Longer Seizure-Free Periods Linked to Lower Relapse Risk After Epilepsy Drug Withdrawal

People with epilepsy who have been seizure-free for at least five years before stopping their antiseizure medication appear to face a lower risk of seizure recurrence than those who withdraw sooner, according to a systematic review and meta-analysis published in the Journal of Neurology. The analysis, which pooled data from 22 studies involving 3,933 patients, found that a shorter seizure-free period before withdrawal was consistently associated with a higher chance of seizures returning.

The research team, led by Hongye Zhou, Weihua Zhou and Xin Xu, set out to evaluate how the length of the seizure-free period before withdrawal influences relapse risk, and to identify optimal timing for stopping antiseizure medication in different epilepsy populations. The seizure-free period before withdrawal is described in the study as an important factor influencing the risk of epilepsy relapse.

To assemble the evidence, the researchers searched the Cochrane Central Register of Controlled Trials, PubMed and Web of Science for literature published from inception to November 2, 2025. In total, they identified 45 studies covering 10,896 patients, of which 22 studies with 3,933 patients could be included in the meta-analysis. The primary outcome was the risk of relapse among epilepsy patients after antiseizure medication withdrawal, and random-effects meta-analysis models were used to estimate pooled recurrence risk in light of heterogeneity between studies.

Across all epilepsy patients, the analysis showed a greater risk of recurrence in those with less than five years of seizure freedom before withdrawal, with a relative risk of 1.49 (95% confidence interval 1.17–1.88, p=0.001). This means that, in the pooled studies, patients withdrawing after a shorter seizure-free period had roughly a 49% higher relative risk of seizures returning compared with the reference group.

The study also examined patients with ten or more years of seizure freedom. These patients showed a markedly lower relative risk of recurrence, reported as 0.21 (95% confidence interval 0.09–0.49, p<0.001). However, the authors cautioned that this finding needs further validation because of the limited number of participants and studies contributing to that estimate. Until more data accumulate, the very long seizure-free period result should be interpreted with care.

Subgroup analyses pointed to differences across age groups and regions. Paediatric patients who had less than three years of seizure freedom before withdrawal had a higher relapse risk, with a relative risk of 1.70 (95% confidence interval 1.20–2.39, p=0.003). Adult patients with less than five years of seizure freedom also faced elevated risk, at a relative risk of 1.52 (95% confidence interval 1.02–2.26, p=0.04).

Geographic patterns emerged as well. European patients who had less than two years of seizure freedom showed a higher relapse risk, with a relative risk of 2.11 (95% confidence interval 1.48–2.99, p<0.001). Middle Eastern patients with less than three years of seizure freedom likewise had increased risk, reported at a relative risk of 1.87 (95% confidence interval 1.41–2.48, p<0.001), and an additional subgroup estimate of 1.37 (95% confidence interval 1.03–1.83, p=0.03) was also reported in the results.

The authors conclude that the seizure-free period may be an important factor influencing patients’ risk of recurrence after antiseizure medication withdrawal. They note that current evidence on the seizure-free period and seizure recurrence risk lacks strong recommendations, and position their meta-analysis as providing evidence on the optimal timing of withdrawal in epilepsy subpopulations rather than definitive guidance.

As with any meta-analysis, the findings reflect pooled observational data from heterogeneous studies rather than a randomized trial of withdrawal timing, and the authors themselves flag the need for further validation of some estimates. Nevertheless, the review offers a quantitative synthesis of one of the most consequential decisions in epilepsy care: when it may be reasonably safe to stop medication. The full analysis appears in Volume 273, article number 671 of the Journal of Neurology.

Subject of Research: The effect of the seizure-free period before antiseizure medication withdrawal on seizure recurrence risk in epilepsy

Article Title: The effect of seizure-free period on seizure recurrence following antiseizure medication withdrawal: a systematic review and meta-analysis

Article References: Zhou, H., Zhou, W., & Xu, X. (2026). The effect of seizure-free period on seizure recurrence following antiseizure medication withdrawal: a systematic review and meta-analysis. Journal of Neurology, 273(11), Article 671. https://doi.org/10.1007/s00415-026-14217-x

Image Credits: AI Generated

DOI: 10.1007/s00415-026-14217-x

Keywords: epilepsy, antiseizure medication, seizure recurrence, drug withdrawal, meta-analysis, seizure-free period, relapse risk, systematic review, paediatric epilepsy, Journal of Neurology, effect, seizure-free