Behavioral side-effects of levetiracetam in children with epilepsy: A systematic review

Elisabeth Halma, Anton J. A. de Louw*, Sylvia Klinkenberg, Albert P. Aldenkamp, Dominique M. IJff, Marian Majoie

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Purpose: Children with epilepsy are more likely to have behavioral problems compared to children without epilepsy. Literature suggests that levetiracetam leads to behavioral side-effects in children with epilepsy. The objective of this study is to provide a better overview of the frequency and variety of behavioral side-effects, which can be initiated by levetiracetam therapy in children with epilepsy. Method: Electronic databases used in the search were PubMed, Medline, Cochrane and Embase. Studies were eligible for inclusion when they included children from one month to 18 years of age with a diagnosis of epilepsy, used levetiracetam, had other AEDs on a stable regimen for at least two months, reported about behavioral side-effects and had a follow-up of at least two weeks. Quality assessments and data collection were carried out for all eligible studies. Results: Thirteen studies, including 727 patients using levetiracetam, were included in this systematic review. Three randomized controlled trials showed a total of 62 behavioral side-effects in 203 patients, effects which led to discontinuation of levetiracetam in only two of 102 patients (2.0%). Hostility, nervousness and aggression were reported mostly. Meta-analysis showed a statistically significant relative risk of 2.18 for the total number of behavioral side-effects for levetiracetam versus placebo. Observational studies showed mixed results with both behavioral deteriorations and improvements following levetiracetam. Conclusion: Based on the findings in this systematic review, children using levetiracetam have a risk of developing several behavioral side-effects such as aggression, hostility and nervousness compared to children who do not use levetiracetam.
Original languageEnglish
Pages (from-to)685-691
Issue number9
Publication statusPublished - Oct 2014


  • Anti-epileptic drugs
  • Levetiracetam
  • Epilepsy
  • Children
  • Behavioral problems
  • Behavior


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