Seizure-Free Period and Recurrence After Antiseizure Medication Withdrawal

What was studied

This systematic review examined whether the length of seizure freedom before antiseizure medication withdrawal was associated with seizure recurrence. Researchers searched three databases for literature published from inception through November 2, 2025.

They identified 45 studies involving 10,896 people with epilepsy. Of these, 22 studies with 3,933 participants were included in a random-effects meta-analysis. Subgroup analyses considered pediatric, adult, European, and Middle Eastern populations.

What they found

Across all patients, less than 5 years of seizure freedom before medication withdrawal was associated with higher recurrence risk: relative risk 1.49 (95% confidence interval 1.17–1.88; p=0.001).

The abstract lists higher relapse-risk estimates for pediatric patients with less than 3 years of seizure freedom, adults with less than 5 years, Europeans with less than 2 years, and Middle Eastern patients with less than 3 years. It reports five estimates for these four named subgroups: RR 1.70 (95% CI 1.20–2.39; p=0.003), RR 1.52 (95% CI 1.02–2.26; p=0.04), RR 2.11 (95% CI 1.48–2.99; p<0.001), RR 1.87 (95% CI 1.41–2.48; p<0.001), and RR 1.37 (95% CI 1.03–1.83; p=0.03). Because of this mismatch, not every estimate can be assigned confidently to a named subgroup.

For patients with at least 10 years of seizure freedom, the reported RR was 0.21 (95% CI 0.09–0.49; p<0.001). The abstract describes this as a higher risk, although an RR below 1 would ordinarily indicate lower relative risk depending on the reference group. The direction of this result therefore cannot be interpreted confidently from the abstract alone.

Limits of the evidence

The abstract does not provide absolute recurrence rates, follow-up duration, the definition of recurrence, or the comparison groups for every analysis. It also does not describe the included study designs or details such as epilepsy type, EEG findings, cause of epilepsy, medication regimen, or withdrawal speed.

The finding for at least 10 years of seizure freedom was based on limited participants and studies, and the authors state that it needs further validation. Reporting inconsistencies—including the stated direction of the RR of 0.21 and five estimates for four named subgroups—limit conclusions about an exact best time for withdrawal. The reported associations do not establish that waiting a specific number of years causes a change in recurrence risk.

For families and caregivers

The length of seizure freedom before stopping antiseizure medication may be one factor associated with relapse risk. Shorter seizure-free periods were associated with higher recurrence risk in several analyses, but this review does not establish one safe withdrawal time for everyone. Medication withdrawal should be considered with the treating clinician in light of the individual patient’s circumstances.

What to watch next

Further research should validate the finding for at least 10 years of seizure freedom and clearly report comparison groups, absolute recurrence rates, follow-up periods, and which estimates correspond to each subgroup. Clearer evidence is needed before defining an optimal withdrawal time for different epilepsy populations.

Terms in this summary

Antiseizure medication (ASM)

Medicine used to prevent or reduce seizures.

Systematic review

A structured search and assessment of available studies addressing a specific question.

Meta-analysis

A statistical method that combines results from multiple studies.

Relative risk (RR)

A comparison of risk between two groups; above 1 usually means higher risk and below 1 usually means lower risk, depending on the reference group.

95% confidence interval (CI)

A range showing the uncertainty around an estimated result; narrower ranges indicate greater precision.

Random-effects model

A method for combining studies that allows the true effect to differ across studies.

Recurrence

The return of seizures after a period without seizures.