How long should levetiracetam be continued after achieving sustained seizure freedom, and what is the recommended tapering schedule?

Levetiracetam Treatment Duration and Discontinuation

Discontinue levetiracetam after 2 seizure-free years, with the decision made after considering clinical, social, and personal factors and involving the patient and family. 1

Duration of Treatment Before Considering Discontinuation

• The WHO recommends considering antiepileptic drug discontinuation after 2 seizure-free years in patients with epilepsy, regardless of the specific agent used. 1
• This 2-year seizure-free threshold applies to levetiracetam monotherapy in the same manner as other first-line antiepileptic drugs (carbamazepine, phenobarbital, phenytoin, and valproic acid). 1

Factors Influencing the Discontinuation Decision

• The decision to withdraw or continue antiepileptic drugs must incorporate relevant clinical, social, and personal factors rather than following a rigid protocol. 1
• Patients who achieved seizure freedom on levetiracetam as first monotherapy have better long-term outcomes (54.4% seizure freedom) compared to those who switched from another agent (39.2%), suggesting these patients may be better candidates for eventual discontinuation. 2
• Patients with fewer than 5 seizures prior to starting levetiracetam were significantly more likely to achieve sustained seizure freedom (70 of 118 patients) compared to those with ≥5 seizures (42 of 110 patients; p=0.001), indicating pre-treatment seizure burden should inform discontinuation timing. 2
• In newly diagnosed epilepsy, 73% of patients achieved 6-month seizure freedom on levetiracetam, with 86% of those maintaining 1-year remission doing so at the lowest dose level (500 mg twice daily), suggesting patients controlled on low doses may be better candidates for discontinuation. 3

Tapering Schedule

• No specific tapering schedule for levetiracetam is provided in current guidelines, though the WHO framework emphasizes that discontinuation should be gradual and individualized. 1
• The absence of enzyme-inducing properties and minimal drug interactions with levetiracetam suggests tapering may be more straightforward than with traditional agents like phenytoin or carbamazepine, though no specific protocol is established. 2

Monitoring During and After Discontinuation

• Continuous EEG monitoring should be maintained for at least 24-48 hours after complete discontinuation when tapering in the hospital setting, as breakthrough seizures occur in more than 50% of refractory cases and are often only detectable by EEG without clinical manifestations. 4
• Outpatient EEG should be arranged after discontinuation, as an abnormal EEG predicts higher risk of seizure recurrence. 4

Special Populations and Considerations

• In post-stroke seizures, 77.1% of elderly patients (mean age 71.9 years) achieved 1-year seizure freedom on levetiracetam, with most controlled on 1000 mg daily, suggesting this population may also follow the 2-year discontinuation guideline. 5
• Women with epilepsy should have particular consideration for discontinuation attempts, as levetiracetam is preferred over valproate in women of childbearing potential due to lower teratogenic risk. 1

Common Pitfalls to Avoid

• Do not discontinue antiepileptic drugs routinely after a first unprovoked seizure—treatment should be established first before considering the 2-year seizure-free period. 1
• Neuropsychiatric symptoms (aggression, mood swings, irritability, depression) occurred in 7.9% of patients on levetiracetam monotherapy and were the most common reason for discontinuation, so these symptoms should not be mistaken for seizure recurrence during tapering. 2
• Ensure medication compliance is verified before attributing breakthrough seizures to inadequate treatment, as non-compliance is a common cause of seizure recurrence. 4