What is the difference between Depakote (valproate) and Keppra (levetiracetam)?

Differences Between Depakote (Valproate) and Keppra (Levetiracetam)

Levetiracetam (Keppra) has fewer adverse effects and a more favorable side effect profile compared to valproate (Depakote), making it a preferred choice for many patients with seizure disorders, particularly those with brain tumors or on chemotherapy. 1

Mechanism of Action

• Valproate (Depakote):

  • Acts primarily as a voltage-gated sodium channel (VGSC) modulator
  • Inhibits GABA transaminase, increasing GABA levels in the brain (inhibitory enhancement) 1
  • Multiple mechanisms contribute to its anticonvulsant effect

• Levetiracetam (Keppra):

  • Acts as a synaptic vesicle protein 2A (SV2A) modulator 1
  • Has a novel and distinct mechanism of action compared to traditional antiepileptic drugs 2
  • Presumed to have inhibitory effects on excitatory neurotransmission

Side Effect Profile

• Valproate (Depakote):

  • Higher incidence of adverse effects 1, 3
  • Associated with higher hematologic toxicities, especially in patients on chemotherapy 1
  • Can cause thrombocytopenia and hepatotoxicity 1
  • May increase oxidative stress markers in the brain 4

• Levetiracetam (Keppra):

  • Generally well-tolerated with minimal adverse effects 1, 5
  • Fewer side effects compared to older antiepileptic drugs 1
  • May affect learning and memory in some studies 4
  • Can increase oxidative stress markers, though possibly less than valproate 4

Efficacy

• Valproate (Depakote):

  • Effective for various seizure types including generalized and focal seizures
  • Success rate of approximately 68-76% in controlling generalized convulsive status epilepticus 6
  • Drug of choice in many references for juvenile myoclonic epilepsy 3

• Levetiracetam (Keppra):

  • Similar efficacy to valproate in controlling seizures (74-86% success rate) 6, 3
  • Well-studied in brain tumor patients with good seizure control 1
  • Particularly effective when combined with other antiepileptic drugs 2

Drug Interactions

• Valproate (Depakote):

  • More likely to have drug interactions due to effects on hepatic enzymes
  • Can increase toxicity of concurrent medications

• Levetiracetam (Keppra):

  • Minimal pharmacokinetic interactions with other drugs 2
  • Safer option for patients on multiple medications

Special Considerations

• Driving Performance:

  • Levetiracetam has less impact on driving ability compared to older antiepileptic drugs 1
  • Valproate may have more significant effects on sensory-perceptual functions that could impact driving 1

• Use in Specific Populations:

  • Levetiracetam is often preferred for women of childbearing age due to lower teratogenic risk 3
  • Levetiracetam is recommended over older antiepileptic drugs for patients with brain tumors 1

Clinical Decision Making

When choosing between these medications, consider:

1. Patient characteristics: Age, gender, childbearing potential
2. Comorbidities: Presence of brain tumors, liver disease, or use of chemotherapy
3. Potential for drug interactions: Concurrent medications
4. Seizure type: Both are broad-spectrum but may have different efficacy for specific seizure types

Caution and Monitoring

• Both medications require regular monitoring, but valproate typically requires more intensive monitoring of liver function and blood counts
• Levetiracetam may require monitoring for behavioral side effects
• Both drugs should be initiated at lower doses and titrated to effective levels based on clinical response