{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T13:22:52Z","timestamp":1790256172175,"version":"4.1.0"},"reference-count":21,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2014,11,20]],"date-time":"2014-11-20T00:00:00Z","timestamp":1416441600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2014,12]]},"abstract":"Aim<\/jats:title>Epilepsy is a complex disease necessitating continuous development of new therapeutic strategies to encounter drug\u2010resistant cases. Among new adjuvant antiepileptic drugs, rufinamide is structurally distinct from other antiepileptic drugs. It is used to treat partial\u2010onset seizures and seizures associated with L<\/jats:styled-content>ennox\u2010G<\/jats:styled-content>astaut syndrome (LGS<\/jats:styled-content>) in adult and children. To date, there has been no attempt to evaluate systematically the risks of adverse events with rufinamide.<\/jats:p><\/jats:sec>Methods<\/jats:title>We performed a quantitative risk analysis of central nervous system (CNS<\/jats:styled-content>) adverse events of rufinamide from all randomized, double\u2010blind, add\u2010on, placebo\u2010controlled trials. The meta\u2010analysis was undertaken with fixed effects models.<\/jats:p><\/jats:sec>Results<\/jats:title>Of the 886 publications reviewed, 99 papers were retrieved and five articles met the inclusion criteria. One thousand two hundred and fifty\u2010two patients were included. Our study showed that exposure to rufinamide was associated with a significant increase in risk of somnolence [relative ratio (RR<\/jats:styled-content>) 1.87; 95% confidence interval (CI<\/jats:styled-content>) 1.33, 2.62; P<\/jats:italic> = 0.0003], dizziness (RR<\/jats:styled-content> 2.66; 95% CI<\/jats:styled-content> 2.00, 3.55; P<\/jats:italic> = 0.00001), fatigue (RR<\/jats:styled-content> 2.14; 95% CI<\/jats:styled-content> 1.57, 2.91; P<\/jats:italic> = 0.01) and headache (RR<\/jats:styled-content> 1.28; 95% CI<\/jats:styled-content> 1.02, 1.59, P<\/jats:italic> = 0.03). In addition, exposure to rufinamide was associated with higher treatment discontinuation rates as compared with placebo (RR<\/jats:styled-content> 2.65; 95% CI<\/jats:styled-content> 1.74, 4.03; P<\/jats:italic> = 0.00001).<\/jats:p><\/jats:sec>Conclusions<\/jats:title>The risk of CNS<\/jats:styled-content> adverse events appears to be increased in patients exposed to rufinamide as well as the treatment discontinuation rates. However, although statistical associations were significant, additional long term safety studies are required to confirm the clinical significance of these findings, as most reports described only mild and moderate adverse events.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.12479","type":"journal-article","created":{"date-parts":[[2014,8,5]],"date-time":"2014-08-05T10:16:50Z","timestamp":1407233810000},"page":"1264-1271","source":"Crossref","is-referenced-by-count":14,"title":["Exposure to rufinamide and risks of CNS<\/scp> adverse events in drug\u2010resistant epilepsy: a meta\u2010analysis of randomized, placebo\u2010controlled trials"],"prefix":"10.1111","volume":"78","author":[{"given":"Abdulaziz M. S.","family":"Alsaad","sequence":"first","affiliation":[{"name":"Motherisk Program Division of Clinical Pharmacology and Toxicology Department of Pediatrics Hospital for Sick Children and University of Toronto Toronto ON"},{"name":"Leslie Dan Faculty of Pharmacy University of Toronto Toronto ON Canada"},{"name":"Department of Pharmacology & Toxicology College of Pharmacy King Saud University Riyadh KSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gideon","family":"Koren","sequence":"additional","affiliation":[{"name":"Motherisk Program Division of Clinical Pharmacology and Toxicology Department of Pediatrics Hospital for Sick Children and University of Toronto Toronto ON"},{"name":"Leslie Dan Faculty of Pharmacy University of Toronto Toronto ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,11,20]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200002033420503"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2007.00992.x"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.2147\/nedt.2007.3.1.3"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2010.10.017"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000303813.95800.0d"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2010.12.005"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2006.07.001"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2008.01665.x"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2006.00589.x"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2009.02160.x"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2010.02729.x"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1177\/0883073809350508"},{"key":"e_1_2_9_14_1","volume-title":"Review Manager (RevMan) [Computer Program]","author":"RevMan","year":"2012"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2009.12.003"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0920-1211(00)00185-6"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0404.2010.01334.x"},{"key":"e_1_2_9_18_1","volume-title":"Eisai Data on File: Study E2080\u2010A001\u2010001. 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