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

Seizure. 2014 Oct;23(9):685-91. doi: 10.1016/j.seizure.2014.06.004. Epub 2014 Jun 12.


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.

Keywords: Anti-epileptic drugs; Behavior; Behavioral problems; Children; Epilepsy; Levetiracetam.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Anticonvulsants / adverse effects*
  • Child
  • Child Behavior Disorders / chemically induced*
  • Databases, Bibliographic / statistics & numerical data
  • Epilepsy / drug therapy*
  • Humans
  • Levetiracetam
  • Piracetam / adverse effects
  • Piracetam / analogs & derivatives*


  • Anticonvulsants
  • Levetiracetam
  • Piracetam