{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T16:36:04Z","timestamp":1784306164165,"version":"3.55.0"},"reference-count":21,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,8,1]],"date-time":"2024-08-01T00:00:00Z","timestamp":1722470400000},"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 Open"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>The cannabidiol (CBD) Expanded Access Program provided compassionate access to CBD for patients with treatment\u2010resistant epilepsy, including tuberous sclerosis complex (TSC), at 35 US epilepsy centers. Here, we present the long\u2010term efficacy and safety outcomes for add\u2010on CBD treatment in patients with TSC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients received plant\u2010derived, highly purified CBD (Epidiolex\u00ae 100\u2009mg\/mL, oral solution), increasing from 2 to 10\u2009mg\/kg\/d to tolerance or maximum of 25\u201350\u2009mg\/kg\/d. Efficacy endpoints were percentage change from baseline in median monthly convulsive, focal, and total seizure frequency and\u2009\u2265\u200950%, \u226575%, and 100% responder rates across 12\u2010week visit windows through 144\u2009weeks. Adverse events (AEs) are reported through 233\u2009weeks.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Thirty\u2010four patients with confirmed TSC were included. Mean age was 12.4\u2009years (range, 1.8\u201331.2), and patients were receiving a median of 3 (range, 1\u20137) antiseizure medications (ASMs) at baseline. Median CBD dose was 25\u201328\u2009mg\/kg\/d for 36\u2009weeks and then 20\u201350\u2009mg\/kg\/d through 228\u2009weeks. Dose reduction from baseline occurred for most ASMs, except topiramate. Median reduction in the frequency of convulsive, focal, and total seizures was 44%\u201381%, 51%\u201387%, and 44%\u201387%, respectively, through 144\u2009weeks. Responder rates (\u226550%, \u226575%, and 100% reduction) were 43%\u201371%, 14%\u201358%, and 0%\u201325% for convulsive seizures; 52%\u201375%, 35%\u201360%, and 7%\u201332% for focal seizures; and 46%\u201379%, 26%\u201365%, and 0%\u201313% for total seizures. A total of 94% of patients experienced \u22651 AE; 47% had serious AEs, considered treatment unrelated by the investigator. Treatment\u2010related AEs (TRAEs) occurred in 71% of patients. The most frequently reported TRAEs were somnolence, diarrhea, and ataxia. Two patients experienced AEs leading to discontinuation. There were no deaths.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Long\u2010term add\u2010on CBD use was associated with reduced seizure frequency through 144\u2009weeks. The safety profile was consistent with previous reports.<\/jats:p><\/jats:sec><jats:sec><jats:title>Plain Language Summary<\/jats:title><jats:p>In this study, we evaluated efficacy and safety of cannabidiol (CBD) treatment in patients with tuberous sclerosis complex receiving CBD in addition to other antiseizure treatments in an Expanded Access Program. After starting CBD, 46%\u201379% of patients had at least 50% reduction and 26%\u201365% had at least 75% reduction in the number of seizures per month; up to 13% had no seizures through 144\u2009weeks. Safety results were similar to prior studies; sleepiness and diarrhea were common treatment\u2010related side effects. These results show that long\u2010term CBD treatment was associated with fewer seizures and mild\/moderate side effects.<\/jats:p><\/jats:sec>","DOI":"10.1002\/epi4.13013","type":"journal-article","created":{"date-parts":[[2024,8,1]],"date-time":"2024-08-01T15:16:43Z","timestamp":1722525403000},"page":"1816-1825","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Long\u2010term efficacy and safety of cannabidiol in patients with tuberous sclerosis complex: 3\u2010year results from the cannabidiol expanded access program"],"prefix":"10.1002","volume":"9","author":[{"given":"Arie","family":"Weinstock","sequence":"first","affiliation":[{"name":"University at Buffalo\/Oishei Children's Hospital  Buffalo New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1264-3428","authenticated-orcid":false,"given":"E. Martina","family":"Bebin","sequence":"additional","affiliation":[{"name":"University of Alabama Birmingham  Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Checketts","sequence":"additional","affiliation":[{"name":"Jazz Pharmaceuticals, Inc  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary D.","family":"Clark","sequence":"additional","affiliation":[{"name":"Texas Children's Hospital\/Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5936-6627","authenticated-orcid":false,"given":"Jerzy P.","family":"Szaflarski","sequence":"additional","affiliation":[{"name":"University of Alabama Birmingham  Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurie E.","family":"Seltzer","sequence":"additional","affiliation":[{"name":"University of Rochester Medical Center  Rochester New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3431-4713","authenticated-orcid":false,"given":"Elizabeth A.","family":"Thiele","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farhad","family":"Sahebkar","sequence":"additional","affiliation":[{"name":"Jazz Pharmaceuticals, Inc  Carlsbad California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,8]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13499"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genom-083118-015354"},{"key":"e_1_2_12_4_1","unstructured":"NORD.Tuberous sclerosis. Available from:https:\/\/rarediseases.org\/rare\u2010diseases\/tuberous\u2010sclerosis\/. Accessed September 6 2023"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-016-0553-5"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13467"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2021.07.011"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2009.02474.x"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-018-0901-8"},{"key":"e_1_2_12_10_1","unstructured":"The U.S. Food and Drug Administration.EPIDIOLEX\u00ae Prescribing Information.2023[cited 2023 Dec 11]. Available from:https:\/\/www.epidiolex.com\/sites\/default\/files\/pdfs\/1120\/EPX\u201003645\u20101120_EPIDIOLEX_(cannabidiol)_USPI.pdf. Accessed December 11 2023 2023"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1611618"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1714631"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2020.0073"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2020.4607"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)30136-3"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17000"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17036"},{"key":"e_1_2_12_18_1","volume-title":"Presented at American Epilepsy Society 2022 annual meeting","author":"Thiele E","year":"2022"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17496"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.14477"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17150"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.16674"}],"container-title":["Epilepsia Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/epi4.13013","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T10:25:59Z","timestamp":1741775159000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/epi4.13013"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8]]},"references-count":21,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2024,10]]}},"alternative-id":["10.1002\/epi4.13013"],"URL":"https:\/\/doi.org\/10.1002\/epi4.13013","archive":["Portico"],"relation":{},"ISSN":["2470-9239","2470-9239"],"issn-type":[{"value":"2470-9239","type":"print"},{"value":"2470-9239","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8]]},"assertion":[{"value":"2024-03-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-07-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-08-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}