What is the treatment for multiple focal seizures with Keppra (levetiracetam)?

Levetiracetam (Keppra) for Multiple Focal Seizures

Levetiracetam is highly effective as adjunctive therapy for drug-resistant focal seizures, with 38-52% of patients achieving ≥50% seizure reduction, and should be dosed at 1000-3000 mg/day in adults (or 60 mg/kg/day in children), initiated at 1000 mg/day and increased by 1000 mg every 2 weeks. 1, 2

FDA-Approved Dosing and Administration

Adults (≥16 years):

• Start at 1000 mg/day divided twice daily (500 mg BID) 1
• Increase by 1000 mg/day every 2 weeks as needed 1
• Maximum recommended dose: 3000 mg/day 1
• Doses above 3000 mg/day provide no additional benefit 1

Children (4 to <16 years):

• Start at 20 mg/kg/day in 2 divided doses (10 mg/kg BID) 1
• Increase every 2 weeks by 20 mg/kg increments 1
• Target dose: 60 mg/kg/day (30 mg/kg BID) 1
• If 60 mg/kg/day is not tolerated, reduce to lower dose 1

Clinical Efficacy Data

Response rates (≥50% seizure reduction):

• Adults: 39% respond to levetiracetam vs 16% to placebo 3
• Children: 52% respond to levetiracetam vs 25% to placebo 3
• Number Needed to Treat: 5 for adults, 4 for children 3

At the 2000 mg/day dose specifically:

• 37% of adults achieve ≥50% seizure reduction 3
• 4.91 times more effective than placebo 3

Dose-response relationship:

• Each 1000 mg increase in dose raises odds of response by 40% 4
• 500 mg/day is NOT more effective than placebo 5
• Doses above 3500 mg/day may paradoxically increase seizures and psychiatric side effects 6

Position in Treatment Algorithm

For established status epilepticus (second-line agent):

• Administer 30 mg/kg IV over 5 minutes after benzodiazepines fail 4
• Success rate: 68-73% for benzodiazepine-refractory seizures 4
• Minimal cardiovascular effects—no hypotension risk 4
• No cardiac monitoring required 4

For chronic focal epilepsy:

• Levetiracetam is indicated as adjunctive therapy, not first-line monotherapy 1
• Lamotrigine remains superior for first-line treatment of focal epilepsy 7
• Levetiracetam is appropriate when first-line agents fail or are contraindicated 7

Adverse Effects Profile

Common side effects:

• Somnolence: 13% of patients (RR 1.62 vs placebo) 3
• Infection: increased risk (RR 1.76) 3
• Behavioral changes: 1% in adults but 23% in children (RR 1.90) 3, 5

Critical dosing pitfall:

• Do NOT exceed 3500 mg/day—higher doses cause paradoxical seizure worsening and psychiatric effects 6

Behavioral monitoring in children:

• 23% of children experience behavioral changes 3
• Use Cornell Assessment of Pediatric Delirium (CAPD) tool for monitoring 5
• Consider prophylactic use (10 mg/kg every 12 hours for 30 days) in children with CNS disease or seizure history receiving CAR T-cell therapy 5

Comparative Effectiveness

Levetiracetam vs other second-line agents for status epilepticus:

• Levetiracetam 30 mg/kg: 68-73% efficacy, 0% hypotension 4
• Valproate 30 mg/kg: 88% efficacy, 0% hypotension 4
• Fosphenytoin 20 mg PE/kg: 84% efficacy, 12% hypotension 4
• Phenobarbital 20 mg/kg: 58% efficacy, high respiratory depression risk 4

For chronic focal epilepsy:

• Lamotrigine is superior to levetiracetam for time to 12-month remission (HR 1.32) 7
• Lamotrigine is superior for time to treatment failure (HR 0.60) 7
• Levetiracetam is more costly and less effective than lamotrigine as first-line therapy 7

Long-Term Considerations

• No evidence of tolerance development with prolonged treatment 6
• Effective against all focal seizure types regardless of focus localization 6
• 18.8% of patients become seizure-free with add-on levetiracetam 6
• Treatment withdrawal rate similar to placebo (RR 0.98) 3

Administration Considerations

• Can be given with or without food 1
• Oral solution required for children ≤20 kg 1
• Tablets or oral solution acceptable for children >20 kg 1
• Rapid titration does not decrease tolerability 6
• IV formulation allows rapid loading up to 60 mg/kg 5