What alternative or add-on treatments can be given to a patient with uncontrolled absence seizures already on Keppra (levetiracetam)?

Management of Absence Seizures in Patients Already on Levetiracetam

For patients with uncontrolled absence seizures already on levetiracetam (Keppra), valproate should be added as the preferred second-line treatment due to its superior efficacy for generalized seizures. 1

Rationale for Valproate as Add-on Therapy

Levetiracetam alone has limited effectiveness for absence seizures, with studies showing:

• Only about 25% of children with absence epilepsy achieve seizure freedom with levetiracetam 2
• When levetiracetam fails, it's typically due to incomplete seizure control (59% of cases) 2

Valproate offers several advantages as an add-on therapy:

• High success rate (88%) in controlling seizures 1
• Specifically recommended for generalized seizures with superior efficacy 1
• Shown to be effective in refractory status epilepticus with 68-88% efficacy 3

Dosing and Administration

• Initial valproate dosing: 20-30 mg/kg IV loading dose for urgent control 1
• Maintenance oral dosing should be established based on clinical response
• When effective, lower doses of levetiracetam (around 29 mg/kg/day) may be sufficient in combination therapy 2

Important Considerations and Contraindications

• Women of childbearing potential: Avoid valproate due to significant teratogenicity risks; consider lamotrigine instead 1
• Liver disease: Avoid valproate due to hepatotoxicity risk; consider lamotrigine or lacosamide 1
• Monitoring: Regular follow-up to assess efficacy and adverse effects is essential 1

Alternative Options if Valproate is Contraindicated

1. Ethosuximide: Particularly effective for pure absence seizures 4
2. Lamotrigine: Good option for women of childbearing potential with favorable side effect profile 1
3. Lacosamide: Can be rapidly titrated in urgent situations with minimal drug interactions 1

Common Adverse Effects to Monitor

• Valproate: GI disturbances, tremor 1
• Levetiracetam: Behavioral issues, irritability
• Combination therapy: Increased risk of adverse effects and drug interactions 5

Follow-up Recommendations

• EEG monitoring every 3-6 months to assess treatment efficacy 1
• Regular assessment of seizure frequency and characteristics 1
• Laboratory monitoring including baseline renal and hepatic function 1

If absence seizures remain uncontrolled despite optimized combination therapy with levetiracetam and valproate (or an alternative second agent), referral to a specialized epilepsy center for comprehensive evaluation and consideration of additional treatment options is warranted.