{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T07:45:07Z","timestamp":1781509507668,"version":"3.54.1"},"reference-count":73,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,12,22]],"date-time":"2017-12-22T00:00:00Z","timestamp":1513900800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100011102","name":"Seventh Framework Programme","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011102","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2018,2]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To estimate the comparative efficacy among antiepileptic drugs in the pediatric population (0\u201018 years).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using the<jats:styled-content style=\"fixed-case\"> Embase<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">MEDLINE<\/jats:styled-content> databases, we updated to February 2017 the search strategy of the National Institute for Health and Care Excellence guidelines for epilepsy. We only included randomized clinical trials conducted in children and mixed\u2010age populations. According to the <jats:styled-content style=\"fixed-case\">PRISMA<\/jats:styled-content> network meta\u2010analysis guideline, the study\u2010level quality assessment was made with the Cochrane risk\u2010of\u2010bias tool. Three investigators independently selected articles. The efficacy outcome was considered to be seizure freedom or \u226550% seizure reduction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We selected 46 randomized clinical trials. A total of 5652 individuals were randomized to 22 antiepileptic drugs and placebo. The point estimates of carbamazepine and lamotrigine efficacy showed their superiority with respect to all comparator antiepileptic drugs for the treatment of newly diagnosed focal epilepsy. In refractory focal epilepsy, levetiracetam (odds ratio [<jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content>] = 3.3, 95% credible interval [CrI] = 1.3\u20107.6) and perampanel (<jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content> = 2.5, 95% CrI = 1.1\u20105.8) were more effective compared to placebo. Ethosuximide and valproic acid were both superior to lamotrigine against absence seizures. The <jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content> point estimate showed the superiority of adrenocorticotropic hormone over all comparators in infantile spasms. A wide heterogeneity in the length of follow\u2010up was observed among the studies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>This network meta\u2010analysis suggests that the quality of studies should be improved through the use of comparative designs, relevant outcomes, appropriate follow\u2010up length, and more reliable inclusion criteria.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.13981","type":"journal-article","created":{"date-parts":[[2017,12,24]],"date-time":"2017-12-24T05:14:01Z","timestamp":1514092441000},"page":"297-314","source":"Crossref","is-referenced-by-count":39,"title":["Comparative efficacy of antiepileptic drugs in children and adolescents: A network meta\u2010analysis"],"prefix":"10.1111","volume":"59","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8754-7214","authenticated-orcid":false,"given":"Anna","family":"Rosati","sequence":"first","affiliation":[{"name":"Neuroscience Center of Excellence Meyer Children's Hospital University of Florence Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucrezia","family":"Ilvento","sequence":"additional","affiliation":[{"name":"Neuroscience Center of Excellence Meyer Children's Hospital University of Florence Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ersilia","family":"Lucenteforte","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Psychology, Drug Research, and Child Health University of Florence Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Pugi","sequence":"additional","affiliation":[{"name":"Clinical Trial Office Meyer Children's Hospital Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giada","family":"Crescioli","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Psychology, Drug Research, and Child Health University of Florence Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen S.","family":"McGreevy","sequence":"additional","affiliation":[{"name":"Research, Innovation, and International Relations Office Meyer Children's Hospital Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianni","family":"Virgili","sequence":"additional","affiliation":[{"name":"Department of Surgery and Translational Medicine University of Florence Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Mugelli","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Psychology, Drug Research, and Child Health University of Florence Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore","family":"De Masi","sequence":"additional","affiliation":[{"name":"Clinical Trial Office Meyer Children's Hospital Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renzo","family":"Guerrini","sequence":"additional","affiliation":[{"name":"Neuroscience Center of Excellence Meyer Children's Hospital University of Florence Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,12,22]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2010.02522.x"},{"key":"e_1_2_8_3_1","unstructured":"European Medicines Agency. Committee for Medicinal Products for Human Use. Guideline on clinical investigation of medicinal products in the treatment of epileptic disorders. July 22 2010. Available athttp:\/\/www.ema.europa.eu\/docs\/en_GB\/document_library\/Scientific_guideline\/2010\/01\/WC500070043.pdfAccessed December 11 2017."},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.5863\/1551-6776-21.1.98"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.12179"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(06)68182-8"},{"key":"e_1_2_8_7_1","volume-title":"The diagnosis and management of the epilepsies in adults and children in primary and secondary care","author":"The Epilepsies"},{"key":"e_1_2_8_8_1","unstructured":"The Cochrane Collaboration.Cochrane handbook for systematic reviews of interventions (version 5.1.0). March 2011. Available athttp:\/\/handbookcochrane.orgAccessed September 15 2016."},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.1875"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.1201"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/jrsm.1054"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11222-011-9281-9"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-21416-0"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2011.04.005"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0920-1211(97)00025-9"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-8749.1995.tb11978.x"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(96)90074-4"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2012.03.006"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0920-1211(01)00271-6"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.1999.tb00833.x"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.52.7.1338"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.53.8.1724"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.54.12.2237"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000217916.00225.3a"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.12233"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181d1cd4c"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2008.01981.x"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpn.2015.02.008"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13417"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2006.09.008"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.2000.tb04606.x"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-8749.1982.tb13703.x"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0013-9580.2004.40903.x"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2010.02976.x"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.12028"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.32.2.157"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2007.03.003"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jocn.2012.10.020"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.1999.tb02049.x"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.97.3.375"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2014.06.019"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1986.00520110007005"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1177\/0883073810365103"},{"key":"e_1_2_8_44_1","first-page":"12","article-title":"Randomised clinical efficacy trial of topiramate and nitrazepam in treatment of infantile spasms","volume":"8","author":"Fallah R","year":"2014","journal-title":"Iran J Child Neurol"},{"key":"e_1_2_8_45_1","first-page":"18","article-title":"Vigabatrin versus ACTH in the treatment of infantile spasms","volume":"7","author":"Omar FZ","year":"2002","journal-title":"Neurosciences (Riyadh)"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(83)80606-4"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)17400-X"},{"key":"e_1_2_8_48_1","first-page":"143","article-title":"Ineffectiveness of topiramate and levetiracetam in infantile spasms non\u2010responsive to steroids. Open labeled randomized prospective study","volume":"18","author":"Mahmoud AA","year":"2013","journal-title":"Neurosciences (Riyadh)"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.1997.tb00063.x"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2010.04.008"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2015.05.004"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(16)30294-0"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000303813.95800.0d"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199712183372504"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2014.08.019"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e318232de76"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.52.9.1882"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199301073280105"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(00)03157-3"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.j3932"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)60460-7"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.1990.tb05522.x"},{"key":"e_1_2_8_63_1","first-page":"CD003032","article-title":"Ethosuximide, sodium valproate or lamotrigine for absence seizures in children and adolescents","volume":"2","author":"Brigo F","year":"2017","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_8_64_1","unstructured":"European Medicines Agency. Pharmacovigilance Risk Assessment Committee (PRAC). Assessment report:substances related to valproate.October 9 2014. Available athttp:\/\/www.ema.europa.eu\/docs\/en_GB\/document_library\/Referrals_document\/Valproate_and_related_substances_31\/Recommendation_provided_by_Pharmacovigilance_Risk_Assessment_Committee\/WC500177352.pdfAccessed December 11 2017."},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000297512.18364.40"},{"key":"e_1_2_8_66_1","first-page":"CD010483","article-title":"Antiepileptic drugs for the treatment of infants with severe myoclonic epilepsy","volume":"5","author":"Brigo F","year":"2017","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(15)00379-8"},{"key":"e_1_2_8_68_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13407"},{"key":"e_1_2_8_69_1","first-page":"CD011412","article-title":"Antiepileptic drug monotherapy for epilepsy: a network meta\u2010analysis of individual participant data","volume":"6","author":"Nevitt SJ","year":"2017","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_8_70_1","doi-asserted-by":"publisher","DOI":"10.1002\/phar.1855"},{"key":"e_1_2_8_71_1","unstructured":"European Medicines Agency. Human Medicines Development and Evaluation. Concept paper on extrapolation of efficacy and safety in medicine development. June 22 2012. Available athttp:\/\/www.ema.europa.eu\/docs\/en_GB\/document_library\/Scientific_guideline\/2012\/06\/WC500129285.pdfAccessed December 11 2017."},{"key":"e_1_2_8_72_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2010-3487"},{"key":"e_1_2_8_73_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13859"},{"key":"e_1_2_8_74_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e31826d5ec0"}],"container-title":["Epilepsia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fepi.13981","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/epi.13981","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,23]],"date-time":"2023-09-23T22:31:12Z","timestamp":1695508272000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/epi.13981"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,12,22]]},"references-count":73,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2018,2]]}},"alternative-id":["10.1111\/epi.13981"],"URL":"https:\/\/doi.org\/10.1111\/epi.13981","archive":["Portico"],"relation":{},"ISSN":["0013-9580","1528-1167"],"issn-type":[{"value":"0013-9580","type":"print"},{"value":"1528-1167","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,12,22]]}}}