The effect of seizure-free period on seizure recurrence following antiseizure medication withdrawal: a systematic review and meta-analysis
In brief
Fewer than five seizure-free years is linked to 49% higher relapse risk
In a meta-analysis of 22 studies involving 3,933 people with epilepsy, those seizure-free for less than five years before stopping medication had a 49% higher risk of seizure recurrence than those seizure-free longer. The findings varied by age and region, and the apparent lower risk after 10 or more seizure-free years needs validation; the best withdrawal timing remains uncertain.
- Journal
- Journal of neurology (Q1)
- Published
- 20 October 2026
- Study design
- Systematic review of cohort studies
- Evidence level
- Level 2, Moderate (CEBM 2a)
- Authors
- Hongye Zhou, Weihua Zhou, Xin Xu
- PMID
- 42900237
- DOI
- 10.1007/s00415-026-14217-x
Why clinicians should know about it
- Picked for Neurology (clinical) (paper of the day, 23 October 2026): Meta-analysis informs seizure recurrence after antiseizure medication withdrawal
Abstract
BACKGROUND: The seizure-free period before withdrawal is an important factor that influences the risk of epilepsy relapse. Our study aimed to evaluate the effect of the seizure-free period on the relapse risk after antiseizure medication(ASM) withdrawal in epilepsy populations and identify the optimal timing of ASM withdrawal. METHODS: The Cochrane Central Register of Controlled Trials, PubMed and Web of Science were searched for literature published from inception to November 2, 2025. The primary outcome was the relapse risk of epilepsy patients after ASM withdrawal. Random-effects meta-analysis models were used to estimate the pooled recurrence risk based on heterogeneity. RESULTS: We identified 45 studies with 10,896 patients; 22 studies with 3933 patients were included in the meta-analysis. According to the analyses of all the epilepsy patients, there was a greater risk of recurrence in patients with <5 years of seizure freedom (RR (95% CI) 1.49 (1.17-1.88), p=0.001). Our results also revealed that patients with ≥10 years of seizure freedom had a higher risk of recurrence (RR (95% CI) 0.21 (0.09-0.49), p<0.001); however, it needs further validation due to the limited number of participants and the inclusion of studies. With respect to the subgroup analyses, paediatric patients who had <3 years of seizure freedom, adult patients who had <5 years of seizure freedom, European patients who had <2 years of seizure freedom and Middle Eastern patients who had <3 years of seizure freedom had a higher relapse risk(RR(95% CI) 1.70(1.20-2.39),p=0.003; RR(95% CI) 1.52(1.02-2.26),p=0.04; RR(95% CI) 2.11(1.48-2.99),p<0.001; RR(95% CI) 1.87 (1.41-2.48),p<0.001; RR(95% CI) 1.37(1.03-1.83),p=0.03). SIGNIFICANCE: The seizure-free period may be an important factor that influences patients' risk of recurrence after ASM withdrawal. Without strong recommendations and evidence regarding the seizure-free period and risk of seizure recurrence, this meta-analysis provides evidence of the optimal timing of ASM withdrawal in epilepsy subpopulations.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.