eprintid: 10052454 rev_number: 26 eprint_status: archive userid: 608 dir: disk0/10/05/24/54 datestamp: 2018-11-15 09:46:40 lastmod: 2021-09-26 22:09:59 status_changed: 2018-11-15 09:46:40 type: article metadata_visibility: show creators_name: Shorvon, SD creators_name: Bermejo, PE creators_name: Gibbs, AA creators_name: Huberfeld, G creators_name: Kalviainen, R title: Antiepileptic drug treatment of generalized tonic-clonic seizures: An evaluation of regulatory data and five criteria for drug selection ispublished: pub subjects: UCH divisions: UCL divisions: B02 divisions: C07 divisions: D07 divisions: F85 keywords: Antiepileptic drugs, Generalized seizures, Efficacy, Tonic–clonic seizures, Adverse events note: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. abstract: BACKGROUND: A generalized tonic–clonic seizure (GTCS) is the most severe form of common epileptic seizure and carries the greatest risk of harm. The aim of this review is to provide an evidence-based guide for the selection of antiepileptic drugs (AEDs) for patients with GTCSs. Eight AEDs are approved in Europe and the USA for the treatment of both primarily GTCSs (PGTCSs) and secondarily GTCSs (SGTCSs) and are considered in this paper. METHODS: Each AED is evaluated using five criteria: (1) efficacy, by seizure type (a: PGTCSs and b: SGTCSs); (2) adverse effects; (3) interactions; (4) adherence and dosing; and (5) mechanism of action (MOA). To ensure the inclusions of robust data, only efficacy data accepted by regulatory authorities were considered, and data related to adverse effects, interactions, adherence, and MOA were all extracted from UK Summaries of Product Characteristics (SPCs). RESULTS: (1a) There is class 1 evidence of the efficacy of only four AEDs in controlling PGTCSs (lamotrigine, levetiracetam, perampanel, and topiramate). (1b) There is no class 1 evidence of the efficacy of any AED in SGTCSs although some evidence from pooled/subgroup analyses or meta-analyses supports the use of the four AEDs (levetiracetam, perampanel, topiramate, and with less robust data for lamotrigine). (2) AEDs are associated with different, but to some extent overlapping, common adverse effect profiles but have differing idiosyncratic adverse effects. (3) Pharmacokinetic interactions are seen with most, but not all, AEDs and are most common with carbamazepine and phenytoin. (4) Good adherence is important for seizure control and is influenced by frequency of dosing, among other factors. (5) Mechanism of action is also a consideration in rationalising AED selection when switching or combining AEDs. CONCLUSION: Ultimately, the choice of AED depends on all these factors but particularly on efficacy and adverse effects. Different patients will weigh the various factors differently, and the role of the treating physician is to provide accurate information to allow patients to make informed choices. date: 2018-05 date_type: published publisher: ACADEMIC PRESS INC ELSEVIER SCIENCE official_url: https://doi.org/10.1016/j.yebeh.2018.01.039 oa_status: green full_text_type: other language: eng primo: open primo_central: open_green article_type_text: Review verified: verified_manual elements_id: 1547279 doi: 10.1016/j.yebeh.2018.01.039 language_elements: English lyricists_name: Shorvon, Simon lyricists_id: SDSHO52 actors_name: Novi, Maya actors_id: MNOVI52 actors_role: owner full_text_status: public publication: Epilepsy & Behavior volume: 82 pagerange: 91-103 pages: 13 issn: 1525-5069 citation: Shorvon, SD; Bermejo, PE; Gibbs, AA; Huberfeld, G; Kalviainen, R; (2018) Antiepileptic drug treatment of generalized tonic-clonic seizures: An evaluation of regulatory data and five criteria for drug selection. Epilepsy & Behavior , 82 pp. 91-103. 10.1016/j.yebeh.2018.01.039 <https://doi.org/10.1016/j.yebeh.2018.01.039>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10052454/3/Shorvon_R2%20-%20AEDs%20for%20TCS%20Manuscript%20for%20E%2526B_by%20email.pdf