When can a patient with a history of seizures, currently stable on Keppra (levetiracetam), taper off this medication?

When to Taper Off Keppra (Levetiracetam)

Discontinuation of levetiracetam should be considered after 2 seizure-free years, with tapering performed by decreasing the dose by 500 mg increments every 1-2 weeks. 1, 2

Eligibility Criteria for Tapering

Before initiating a taper, the following conditions must be met:

• Seizure-free duration: The patient must have been completely seizure-free for at least 24 consecutive months 1
• Resolution of underlying pathology: Imaging studies should demonstrate resolution of any cystic lesions or structural abnormalities that initially caused seizures 1
• Absence of high-risk features: Patients should not have residual cystic lesions, calcifications on neuroimaging, or a history of breakthrough seizures or more than 2 seizures prior to treatment 1

The WHO guidelines for epilepsy management support this 2-year seizure-free threshold as the standard for considering antiepileptic drug withdrawal, emphasizing that the decision should involve consideration of relevant clinical, social, and personal factors with patient and family involvement 1.

Recommended Tapering Protocol

The evidence-based tapering schedule involves reducing levetiracetam by 500 mg increments every 1-2 weeks 2. This approach is based on the standard titration guidance used when initiating levetiracetam and has been established as well-tolerated 2.

• Use the slower end of the range (2-week intervals) for patients with more severe epilepsy history or those who had recent seizures before achieving seizure freedom 2
• Use faster tapering (1-week intervals) for patients with well-controlled seizures for extended periods 2

Critical Monitoring During Taper

Close surveillance is essential throughout the tapering process:

• Assess seizure frequency at each follow-up visit to detect any increase in seizure activity 2
• Monitor for breakthrough seizures at each dose reduction, as patients are at risk for seizure recurrence when antiepileptic medications are withdrawn 2
• Obtain levetiracetam serum levels if breakthrough seizures occur to assess whether therapeutic levels are being maintained 2

When NOT to Taper

Certain clinical scenarios contraindicate tapering:

• Patients requiring anticoagulant therapy should not undergo tapering unless platelet counts reach at least 100 × 10⁹/L (this applies to specific contexts like immune thrombocytopenia, but the principle of avoiding tapering in high-risk bleeding scenarios is relevant) 1
• Patients with unstable seizure control or those requiring maximal doses for prolonged periods should not be considered candidates for tapering 1
• Women of childbearing potential on combination therapy with valproate require special consideration, as valproate carries significant teratogenic risks 1

Management of Breakthrough Seizures During Taper

If seizures recur during the tapering process:

• Hold at the current dose for an additional 2-4 weeks before attempting further reduction 2
• Consider maintaining the patient on a lower maintenance dose rather than complete discontinuation 2
• Re-introduce the medication at the minimum dose needed to trigger a response if seizures occur below 30 × 10⁹/L platelet count or if quality of life is reduced 1

Special Populations

Neurocysticercosis

For patients with seizures secondary to neurocysticercosis, tapering can be considered after 6 months of being seizure-free following resolution of the lesion, provided there are no risk factors for recurrent seizures such as residual calcifications 1.

Brain Metastases

For patients who were started on anticonvulsants in preparation for surgery for brain metastases and who have no history of seizures, discontinuation can be strongly considered after the perioperative period 1. Prophylactic anticonvulsants should be withheld for patients with no history of seizures who are not undergoing surgery 1.

Common Pitfalls to Avoid

• Abrupt discontinuation significantly increases seizure risk in patients with established epilepsy 2
• Do not taper if the patient has had breakthrough seizures or more than 2 seizures prior to achieving seizure control 1
• Avoid tapering in patients with persistent structural abnormalities on neuroimaging 1