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Evidence summaries

Immediate Antiepileptic Drug Treatment, Versus Placebo, Deferred, or No Treatment for First Unprovoked Seizure

Treatment of the first unprovoked seizure reduces the risk of a subsequent seizure but does not affect the proportion of patients in remission in the long-term. Antiepileptic drugs are associated with adverse events, and there is no evidence that they reduce mortality. Level of evidence: "A"

Summary

A Cochrane review [Abstract] 1 included 6 studies with a total of 1 634 subjects. Two of the studies recruited adults, one children and 3 others recruited both adults and children. All patients were randomised within 2 weeks of their first seizure in 3 studies, and 70% of the patients were randomised within 2 months in one study. Three studies included only generalized tonic-clonic seizures and the others included both generalized and focal seizures. Patients were allocated to the intervention group (n = 816) and to the control group (n = 818), which was divided between deferred treatment (n = 606), placebo (n = 113), or no treatment (n = 99). For the two largest studies data were available for individual participant meta-analysis.

Compared to controls, participants randomised to immediate treatment had a lower probability of relapse at one year (RR 0.49, 95% CI 0.42 to 0.58; 6 studies, n = 1 634), at 5 years (RR 0.78, 95% CI 0.68 to 0.89; 2 studies, n = 1 212) and a higher probability of an immediate 5-year remission (RR 1.25, 95% CI 1.02 to 1.54; 2 studies, n = 1 212). However there was no difference between immediate treatment and control in terms of 5 year remission at any time (RR 1.02, 95% CI 0.87 to 1.21; 2 studies, n = 1 212). Antiepileptic drugs did not affect overall mortality after a first seizure (RR 1.16, 95% CI 0.69 to 1.95; 2 studies, n = 1 212). Compared to deferred treatment (RR 1.49, 95% CI 1.23 to 1.79; 2 studies, n = 1 212), treatment of the first seizure was associated with a significantly higher risk of adverse events. There was an association of adverse events and treatment of the first seizure vs. no treatment or placebo (RR 14.50, 95% CI 1.93 to 108.76; one study, n = 118) and (RR 4.91, 95% CI 1.10 to 21.93; one study, n = 228), respectively.

Clinical comments

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    References

    • Leone MA, Giussani G, Nevitt SJ et al. Immediate antiepileptic drug treatment, versus placebo, deferred, or no treatment for first unprovoked seizure. Cochrane Database Syst Rev 2021;(5):CD007144. [PubMed]

Primary/Secondary Keywords