The adverse event profile of levetiracetam: A meta-analysis on children and adults.

PURPOSE: To analyze the adverse events (AEs) significantly associated with levetiracetam (LEV) therapy through a meta-analysis of all available double-blind, randomized placebo-controlled trials (RCTs), performed in any age, gender, ethnic background and disease. General tolerability and study withdrawals due to AEs associated with LEV treatment were also investigated. In addition, a dose-effect responses relationship for all variables was assessed. METHODS: RCTs were identified searching Medline (PubMed), Embase and Cochrane CENTRAL for the words "Levetiracetam" and "randomized controlled trial", with different search strategies, setting the limits "humans" and "English". Very common and common AEs according to the summary of product characteristics were investigated. RevMan version 5.2 was used for the statistical analyses. Risk difference with 95% confidence intervals was used to investigate the association of any AEs and withdrawal with LEV. RESULTS: Twenty-six studies with 2832 patients were included in the RCTs analysis. Nasopharyngitis, somnolence, dizziness, nervousness/irritability and asthenia/fatigue were statistically significant associated with LEV. In addition, LEV was significantly associated with an increased risk of AEs-related withdrawals. No dose-response relationship was found for any of the assessed variables. CONCLUSIONS: This first large meta-analysis suggests that participants were more likely to discontinue LEV than placebo. The AE profile confirmed that LEV is associated with few unfavorable sedative, vestibulocerebellar and behavioral effects, such as nervousness and irritability. However, there does not seem to be a clear dose-response relationship.