{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T12:42:43Z","timestamp":1792154563450,"version":"4.4.0"},"reference-count":42,"publisher":"Springer Science and Business Media LLC","issue":"17","license":[{"start":{"date-parts":[[2018,11,1]],"date-time":"2018-11-01T00:00:00Z","timestamp":1541030400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Drugs"],"published-print":{"date-parts":[[2018,11]]},"DOI":"10.1007\/s40265-018-0992-5","type":"journal-article","created":{"date-parts":[[2018,11,2]],"date-time":"2018-11-02T20:59:52Z","timestamp":1541192392000},"page":"1791-1804","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":191,"title":["Efficacy and Safety of Cannabidiol in Epilepsy: A Systematic Review and Meta-Analysis"],"prefix":"10.1007","volume":"78","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8748-0083","authenticated-orcid":false,"given":"Simona","family":"Lattanzi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Brigo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugen","family":"Trinka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaetano","family":"Zaccara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Cagnetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cinzia","family":"Del Giovane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro","family":"Silvestrini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,11,3]]},"reference":[{"key":"992_CR1","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1212\/01.wnl.0000252807.38124.a3","volume":"68","author":"D Hirtz","year":"2007","unstructured":"Hirtz D, Thurman DJ, Gwinn-Hardy K, Mohamed M, Chaudhuri AR, Zalutsky R. How common are the \u201ccommon\u201d neurologic disorders? Neurology. 2007;68:326\u201337.","journal-title":"Neurology."},{"key":"992_CR2","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1212\/WNL.0000000000000619","volume":"83","author":"C Cagnetti","year":"2014","unstructured":"Cagnetti C, Lattanzi S, Foschi N, Provinciali L, Silvestrini M. Seizure course during pregnancy in catamenial epilepsy. Neurology. 2014;83:339\u201344.","journal-title":"Neurology."},{"key":"992_CR3","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1016\/S0140-6736(95)91208-8","volume":"346","author":"OC Cockerell","year":"1995","unstructured":"Cockerell OC, Johnson AL, Sander JW, Hart YM, Shorvon SD. Remission of epilepsy: results from the national general practice study of epilepsy. Lancet. 1995;346:140\u20134.","journal-title":"Lancet"},{"key":"992_CR4","doi-asserted-by":"publisher","unstructured":"Lattanzi S, Zaccara G, Giovannelli F, Grillo E, Nardone R, Silvestrini M, et al. Antiepileptic mono-therapy in newly diagnosed focal epilepsy. A network meta-analysis. Acta Neurol Scand. https:\/\/doi.org\/10.1111\/ane.13025 (Epub 2018 Sep 8).","DOI":"10.1111\/ane.13025"},{"key":"992_CR5","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/j.seizure.2015.03.003","volume":"27","author":"S Lattanzi","year":"2015","unstructured":"Lattanzi S, Cagnetti C, Foschi N, Provinciali L, Silvestrini M. Lacosamide monotherapy for partial onset seizures. Seizure. 2015;27:71\u20134.","journal-title":"Seizure."},{"key":"992_CR6","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1056\/NEJM200002033420503","volume":"342","author":"P Kwan","year":"2000","unstructured":"Kwan P, Brodie MJ. Early identification of refractory epilepsy. N Engl J Med. 2000;342:314\u20139.","journal-title":"N Engl J Med"},{"key":"992_CR7","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1111\/ane.12803","volume":"137","author":"S Lattanzi","year":"2018","unstructured":"Lattanzi S, Cagnetti C, Foschi N, Lorusso A, Provinciali L, Silvestrini M. Eslicarbazepine acetate as adjunctive treatment in partial-onset epilepsy. Acta Neurol Scand. 2018;137:29\u201332.","journal-title":"Acta Neurol Scand"},{"key":"992_CR8","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1016\/j.braindev.2017.12.012","volume":"40","author":"S Lattanzi","year":"2018","unstructured":"Lattanzi S, Cagnetti C, Matricardi S, Silvestrini M. Palliative non-resective surgery for drug-resistant epilepsy. Brain Dev. 2018;40:512\u20133.","journal-title":"Brain Dev."},{"key":"992_CR9","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1111\/epi.12631","volume":"55","author":"O Devinsky","year":"2014","unstructured":"Devinsky O, Cilio MR, Cross H, Fernandez-Ruiz J, French J, Hill C, et al. Cannabidiol: pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders. Epilepsia. 2014;55:791\u2013802.","journal-title":"Epilepsia."},{"key":"992_CR10","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1007\/s13311-015-0377-3","volume":"12","author":"C Ibeas Bih","year":"2015","unstructured":"Ibeas Bih C, Chen T, Nunn AV, Bazelot M, Dallas M, Whalley BJ. Molecular targets of cannabidiol in neurological disorders. Neurotherapeutics. 2015;12:699\u2013730.","journal-title":"Neurotherapeutics."},{"key":"992_CR11","unstructured":"GW Pharmaceuticals plc and its U.S. subsidiary Greenwich Biosciences announce FDA approval of EPIDIOLEX\u00ae (cannabidiol) oral solution\u2014the first plant-derived cannabinoid prescription medicine. https:\/\/www.gwpharm.com\/about-us\/news\/gw-pharmaceuticals-plc-and-its-us-subsidiary-greenwich-biosciences-announce-fda . Accessed Sep 2018."},{"key":"992_CR12","doi-asserted-by":"crossref","unstructured":"Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6:e1000097.","DOI":"10.1371\/journal.pmed.1000097"},{"key":"992_CR13","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1016\/S1474-4422(15)00379-8","volume":"15","author":"O Devinsky","year":"2016","unstructured":"Devinsky O, Marsh E, Friedman D, Thiele E, Laux L, Sullivan J, et al. Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trial. Lancet Neurol. 2016;15:270\u20138.","journal-title":"Lancet Neurol."},{"key":"992_CR14","unstructured":"Cochrane handbook for systematic reviews of interventions. Version 5.1.0 [updated March 2011]. Higgins JPT, Green S, editors. The Cochrane Collaboration, 2011. http:\/\/handbook-5-1.cochrane.org\/ . Accessed Jun 2018."},{"key":"992_CR15","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1136\/bmj.327.7414.557","volume":"327","author":"JP Higgins","year":"2003","unstructured":"Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557\u201360.","journal-title":"BMJ"},{"key":"992_CR16","doi-asserted-by":"publisher","first-page":"1539","DOI":"10.1002\/sim.1186","volume":"21","author":"JP Higgins","year":"2002","unstructured":"Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21:1539\u201358.","journal-title":"Stat Med"},{"key":"992_CR17","doi-asserted-by":"publisher","first-page":"1344","DOI":"10.1212\/WNL.0000000000002545","volume":"86","author":"S Lattanzi","year":"2016","unstructured":"Lattanzi S, Cagnetti C, Foschi N, Provinciali L, Silvestrini M. Brivaracetam add-on for refractory focal epilepsy: a systematic review and meta-analysis. Neurology. 2016;86:1344\u201352.","journal-title":"Neurology."},{"key":"992_CR18","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1007\/s40263-018-0504-x","volume":"32","author":"S Lattanzi","year":"2018","unstructured":"Lattanzi S, Brigo F, Grillo E, Cagnetti C, Verrotti A, Zaccara G, et al. Adjunctive eslicarbazepine acetate in pediatric patients with focal epilepsy: a systematic review and meta-analysis. CNS Drugs. 2018;32:189\u201396.","journal-title":"CNS Drugs"},{"key":"992_CR19","doi-asserted-by":"crossref","unstructured":"Lattanzi S, Grillo E, Brigo F, Silvestrini M. Efficacy and safety of perampanel in Parkinson\u2019s disease. A systematic review with meta-analysis. J Neurol. 2018;265:733\u201340.","DOI":"10.1007\/s00415-017-8681-y"},{"key":"992_CR20","doi-asserted-by":"publisher","first-page":"1697","DOI":"10.1007\/s00415-017-8505-0","volume":"264","author":"S Lattanzi","year":"2017","unstructured":"Lattanzi S, Cagnetti C, Danni M, Provinciali L, Silvestrini M. Oral and intravenous steroids for multiple sclerosis relapse: a systematic review and meta-analysis. J Neurol. 2017;264:1697\u2013704.","journal-title":"J Neurol"},{"key":"992_CR21","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1159\/000488401","volume":"45","author":"S Lattanzi","year":"2018","unstructured":"Lattanzi S, Brigo F, Cagnetti C, Di Napoli M, Silvestrini M. Patent foramen ovale and cryptogenic stroke or transient ischemic attack: to close or not to close? A systematic review and meta-analysis. Cerebrovasc Dis. 2018;45:193\u2013203.","journal-title":"Cerebrovasc Dis."},{"key":"992_CR22","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1016\/j.jns.2018.05.024","volume":"391","author":"S Lattanzi","year":"2018","unstructured":"Lattanzi S, Brigo F, Di Napoli M, Cagnetti C, Corradetti T, Silvestrini M. Endovascular treatment of symptomatic vertebral artery stenosis: a systematic review and meta-analysis. J Neurol Sci. 2018;391:48\u201353.","journal-title":"J Neurol Sci"},{"key":"992_CR23","doi-asserted-by":"crossref","unstructured":"Devinsky O, Patel AD, Thiele EA, Wong MH, Appleton R, Harden CL, et al.; GWPCARE1 Part A Study Group. Randomized, dose-ranging safety trial of cannabidiol in Dravet syndrome. Neurology. 2018;90:e1204\u201311.","DOI":"10.1212\/WNL.0000000000005254"},{"key":"992_CR24","doi-asserted-by":"crossref","unstructured":"Devinsky O, Cross JH, Laux L, Marsh E, Miller I, Nabbout R, et al.; Cannabidiol in Dravet Syndrome Study Group. Trial of cannabidiol for drug-resistant seizures in the Dravet syndrome. N Engl J Med. 2017;376:2011\u20132020.","DOI":"10.1056\/NEJMoa1611618"},{"key":"992_CR25","doi-asserted-by":"crossref","unstructured":"Devinsky O, Patel AD, Cross JH, Villanueva V, Wirrell EC, Privitera M, et al.; GWPCARE3 Study Group. Effect of cannabidiol on drop seizures in the Lennox\u2013Gastaut syndrome. N Engl J Med. 2018;378:1888-1897.","DOI":"10.1056\/NEJMoa1714631"},{"key":"992_CR26","doi-asserted-by":"crossref","unstructured":"Thiele EA, Marsh ED, French JA, Mazurkiewicz-Beldzinska M, Benbadis SR, Joshi C, et al.; GWPCARE4 Study Group. Cannabidiol in patients with seizures associated with Lennox\u2013Gastaut syndrome (GWPCARE4): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2018;391:1085\u201396.","DOI":"10.1016\/S0140-6736(18)30136-3"},{"key":"992_CR27","doi-asserted-by":"publisher","unstructured":"Lattanzi S, Brigo F, Cagnetti C, Trinka E, Silvestrini M. Efficacy and safety of adjunctive cannabidiol in patients with Lennox\u2013Gastaut syndrome: a systematic review and meta-analysis. CNS Drugs. https:\/\/doi.org\/10.1007\/s40263-018-0558-9 (Epub 2018 Aug 21).","DOI":"10.1007\/s40263-018-0558-9"},{"key":"992_CR28","doi-asserted-by":"crossref","unstructured":"Morrison G, Sardu M, Rasmussen C, Sommerville K, Roberts C, Blakey GE. Exposure-response analysis of cannabidiol oral solution for the treatment of Lennox\u2013Gastaut syndrome [abstract no. 2.281]. The American Epilepsy Society Annual Meeting; 1\u20135 Dec 2017; Washington, DC. https:\/\/www.aesnet.org\/meetings_events\/annual_meeting_abstracts\/view\/344717 . Accessed Jul 2018.","DOI":"10.1212\/WNL.90.15_supplement.P1.271"},{"key":"992_CR29","unstructured":"FDA. Cannabidiol oral solution. Full prescribing information. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2018\/210365lbl.pdf . Accessed Jul 2018."},{"key":"992_CR30","doi-asserted-by":"crossref","unstructured":"Ng YT, Conry JA, Drummond R, Stolle J, Weinberg MA; OV-1012 Study Investigators. Randomized, phase III study results of clobazam in Lennox\u2013Gastaut syndrome. Neurology. 2011;77:1473\u201381.","DOI":"10.1212\/WNL.0b013e318232de76"},{"key":"992_CR31","doi-asserted-by":"publisher","first-page":"1950","DOI":"10.1212\/01.wnl.0000303813.95800.0d","volume":"70","author":"T Glauser","year":"2008","unstructured":"Glauser T, Kluger G, Sachdeo R, Krauss G, Perdomo C, Arroyo S. Rufinamide for generalized seizures associated with Lennox\u2013Gastaut syndrome. Neurology. 2008;70:1950\u20138.","journal-title":"Neurology."},{"key":"992_CR32","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1177\/08830738060210062101","volume":"21","author":"C Chiron","year":"2006","unstructured":"Chiron C, Tonnelier S, Rey E, Brunet ML, Tran A, d\u2019Athis P, et al. Stiripentol in childhood partial epilepsy: randomized placebo-controlled trial with enrichment and withdrawal design. J Child Neurol. 2006;21:496\u2013502.","journal-title":"J Child Neurol"},{"key":"992_CR33","unstructured":"FDA briefing document. Peripheral and central nervous system drugs. Advisory Committee Meeting. April 19, 2018. NDA 210365. Cannabidiol. https:\/\/www.fda.gov\/downloads\/advisorycommittees\/committeesmeetingmaterials\/drugs\/peripheralandcentralnervoussystemdrugsadvisorycommittee\/ucm604736.pdf . Accessed Jul 2018."},{"key":"992_CR34","unstructured":"US Department of Health and Human Services. Guidance for industry. Drug-induced liver injury: premarketing clinical evaluation. 2009. https:\/\/www.fda.gov\/downloads\/Guidances\/UCM174090.pdf . Accessed Jul 2018."},{"key":"992_CR35","doi-asserted-by":"publisher","first-page":"1246","DOI":"10.1111\/epi.13060","volume":"56","author":"AL Geffrey","year":"2015","unstructured":"Geffrey AL, Pollack SF, Bruno PL, Thiele EA. Drug-drug interaction between clobazam and cannabidiol in children with refractory epilepsy. Epilepsia. 2015;56:1246\u201351.","journal-title":"Epilepsia."},{"key":"992_CR36","unstructured":"Thiele EA, Devinsky O, Checketts D, Knappertz V. Cannabidiol (CBD) treatment responders analysis in patients with Lennox\u2013Gastaut syndrome (LGS) on and off clobazam (CLB) [abstract no. 1.436]. The American Epilepsy Society Annual Meeting; 1\u20135 Dec 2017; Washington, DC. https:\/\/www.aesnet.org\/meetings_events\/annual_meeting_abstracts\/view\/381224 . Accessed Jul 2018."},{"key":"992_CR37","doi-asserted-by":"crossref","unstructured":"Gloss D, Vickrey B. Cannabinoids for epilepsy. Cochrane Database Syst Rev. 2014;(3):CD009270.","DOI":"10.1002\/14651858.CD009270.pub3"},{"key":"992_CR38","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1136\/jnnp-2017-317168","volume":"89","author":"E Stockings","year":"2018","unstructured":"Stockings E, Zagic D, Campbell G, Weier M, Hall WD, Nielsen S, et al. Evidence for cannabis and cannabinoids for epilepsy: a systematic review of con-trolled and observational evidence. J Neurol Neurosurg Psychiatry. 2018;89:741\u201353.","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"992_CR39","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.jclinepi.2017.11.025","volume":"95","author":"KM Rhodes","year":"2018","unstructured":"Rhodes KM, Turner RM, Savovi\u0107 J, Jones HE, Mawdsley D, Higgins JPT. Between-trial heterogeneity in meta-analyses may be partially explained by reported design characteristics. J Clin Epidemiol. 2018;95:45\u201354.","journal-title":"J Clin Epidemiol"},{"key":"992_CR40","doi-asserted-by":"crossref","unstructured":"Devinsky O, Nabbout R, Miller I, Laux L, Zolnowska M, Wright S, et al. Maintenance of long-term safety and efficacy of cannabidiol (CBD) treatment in Dravet syndrome (DS): results of the open-label extension (OLE) trial (GWPCARE5) [abstract no. 1.289]. The American Epilepsy Society Annual Meeting; 1\u20135 Dec 2017; Washington, DC. https:\/\/www.aesnet.org\/meetings_events\/annual_meeting_abstracts\/view\/343046 . Accessed Jul 2018.","DOI":"10.1055\/s-0038-1676029"},{"key":"992_CR41","unstructured":"Marsh ED, Mazurkiewicz-Beldzinska M, Halford JJ, Gunning B, Checketts D, Nichol K, et al. Maintained safety and efficacy of cannabidiol (CBD) in a long-term open-label trial in patients with Lennox\u2013Gastaut syndrome (LGS) (GWPCARE 5) [abstract no. 2.271]. The American Epilepsy Society Annual Meeting; 1\u20135 Dec 2017; Washington, DC. https:\/\/www.aesnet.org\/meetings_events\/annual_meeting_abstracts\/view\/344387 . Accessed Jul 2018."},{"key":"992_CR42","doi-asserted-by":"publisher","unstructured":"Szaflarski JP, Bebin EM, Comi AM, Patel AD, Joshi C, Checketts D, et al.; CBD EAP study group. Long-term safety and treatment effects of cannabidiol in children and adults with treatment-resistant epilepsies: expanded access program results. Epilepsia. 2018;59(8):1540\u20138. https:\/\/doi.org\/10.1111\/epi.14477 .","DOI":"10.1111\/epi.14477"}],"container-title":["Drugs"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s40265-018-0992-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s40265-018-0992-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s40265-018-0992-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,11]],"date-time":"2024-07-11T21:01:25Z","timestamp":1720731685000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s40265-018-0992-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,11]]},"references-count":42,"journal-issue":{"issue":"17","published-print":{"date-parts":[[2018,11]]}},"alternative-id":["992"],"URL":"https:\/\/doi.org\/10.1007\/s40265-018-0992-5","relation":{},"ISSN":["0012-6667","1179-1950"],"issn-type":[{"value":"0012-6667","type":"print"},{"value":"1179-1950","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,11]]},"assertion":[{"value":"3 November 2018","order":1,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with Ethical Standards"}},{"value":"No funding has been received for the conduct of this study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Funding"}},{"value":"Simona Lattanzi, Claudia Cagnetti, Cinzia Del Giovane and Mauro Silvestrini have no conflicts of interest directly relevant to the content of this study. Francesco Brigo acted as a consultant for Eisai. Eugen Trinka received speaker\u2019s honoraria from UCB, Biogen, Gerot-Lannach, Bial, Eisai, Takeda, Newbridge, Sunovion Pharmaceuticals Inc., LivaNova, and Novartis; consultancy funds from UCB, Biogen, Gerot-Lannach, Bial, Eisai, Takeda, Newbridge, GW Pharmaceuticals, Sunovion Pharmaceuticals Inc., and Novartis; and directorship funds from Neuroconsult GmbH. Eugen Trinka\u2019s institution received grants from Biogen, Red Bull, Merck, UCB, the European Union, FWF \u00d6sterreichischer Fond zur Wissenschaftsf\u00f6rderung, and Bundesministerium f\u00fcr Wissenschaft und Forschung. Gaetano Zaccara received speaker\u2019s or consultancy fees from Eisai, Sanofi-Aventis, and UCB Pharma.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}