{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T12:42:39Z","timestamp":1792154559437,"version":"4.4.0"},"reference-count":26,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2021,7,15]],"date-time":"2021-07-15T00:00:00Z","timestamp":1626307200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>We conducted a post hoc analysis of two randomized controlled trials, GWPCARE1 (NCT02091375) and GWPCARE2 (NCT02224703), to estimate the time to onset of cannabidiol (CBD) treatment effects (seizure reduction and adverse events [AEs]) in patients with Dravet syndrome (DS).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients received either plant\u2010derived highly purified CBD (Epidiolex in the United States; 100\u00a0mg\/ml oral solution) 10\u00a0mg\/kg\/day (CBD10; GWPCARE2) or 20\u00a0mg\/kg\/day (CBD20; GWPCARE1&amp;2), or matching placebo for 14\u00a0weeks. Treatment started at 2.5\u00a0mg\/kg\/day, reached 10\u00a0mg\/kg\/day on Day 7, and went up to 20\u00a0mg\/kg\/day on Day 11 during the 14\u2010day titration period. Percentage change from baseline in convulsive seizure frequency was calculated by cumulative day (i.e., including all previous days). Time to onset and resolution of AEs were also evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Overall, 124 patients received placebo and 194 received CBD (CBD10,<jats:italic>n<\/jats:italic>\u00a0=\u00a064; CBD20,<jats:italic>n<\/jats:italic>\u00a0=\u00a0130). Mean age was 9.5\u00a0years (range = 2.2\u201318.9). Patients had discontinued a median of four antiepileptic drugs (range = 0\u201326) and were currently taking a median of three (range = 1\u20135). Differences in convulsive seizure reduction between placebo and CBD emerged during titration and became nominally significant by Day 12 for CBD20 (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.02) and Day 13 for CBD10 (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.03). Additionally, differences in the 50% responder rate between placebo and CBD became apparent during titration. Onset of the first reported AE occurred during the titration period in 48.4% of placebo patients and 54.1% of CBD patients. The three most common AEs of somnolence, decreased appetite, and diarrhea resolved within 4 weeks of onset in the majority of CBD\u2010treated patients (56.3%\u201372.9%).<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>The therapeutic effect of CBD in DS may start within 2 weeks of treatment in some patients. Although AEs lasted longer for CBD than placebo, most resolved within the 14\u2010week study period.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.16974","type":"journal-article","created":{"date-parts":[[2021,7,15]],"date-time":"2021-07-15T19:49:33Z","timestamp":1626378573000},"page":"2218-2227","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Time to onset of cannabidiol treatment effects in Dravet syndrome: Analysis from two randomized controlled trials"],"prefix":"10.1111","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7087-1448","authenticated-orcid":false,"given":"Jennifer","family":"Madan Cohen","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Division of Neurology at Connecticut Children\u2019s University of Connecticut Hartford Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Checketts","sequence":"additional","affiliation":[{"name":"GW Research Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo","family":"Dunayevich","sequence":"additional","affiliation":[{"name":"Greenwich Biosciences Carlsbad California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boudewijn","family":"Gunning","sequence":"additional","affiliation":[{"name":"Stichting Epilepsie Instellingen Nederland Zwolle the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann","family":"Hyslop","sequence":"additional","affiliation":[{"name":"Nicklaus Children\u2019s Hospital Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepak","family":"Madhavan","sequence":"additional","affiliation":[{"name":"Boys Town National Research Hospital Boys Town Nebraska USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vicente","family":"Villanueva","sequence":"additional","affiliation":[{"name":"University and Polytechnic Hospital La Fe Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Zolnowska","sequence":"additional","affiliation":[{"name":"Medical Center Plejady Krakow Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sameer M.","family":"Zuberi","sequence":"additional","affiliation":[{"name":"Paediatric Neurosciences Research Group Royal Hospital for Children &amp; College of Medical, Veterinary, and Life Sciences University of Glasgow Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,7,15]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2011.02994.x"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13709"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/0883073807304207"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2006.00688.x"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awz195"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2017.01.025"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.4414\/sanp.2013.00174"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2011.03007.x"},{"key":"e_1_2_9_10_1","volume-title":"EPIDIOLEX (cannabidiol) oral solution [full prescribing information]","year":"2020"},{"key":"e_1_2_9_11_1","volume-title":"Epidyolex (cannabidiol) oral solution [summary of product characteristics]","year":"2019"},{"key":"e_1_2_9_12_1","volume-title":"DIACOMIT (stiripentol) capsules, powder for oral solution [full prescribing information]","year":"2018"},{"key":"e_1_2_9_13_1","volume-title":"FINTEPLA (fenfluramine) oral solution, CIV [full prescribing information]","year":"2020"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1017\/cjn.2016.249"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1611618"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2020.0073"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1714631"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)30136-3"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2020.4607"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.14628"},{"key":"e_1_2_9_21_1","doi-asserted-by":"crossref","unstructured":"SchefferIE HalfordJJ NabboutR Sanchez\u2010CarpinteroR Shiloh\u2010MalawksyY WongM et al.Long\u2010term safety and efficacy of add\u2010on cannabidiol in patients with Dravet syndrome: 3\u2010year results of an open\u2010label extension trial (GWPCARE5). AES 2019 Annual Meeting Abstract Database.https:\/\/cms.aesnet.org\/abstractslisting\/long\u2010term\u2010safety\u2010and\u2010efficacy\u2010of\u2010add\u2010on\u2010cannabidiol\u2010(cbd)\u2010treatment\u2010in\u2010patients\u2010with\u2010dravet\u2010syndrome\u2010(ds)\u2010\u20103\u2010year\u2010results\u2010of\u2010an\u2010open\u2010label\u2010extension\u2010(ole)\u2010trial\u2010(gwpcare5). 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