Does Keppra (levetiracetam) need to be tapered off?

Tapering Keppra (Levetiracetam)

Yes, Keppra (levetiracetam) should be gradually tapered off rather than abruptly discontinued to minimize the risk of withdrawal seizures. 1

Why Tapering is Necessary

Levetiracetam, like other antiepileptic drugs, requires gradual withdrawal to minimize the potential for increased seizure frequency. The FDA drug label explicitly states that "antiepileptic drugs, including levetiracetam, should be withdrawn gradually to minimize the potential of increased seizure frequency." 1

This recommendation is supported by clinical guidelines that emphasize the importance of tapering antiepileptic medications to prevent breakthrough seizures and withdrawal symptoms.

Recommended Tapering Schedule

While there is no universally standardized tapering protocol specifically for levetiracetam in the provided evidence, a gradual approach similar to other antiepileptic drugs is recommended:

• The Italian League Against Epilepsy recommends a minimum tapering period of 6 months for antiepileptic drugs 2
• For most patients, a reasonable approach would be to reduce the dose by approximately 25% every 2-4 weeks
• The tapering schedule should be slower for patients with:
  • History of difficult-to-control seizures
  • Multiple risk factors for seizure recurrence
  • Longer duration of epilepsy

Risk Factors for Recurrence During Tapering

Several factors may increase the risk of seizure recurrence during levetiracetam tapering:

• Abnormal EEG at the time of discontinuation
• Documented etiology of seizures (including mental retardation, perinatal insults)
• Partial seizures
• Older age at disease onset 2
• Multiple risk factors in combination increase recurrence risk significantly

Monitoring During Tapering

During the tapering process, patients should be:

• Monitored for at least 2 years after complete discontinuation 2
• Observed for signs of breakthrough seizures
• Assessed for behavioral changes (as levetiracetam is associated with behavioral abnormalities) 1

Special Considerations

• Behavioral symptoms: Levetiracetam is associated with behavioral abnormalities including aggression, irritability, and mood disorders. These should be monitored during the tapering process 1, 3
• Risk factors for behavioral issues: Patients with a history of psychiatric disorders and those with symptomatic generalized epilepsy may be at higher risk for behavioral abnormalities during levetiracetam use and potentially during tapering 3
• Tapering rate: Slower titration of levetiracetam is associated with fewer behavioral side effects 3

Clinical Pitfalls to Avoid

1. Abrupt discontinuation: Never stop levetiracetam suddenly as this significantly increases seizure risk
2. Ignoring breakthrough seizures: If seizures occur during tapering, the previous effective dose should be reinstated
3. Overlooking behavioral changes: Monitor for worsening of behavioral symptoms during the tapering process
4. Insufficient monitoring: Patients should be followed for at least 2 years after complete discontinuation

The decision to discontinue levetiracetam should always be discussed with the patient, considering both the risks of seizure recurrence and the potential complications of long-term treatment.