{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T10:56:02Z","timestamp":1791024962465,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T00:00:00Z","timestamp":1790985600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T00:00:00Z","timestamp":1790985600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epileptic Disorders"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Antiseizure medications (ASMs) can reduce the efficacy of statin treatment, partly due to reduction in statin concentrations. In this systematic review and network meta\u2010analysis (NMA), we compared the effects of ASMs and the prototypical enzyme inducer rifampin on statin exposure.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The study was registered in PROSPERO (CRD42024622109) and followed the PRISMA 2015\/2020 guidelines. Searches through January 19, 2026, were conducted in MEDLINE, EMBASE, the Cochrane Library, and the FDA database. We included prospective studies in which ASMs or rifampin were administered for \u2265\u20095\u2009days. The primary endpoint was the area under the concentration\u2010time curve ratio (AUCR) of the statin with\/without the perpetrator. Perpetrator\u2010statin combinations were compared pairwise using the standardized mean difference (SMD). The PKclin tool was used for assessing the bias risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The NMA included six studies with 236 participants, of which four (206 participants) assessed four ASMs. The AUCR of simvastatin after exposure to 800\u2009mg\/day eslicarbazepine (mean 0.460; 90% confidence interval, 0.378\u20130.561) was comparable to those of the combinations 200\u2013400\u2009mg\/day phenytoin\u2013atorvastatin (0.463; 0.385\u20130.556), 600\u2009mg\/day carbamazepine\u2013pravastatin (0.382; 0.321\u20130.455) or \u2013rosuvastatin (0.388; 0.353\u20130.427), and 600\u2009mg\/day rifampin\u2013rosuvastatin (0.371; 0.317\u20130.435), but lower than with 1200\u2009mg\/day eslicarbazepine\u2013rosuvastatin (0.630; 0.571\u20130.694). Similarly, in the NMA, the effect of 800\u2009mg\/day eslicarbazepine on simvastatin did not differ from those of rifampin on pravastatin\/rosuvastatin (SMD 0.08, confidence interval, \u22120.03 to 0.19) or phenytoin on atorvastatin (0.00; \u22120.14 to 0.14).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>Despite the limited number of studies and methodological variation, our analysis demonstrates that all statins can be considerably affected by strong enzyme\u2010inducing ASMs. The effects of ASMs with moderate enzyme\u2010inducing activity on simvastatin, lovastatin, and atorvastatin are comparable to those of strong inducers on pravastatin or rosuvastatin. Careful selection of ASM\u2010statin combinations with appropriate monitoring can improve patient outcomes, and co\u2010medication reporting in clinical trials can help interpretation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epd2.70416","type":"journal-article","created":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T10:49:57Z","timestamp":1791024597000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The effect of anti\u2010seizure medications on exposure to statins: A systematic review and meta\u2010analysis"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-7297-4089","authenticated-orcid":false,"given":"Sharon Valiyev","family":"Huino","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy, Faculty of Medicine, School of Pharmacy Hebrew University of Jerusalem  Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0461-4272","authenticated-orcid":false,"given":"Hagar","family":"Cohen","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, Faculty of Medicine, School of Pharmacy Hebrew University of Jerusalem  Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9670-9134","authenticated-orcid":false,"given":"Bruria Hirsh","family":"Raccah","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, Faculty of Medicine, School of Pharmacy Hebrew University of Jerusalem  Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0415-566X","authenticated-orcid":false,"given":"Tomer","family":"Ben\u2010Shushan","sequence":"additional","affiliation":[{"name":"Medical Library Authority The Hebrew University of Jerusalem  Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1559-9258","authenticated-orcid":false,"given":"Ilan","family":"Matok","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, Faculty of Medicine, School of Pharmacy Hebrew University of Jerusalem  Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1275-6094","authenticated-orcid":false,"given":"Sara","family":"Eyal","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, Faculty of Medicine, School of Pharmacy Hebrew University of Jerusalem  Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,3]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.atherosclerosis.2025.120479","article-title":"2025 Focused update of the 2019 ESC\/EAS guidelines for the management of dyslipidaemias","volume":"409","author":"Mach F","year":"2025","journal-title":"Atherosclerosis"},{"issue":"32","key":"e_1_2_10_3_1","doi-asserted-by":"crossref","first-page":"2459","DOI":"10.1093\/eurheartj\/ehx144","article-title":"Low\u2010density lipoproteins cause atherosclerotic cardiovascular disease. 1. 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