- Design
- Systematic review and meta-analysis of randomised trials
- Population
- 8 trials, 1,000 children with new-onset or inadequately controlled epilepsy
- Primary outcome
- Seizure freedom
- Effect
- RR 0.95 (95% CI 0.83–1.09); low-certainty evidence
This meta-analysis pooled eight randomised trials, 1,000 children in all, comparing levetiracetam with valproate for new-onset epilepsy or epilepsy not controlled on previous treatment.
Seizure freedom did not differ significantly (5 trials, 655 children; RR 0.95, 95% CI 0.83–1.09), with moderate heterogeneity (I² 59.5%) and low-certainty evidence that was sensitive to a single trial. Exploratory analyses of time to seizure recurrence favoured valproate, but the authors note these handled censoring poorly. Levetiracetam was associated with fewer adverse events overall and less weight gain. Behavioural and hepatic safety comparisons remained uncertain.
For most children the choice between the two will rest on epilepsy type, sex and side-effect profile rather than expected efficacy. Valproate is effective in generalised epilepsies, but its teratogenicity makes it a poor choice for girls who may become pregnant, and levetiracetam's behavioural effects need watching.
- Choose between levetiracetam and valproate on epilepsy type and side-effects, not on expected seizure control.
- Avoid valproate in girls of childbearing potential unless other options have failed, under specialist advice.
- Ask about mood, irritability and behaviour at each review on levetiracetam.
- Monitor weight on valproate.
- Refer for specialist review if seizures are not controlled on the first drug.
Why it matters
Low-certainty evidence of equal efficacy puts the weight of the decision on harms — teratogenicity, weight and behaviour.
Don't overread it
The time-to-recurrence advantage for valproate came from exploratory analyses with methodological flaws.
The statistics, in plain English
An RR of 0.95 with an interval from 0.83 to 1.09 means seizure freedom could be up to 17% lower or 9% higher with levetiracetam. With I² near 60% and a result that changed when one trial was removed, the estimate is fragile.
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