Alberto Verrotti1, Giovanni Prezioso2, Fabiana Di Sabatino2, Valentina Franco3, Francesco Chiarelli2, Gaetano Zaccara4. 1. Department of Pediatrics, University of Perugia, Perugia, Italy. Electronic address: averrott@unich.it. 2. Department of Pediatrics, University of Chieti, Chieti, Italy. 3. Clinical and Experimental Pharmacology Unit, Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy; C. Mondino National Neurological Institute, Pavia, Italy. 4. Unit of Neurology, Department of Medicine, Florence Health Authority, Firenze, Italy.
Abstract
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.
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.
Authors: Vincenzo Belcastro; Laura Rosa Pisani; Silvio Bellocchi; Paolo Casiraghi; Gaetano Gorgone; Marco Mula; Francesco Pisani Journal: J Neurol Date: 2017-03-18 Impact factor: 4.849
Authors: Andrew M Naidech; Jennifer Beaumont; Kathryn Muldoon; Eric M Liotta; Matthew B Maas; Matthew B Potts; Babak S Jahromi; David Cella; Shyam Prabhakaran; Jane L Holl Journal: Crit Care Med Date: 2018-09 Impact factor: 7.598
Authors: Diana C van Tuijl; Rolf H H Groenwold; Chantal Vlaskamp; Jolien S van Campen; Kees P J Braun; Floor E Jansen; Hilgo Bruining Journal: Epilepsia Open Date: 2017-01-18