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All applicable articles from <jats:styled-content style=\"fixed-case\">J<\/jats:styled-content>uly 2005 until <jats:styled-content style=\"fixed-case\">M<\/jats:styled-content>arch 2012 were identified, evaluated, and combined with the previous analysis (Glauser et al., 2006) to provide a comprehensive update. The prior analysis methodology was utilized with three modifications: (1) the detectable noninferiority boundary approach was dropped and both failed superiority studies and prespecified noninferiority studies were analyzed using a noninferiority approach, (2) the definition of an adequate comparator was clarified and now includes an absolute minimum point estimate for efficacy\/effectiveness, and (3) the relationship table between clinical trial ratings, level of evidence, and conclusions no longer includes a recommendation column to reinforce that this review of efficacy\/evidence for specific seizure types does not imply treatment recommendations. This evidence review contains one clarification: The commission has determined that class I superiority studies can be designed to detect up to a 20% absolute (rather than relative) difference in the point estimate of efficacy\/effectiveness between study treatment and comparator using an intent\u2010to\u2010treat analysis. Since <jats:styled-content style=\"fixed-case\">J<\/jats:styled-content>uly, 2005, three class I randomized controlled trials (<jats:styled-content style=\"fixed-case\">RCT<\/jats:styled-content>) and 11 class <jats:styled-content style=\"fixed-case\">III RCT<\/jats:styled-content>s have been published. The combined analysis (1940\u20132012) now includes a total of 64 <jats:styled-content style=\"fixed-case\">RCT<\/jats:styled-content>s (7 with class I evidence, 2 with class <jats:styled-content style=\"fixed-case\">II<\/jats:styled-content> evidence) and 11 meta\u2010analyses. New efficacy\/effectiveness findings include the following: levetiracetam and zonisamide have level <jats:styled-content style=\"fixed-case\">A<\/jats:styled-content> evidence in adults with partial onset seizures and both ethosuximide and valproic acid have level <jats:styled-content style=\"fixed-case\">A<\/jats:styled-content> evidence in children with childhood absence epilepsy. There are no major changes in the level of evidence for any other subgroup. Levetiracetam and zonisamide join carbamazepine and phenytoin with level <jats:styled-content style=\"fixed-case\">A<\/jats:styled-content> efficacy\/effectiveness evidence as initial monotherapy for adults with partial onset seizures. Although ethosuximide and valproic acid now have level <jats:styled-content style=\"fixed-case\">A<\/jats:styled-content> efficacy\/effectiveness evidence as initial monotherapy for children with absence seizures, there continues to be an alarming lack of well designed, properly conducted epilepsy <jats:styled-content style=\"fixed-case\">RCT<\/jats:styled-content>s for patients with generalized seizures\/epilepsies and in children in general. These findings reinforce the need for multicenter, multinational efforts to design, conduct, and analyze future clinically relevant adequately designed <jats:styled-content style=\"fixed-case\">RCT<\/jats:styled-content>s. When selecting a patient's <jats:styled-content style=\"fixed-case\">AED<\/jats:styled-content>, all relevant variables and not just efficacy and effectiveness should be considered.<\/jats:p>","DOI":"10.1111\/epi.12074","type":"journal-article","created":{"date-parts":[[2013,1,25]],"date-time":"2013-01-25T14:19:01Z","timestamp":1359123541000},"page":"551-563","source":"Crossref","is-referenced-by-count":641,"title":["Updated <scp>ILAE<\/scp> evidence review of antiepileptic drug efficacy and effectiveness as initial monotherapy for epileptic seizures and syndromes"],"prefix":"10.1111","volume":"54","author":[{"given":"Tracy","family":"Glauser","sequence":"first","affiliation":[{"name":"Comprehensive Epilepsy Center Division of Neurology Cincinnati Children's Hospital Medical Center University of Cincinnati College of Medicine Cincinnati Ohio U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elinor","family":"Ben\u2010Menachem","sequence":"additional","affiliation":[{"name":"Institution for Clinical Neuroscience Sahlgrenska Academy University of G\u00f6teborg G\u00f6teborg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blaise","family":"Bourgeois","sequence":"additional","affiliation":[{"name":"Department of Neurology The Children's Hospital and Harvard Medical School Boston Massachusetts U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avital","family":"Cnaan","sequence":"additional","affiliation":[{"name":"Division of Biostatistics and Study Methodology Center for Translational Science Children's National Medical Center Washington District of Columbia U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Guerreiro","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Campinas (UNICAMP) Hospital das Cl\u00ednicas Campinas Sao Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reetta","family":"K\u00e4lvi\u00e4inen","sequence":"additional","affiliation":[{"name":"Department of Neurology Kuopio Epilepsy Center Kuopio University Hospital Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Mattson","sequence":"additional","affiliation":[{"name":"Department of Neurology Yale University School of Medicine Yale New Haven Hospital New Haven Connecticut U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline A.","family":"French","sequence":"additional","affiliation":[{"name":"Comprehensive Epilepsy Center New York University Langone Medical Center New York New York U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilio","family":"Perucca","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Unit Institute of Neurology IRCCS C. 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