develops during the taper, this requires immediate physician evaluation as it may herald a serious medical event, though this is more commonly associated with lamotrigine than ethosuximide. 1

Expected Outcomes

• 95% of patients achieve 50-100% seizure control with ethosuximide 4
• Complete seizure freedom occurs in approximately 19-45% of patients depending on the study population 2, 4
• Ethosuximide does not impair psychometric performance and may actually improve cognitive function in many patients 4
• Side effects are typically minor and rarely require drug withdrawal 4