{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T11:46:12Z","timestamp":1776426372356,"version":"3.51.2"},"reference-count":33,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2017,4,12]],"date-time":"2017-04-12T00:00:00Z","timestamp":1491955200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K23HD057333"],"award-info":[{"award-number":["K23HD057333"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["#HHSN271201100029C"],"award-info":[{"award-number":["#HHSN271201100029C"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2017,6]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Nonadherence to prescribed dosing regimens is a significant problem in the treatment of pediatric and adult chronic epilepsy, and can result in severe consequences to patient outcomes. In this first\u2010of\u2010kind preclinical study, the impact of nonadherence on seizure control was studied by simulating human patterns of nonadherence in an animal epilepsy model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In study 1, three different patterns of nonadherence were modeled in newly diagnosed epileptic rats treated with carbamazepine: perfect adherence (100% of pellets contained carbamazepine), variable nonadherence (50% of pellets contained carbamazepine with different dosing patterns between animals), and complete nonadherence (0% of pellets contained carbamazepine). In study 2, a cohort of newly diagnosed epileptic rats were subjected to a \u201cdrug holiday\u201d nonadherence paradigm, that is, a 2\u2010week on (100%), 2\u2010week off (0%), and 2\u2010week on (100%) carbamazepine paradigm.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the first experiment, the 100% (0.3\u00a0\u00b1\u00a00.2 SD convulsive seizures per day) adherent cohort demonstrated better seizure control than either the 0% (1.1\u00a0\u00b1\u00a00.8 SD) or 50% (0.8\u00a0\u00b1\u00a00.6 SD) adherent cohorts, which had similar levels of seizure control. In the second study, poor seizure control was exhibited during the second 2 weeks; that is, the drug holiday epoch; however, this did not negatively affect restoration of seizure control upon reinstatement of<jats:styled-content style=\"fixed-case\">CBZ<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>The results from this pilot investigation suggest that nonadherence to carbamazepine is associated with significant negative but reversible effects on seizure control in an animal model of epilepsy. Furthermore, these results demonstrate that animal studies of nonadherence can yield potentially important and translatable insights into the consequences of nonadherence on seizure control.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.13742","type":"journal-article","created":{"date-parts":[[2017,4,12]],"date-time":"2017-04-12T09:26:40Z","timestamp":1491989200000},"page":"1054-1062","source":"Crossref","is-referenced-by-count":29,"title":["The impact of nonadherence to antiseizure drugs on seizure outcomes in an animal model of epilepsy"],"prefix":"10.1111","volume":"58","author":[{"given":"Kyle E.","family":"Thomson","sequence":"first","affiliation":[{"name":"Department of Pharmacology &amp; Toxicology University of Utah Salt Lake City Utah U.S.A"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Avani C.","family":"Modi","sequence":"additional","affiliation":[{"name":"Cincinnati Children's Hospital Medical Center Cincinnati Ohio U.S.A"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tracy A.","family":"Glauser","sequence":"additional","affiliation":[{"name":"Cincinnati Children's Hospital Medical Center Cincinnati Ohio U.S.A"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph R.","family":"Rausch","sequence":"additional","affiliation":[{"name":"Cincinnati Children's Hospital Medical Center Cincinnati Ohio U.S.A"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H.","family":"Steve White","sequence":"additional","affiliation":[{"name":"Department of Pharmacology &amp; Toxicology University of Utah Salt Lake City Utah U.S.A"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,4,12]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2008.12.006"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2011.506"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1345\/aph.1P385"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2008.07.005"},{"key":"e_1_2_9_6_1","first-page":"150","article-title":"Non\u2010compliance with anticonvulsant therapy as a cause of seizures","volume":"98","author":"Stanaway L","year":"1985","journal-title":"N Z Med J"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000147"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000319693.10338.b9"},{"key":"e_1_2_9_9_1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1684\/j.1950-6945.2004.tb00043.x","article-title":"The mortality of epilepsy revisited","volume":"6","author":"Gaitatzis A","year":"2004","journal-title":"Epileptic Disord"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2012.09.008"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.12586"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2008.01794.x"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000147"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2010.02789.x"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2004.02.002"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.64.11.1595"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2014.09.019"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.12234"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2012.10.003"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.53.8.1736"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0920-1211(98)00017-5"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2011.03314.x"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2007.01263.x"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/0013-4694(72)90177-0"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-2236(00)01659-3"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.12341"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000001023"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1528-1157.2003.24203.x"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1053\/seiz.2000.0442"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0013-9580.2003.32803.x"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.43.11.2280"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0404.2005.00408.x"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/jpepsy\/jsv049"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1093\/jpepsy\/jsu010"}],"container-title":["Epilepsia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fepi.13742","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/epi.13742","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,23]],"date-time":"2024-06-23T14:56:38Z","timestamp":1719154598000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/epi.13742"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,4,12]]},"references-count":33,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2017,6]]}},"alternative-id":["10.1111\/epi.13742"],"URL":"https:\/\/doi.org\/10.1111\/epi.13742","archive":["Portico"],"relation":{},"ISSN":["0013-9580","1528-1167"],"issn-type":[{"value":"0013-9580","type":"print"},{"value":"1528-1167","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,4,12]]}}}