{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T14:05:18Z","timestamp":1792591518981,"version":"4.5.0"},"reference-count":16,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T00:00:00Z","timestamp":1761782400000},"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":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Highly purified cannabidiol (CBD) is approved as adjunctive therapy for seizures associated with Dravet syndrome (DS), Lennox\u2013Gastaut syndrome (LGS), and tuberous sclerosis complex (TSC), although its role in other developmental and epileptic encephalopathies (DEEs) remains unexplored. The aim of this study was to assess the real\u2010world use, efficacy, and safety of CBD across a broad cohort of patients with DEEs, including off\u2010label indications.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this retrospective study, we evaluated 107 patients with DEEs treated with CBD for \u22653\u2009months between 2020 and 2024. Data on seizure frequency, tolerability, retention, and non\u2010seizure outcomes were collected. Efficacy was defined as \u226550% or \u226575% seizure reduction. Statistical analyses explored predictors of response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Patients had LGS (55.1%), DS (16.8%), TSC (8.4%), or other DEEs (19.6%), with a genetic etiology in 56.1%. At a median follow\u2010up of 20\u2009months, 69% achieved \u226550% seizure reduction, and 21% achieved \u226575% reduction. Patients with LGS, TSC, and other DEEs showed higher efficacy and retention rates compared to DS. Genetic or unknown etiology was associated with better outcomes (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.011). Combination with valproate was associated with reduced efficacy (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.006), while combination with clobazam had no significant effect on efficacy nor safety. Non\u2010seizure improvements included increased alertness (56%), improved sleep quality (25%), and enhanced motor performance (14%). Adverse events occurred in 33.6%, mostly mild and transient; 9% discontinued due to side effects.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significances<\/jats:title>\n                    <jats:p>This study confirms the effectiveness and good tolerability of CBD in a real\u2010world DEE population, including off\u2010label use. These findings support expanding CBD indications and underscore the need for prospective studies targeting both seizure and developmental outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Plain language summary<\/jats:title>\n                    <jats:p>This study looked at the use of cannabidiol (CBD), a cannabis\u2010based medicine, in 107 people with severe forms of epilepsy called developmental and epileptic encephalopathies (DEEs). With CBD add\u2010on, about two\u2010thirds of patients had fewer seizures, and some caregivers noticed improvements in alertness, sleep, or movement. Most patients tolerated the treatment well, but some experienced side effects, and a few had to stop taking it. While the results are promising, more research is needed to confirm how effective and safe CBD is for different types of DEEs, especially those not currently approved for treatment with CBD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epi4.70149","type":"journal-article","created":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T10:14:05Z","timestamp":1761819245000},"page":"1806-1813","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Real\u2010world efficacy and safety of cannabidiol in developmental and epileptic encephalopathies"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3311-2765","authenticated-orcid":false,"given":"Marco","family":"Perulli","sequence":"first","affiliation":[{"name":"Fondazione Policlinico Universitario A.\u00a0Gemelli IRCCS  Rome Italy"},{"name":"Universit\u00e0 Cattolica del Sacro Cuore  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maddalena","family":"Bianchetti","sequence":"additional","affiliation":[{"name":"Fondazione Policlinico Universitario A.\u00a0Gemelli IRCCS  Rome Italy"},{"name":"Universit\u00e0 Cattolica del Sacro Cuore  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloria","family":"Pantalone","sequence":"additional","affiliation":[{"name":"Child Neurology and Psychiatric Unit Pediatric Hospital G. Salesi, Azienda Ospedaliero\u2010Universitaria Delle Marche  Ancona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8278-6953","authenticated-orcid":false,"given":"Michela","family":"Quintiliani","sequence":"additional","affiliation":[{"name":"Fondazione Policlinico Universitario A.\u00a0Gemelli IRCCS  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4132-6221","authenticated-orcid":false,"given":"Maria Luigia","family":"Gambardella","sequence":"additional","affiliation":[{"name":"Fondazione Policlinico Universitario A.\u00a0Gemelli IRCCS  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-2300-1514","authenticated-orcid":false,"given":"Maria","family":"Picilli","sequence":"additional","affiliation":[{"name":"Fondazione Policlinico Universitario A.\u00a0Gemelli IRCCS  Rome Italy"},{"name":"Universit\u00e0 Cattolica del Sacro Cuore  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9212-2691","authenticated-orcid":false,"given":"Carla","family":"Marini","sequence":"additional","affiliation":[{"name":"Child Neurology and Psychiatric Unit Pediatric Hospital G. Salesi, Azienda Ospedaliero\u2010Universitaria Delle Marche  Ancona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7177-4500","authenticated-orcid":false,"given":"Elisabetta","family":"Cesaroni","sequence":"additional","affiliation":[{"name":"Child Neurology and Psychiatric Unit Pediatric Hospital G. Salesi, Azienda Ospedaliero\u2010Universitaria Delle Marche  Ancona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0491-4021","authenticated-orcid":false,"given":"Domenica Immacolata","family":"Battaglia","sequence":"additional","affiliation":[{"name":"Fondazione Policlinico Universitario A.\u00a0Gemelli IRCCS  Rome Italy"},{"name":"Universit\u00e0 Cattolica del Sacro Cuore  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,30]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMOA1714631"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1611618"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/JAMANEUROL.2020.4607"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/EPI4.70078"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2018.05.013"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/epi4.12740"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2023.07.009"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.12631"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2023"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1080\/14656566.2024.2373350"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.18378"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/S11910\u2010018\u20100882\u2010Y"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/CPT.3004"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1177\/17562864231207755"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.881617"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.SEIZURE.2025.04.017"}],"container-title":["Epilepsia Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/epi4.70149","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T16:27:22Z","timestamp":1766161642000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/epi4.70149"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,30]]},"references-count":16,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1002\/epi4.70149"],"URL":"https:\/\/doi.org\/10.1002\/epi4.70149","archive":["Portico"],"relation":{},"ISSN":["2470-9239","2470-9239"],"issn-type":[{"value":"2470-9239","type":"print"},{"value":"2470-9239","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,30]]},"assertion":[{"value":"2025-05-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-30","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}