PMID- 33181893 OWN - NLM STAT- MEDLINE DCOM- 20210414 LR - 20210414 IS - 1525-5069 (Electronic) IS - 1525-5050 (Linking) VI - 112 DP - 2020 Nov TI - Long-term efficacy and safety of cannabidiol (CBD) in children with treatment-resistant epilepsy: Results from a state-based expanded access program. PG - 107474 LID - S1525-5050(20)30654-5 [pii] LID - 10.1016/j.yebeh.2020.107474 [doi] AB - INTRODUCTION: An intermediate-sized, multicenter, expanded-access study was opened in 2015 through the support of the State of Georgia. This study provided children with treatment-resistant epilepsy (TRE) access to plant-derived highly purified cannabidiol (CBD; Epidiolex(R) in the US; Epidyolex(R) in the EU; 100 mg/mL oral solution). These children had failed to achieve seizure freedom with available treatment options and were ineligible to participate in randomized controlled trials that only included patients with Lennox-Gastaut and Dravet syndromes. METHODS: Cannabidiol safety, changes in seizure type, frequency, and seizure-free days were evaluated for children aged 1-18 years (at time of consent) as an adjunctive treatment for 36 months. The study consisted of a two-month baseline period, a titration period, treatment period, and optional titration period, which occurred after >/=26 weeks of treatment. Cannabidiol treatment was administered up to a targeted dose of 25 mg/kg/day, with an optional secondary treatment up to 50 mg/kg/day. Daily seizure type, seizure frequency, and seizure-free days were recorded in a Web-based diary, and changes in these outcomes were recorded and analyzed for the duration of the study. The occurrence of adverse events (AEs) was also recorded. RESULTS: The median percentage change in seizures for 45 patients in Months 3, 6, 12, 18, 24, and 36 showed a statistically significant (p < 0.001) reduction in major seizures (ranging from 54 to 72% at various time points) and all seizures (61-70%) compared with baseline. A mean increase in seizure-free days per 28 days was >5 in all treatment periods after Month 2, and an average increase of 7.52 (p < 0.001) seizure-free days per 28 days was observed at the end of follow-up compared with baseline. All patients experienced >/=1 AE. Children who transitioned to the optional secondary treatment (high-dose group) reported more AEs before increasing their dose to >25.0 mg/kg/day compared with the low-dose group. However, the average rate of AEs was significantly lower after moving to a high-dose regimen (p = 0.004). Twelve children reported 20 serious AEs, none of which were considered related to CBD. CONCLUSIONS: This study supports CBD as an adjunctive treatment for children with TRE. Treatment was well tolerated in doses up to 50 mg/kg/day. Patients who did not achieve desired results at a dose of 25.0 mg/kg/day. Decreases in major seizure frequency and an increase in seizure-free days compared with baseline were reported during treatment. This supports the efficacy and tolerability of CBD for mixed seizure etiologies. CI - Copyright (c) 2020. Published by Elsevier Inc. FAU - Park, Yong D AU - Park YD AD - Augusta University, Augusta, GA, United States. Electronic address: YPARK@augusta.edu. FAU - Linder, Daniel F AU - Linder DF AD - Augusta University, Augusta, GA, United States. Electronic address: dlinder@augusta.edu. FAU - Pope, Jamie AU - Pope J AD - Augusta University, Augusta, GA, United States. Electronic address: jampope@umd.edu. FAU - Flamini, J Robert AU - Flamini JR AD - Panda Neurology, Atlanta, GA, United States. Electronic address: rflamini@comcast.net. FAU - Moretz, Katherine AU - Moretz K AD - Memorial Health University Medical Center, Savannah, GA, United States. FAU - Diamond, Michael P AU - Diamond MP AD - Augusta University, Augusta, GA, United States. Electronic address: midiamond@augusta.edu. FAU - Long, Sarah A AU - Long SA AD - Augusta University, Augusta, GA, United States. Electronic address: salong@augusta.edu. LA - eng PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20200928 PL - United States TA - Epilepsy Behav JT - Epilepsy & behavior : E&B JID - 100892858 RN - 0 (Anticonvulsants) RN - 19GBJ60SN5 (Cannabidiol) SB - IM MH - Adolescent MH - Anticonvulsants/therapeutic use MH - *Cannabidiol/therapeutic use MH - Child MH - Child, Preschool MH - *Epilepsies, Myoclonic/drug therapy MH - *Epilepsy/drug therapy MH - Humans MH - Infant MH - Seizures/drug therapy OTO - NOTNLM OT - Cannabidiol OT - Pediatric epilepsy OT - Treatment-resistant epilepsy COIS- Declaration of competing interest Yong Park, MD served as a speaker and consultant for Greenwich Biosciences, Inc. All other authors have no conflicts of interest relevant to this article to disclose. EDAT- 2020/11/14 06:00 MHDA- 2021/04/15 06:00 CRDT- 2020/11/13 01:00 PHST- 2020/07/13 00:00 [received] PHST- 2020/09/02 00:00 [revised] PHST- 2020/09/06 00:00 [accepted] PHST- 2020/11/13 01:00 [entrez] PHST- 2020/11/14 06:00 [pubmed] PHST- 2021/04/15 06:00 [medline] AID - S1525-5050(20)30654-5 [pii] AID - 10.1016/j.yebeh.2020.107474 [doi] PST - ppublish SO - Epilepsy Behav. 2020 Nov;112:107474. doi: 10.1016/j.yebeh.2020.107474. Epub 2020 Sep 28.