Adjunctive Transdermal Cannabidiol for Adults With Focal Epilepsy: A Randomized Clinical Trial.

Autor:	O'Brien TJ; Department of Neuroscience, The Central Clinical School, Monash University and The Alfred Centre, Melbourne, Victoria, Australia.; Department of Neurology, The Central Clinical School, Monash University and The Alfred Centre, Melbourne, Victoria, Australia.; Department of Medicine, The University of Melbourne, Royal Melbourne Hospital, Parkville, Victoria, Australia.; Department of Neurology, The University of Melbourne, Royal Melbourne Hospital, Parkville, Victoria, Australia., Berkovic SF; Epilepsy Research Centre, University of Melbourne, Heidelberg, Victoria, Australia., French JA; Department of Neurology, New York University Grossman School of Medicine, New York., Messenheimer JA; John Messenheimer PLLC, Moncure, North Carolina., Sebree TB; Zynerba Pharmaceuticals, Devon, Pennsylvania., Bonn-Miller MO; Zynerba Pharmaceuticals, Devon, Pennsylvania., Gutterman DL; Zynerba Pharmaceuticals, Devon, Pennsylvania.
Jazyk:	angličtina
Zdroj:	JAMA network open [JAMA Netw Open] 2022 Jul 01; Vol. 5 (7), pp. e2220189. Date of Electronic Publication: 2022 Jul 01.
DOI:	10.1001/jamanetworkopen.2022.20189
Abstrakt:	Importance: Cannabidiol has shown efficacy in randomized clinical trials for drug-resistant epilepsy in specific syndromes that predominantly affect children. However, high-level evidence for the efficacy and safety of cannabidiol in the most common form of drug-resistant epilepsy in adults, focal epilepsy, is lacking. Objective: To investigate the efficacy, safety, and tolerability of transdermally administered cannabidiol in adults with drug-resistant focal epilepsy. Design, Setting, and Participants: A randomized, double-blind, placebo-controlled, multicenter clinical trial at 14 epilepsy trial centers in Australia and New Zealand. Participants were adults with drug-resistant focal epilepsy receiving a stable regimen of up to 3 antiseizure medications. Data were analyzed from July 2017 to November 2018. Interventions: Eligible participants were randomized (1:1:1) to 195-mg or 390-mg transdermal cannabidiol or placebo twice daily for 12 weeks, after which they could enroll in an open-label extension study for up to 2 years. Main Outcomes and Measures: Seizure frequency was self-reported using a daily diary. The primary efficacy end point was the least squares mean difference in the log-transformed total seizure frequency per 28-day period, adjusted to a common baseline log seizure rate, during the 12-week treatment period. Results: A total of 188 patients (45% male [85 patients] and 54.8% female [103 patients]) with a mean (SD) age of 39.2 (12.78) years were randomized, treated, and analyzed (195-mg cannabidiol, 63 participants; 390-mg cannabidiol, 62 participants; placebo, 63 participants). At week 12 of the double-blind period, there was no difference in seizure frequency between placebo (mean [SD] 2.49 [1.31] seizures per 28 days) and 195-mg cannabidiol (mean [SD] 2.51 [1.15] seizures per 28 days; least squares mean difference, 0.014; 95% CI, -0.175 to 0.203; P = .89) or 390-mg cannabidiol (mean [SD] 2.59 [1.12] seizures per 28 days; least squares mean difference, 0.096; 95% CI, -0.093 to 0.285; P = .32). By month 6 of the open-label extension, 115 patients (60.8%) achieved a seizure reduction of at least 50%. Treatment-emergent adverse events occurred in 50.4% (63 of 125 participants) of the cannabidiol group vs 41.3% (26 of 63 participants) in the placebo group, with a treatment difference of 9.1% (95% CI, -6.0% to 23.6%), and occurred at similar rates in the cannabidiol groups. Few participants discontinued (7% [14 of 188 participants]), and most (98% [171 of 174 participants]) continued into the open-label extension. Conclusions and Relevance: Both doses of transdermal cannabidiol were well tolerated and safe. No significant difference in efficacy was observed between cannabidiol and placebo during the double-blind treatment period. The open-label extension demonstrated the long-term safety, tolerability, and acceptability of transdermal cannabidiol delivery. Trial Registration: ACTRN12616000510448 (double-blind); ACTRN12616001455459 (open-label).
Databáze:	MEDLINE
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