Objective: To evaluate the efficacy of open-label, highly purified cannabidiol (CBD, Epidiolex®) in treating refractory epilepsy relative to the concomitant use of clobazam (CLB) as well as the clinical implications of changes in CLB and norclobazam (nCLB) levels.
Methods: Data were examined retrospectively, in patients who either used CBD with concomitant CLB or without concomitant CLB after two months of treatment with CBD and at the point of best seizure control within the first year of treatment with CBD. Responder rates (percentage of subjects with a 50 % or greater reduction in weekly seizures from their baseline) and mean reduction in weekly seizure frequency were calculated and compared between those who concomitantly used CLB and those who did not. The relationship between the change in CLB and nCLB levels and change in mean weekly seizure frequency was also investigated within the group of subjects using concomitant CLB and CBD.
Results: We analyzed data from 47 subjects between the ages of 2.5-51 years. There was no significant difference between the concomitant CLB (n = 32) and no concomitant CLB (n = 15) groups in terms of demographics (age (p = 0.4344), race (p = 1.0000), sex (p = 0.7507)) or most epilepsy characteristics (underlying condition (all p > 0.05), mean baseline seizure frequency (p = 0.6483)). There was only one significant difference between groups regarding seizure types (more subjects with epileptic spasms in concomitant CLB group (p = 0.0413)). Concomitant AED usage was not significantly different in the two groups (all p > 0.05). Mean reduction in weekly seizure frequency was greater at the best point of seizure control within the first year than at two months of treatment with CBD, regardless of concomitant CLB usage (all p > 0.05). There was no significant difference in reduction of mean weekly seizure frequency between those who took concomitant CLB and those who did not at either time point (all p > 0.05). There was a significantly greater responder rate for subjects taking CBD and CLB than those taking CBD without CLB only at the point of best seizure control within the first year of CBD treatment (p = 0.0240). There was no strong, significant correlation between change in nCLB or CLB levels and change in seizure frequency at either time point (all |p|<0.22).
Significance: With or without concomitant CLB, CBD can be effective in reducing seizure frequency. Changes in nCLB and CLB levels do not have a clinically significant correlation with changes in weekly seizure frequency for those taking CBD with CLB.
Copyright © 2019. Published by Elsevier B.V.
Conflict of interest statement
Declaration of Competing Interest Elizabeth A. Thiele, M.D., Ph.D. has served as a paid consultant for GW Pharmaceuticals companies. The remaining authors have no conflict of interest to disclose.
Drug-drug Interaction Between Clobazam and Cannabidiol in Children With Refractory EpilepsyAL Geffrey et al. Epilepsia 56 (8), 1246-51. PMID 26114620.We report elevated CLB and nCLB levels in these subjects. The mean (± standard deviation [SD]) increase in CLB levels was 60 ± 80% (95% confidence interval (CI) [-2-91%] …
Don't Fear the Reefer-Evidence Mounts for Plant-Based Cannabidiol as Treatment for EpilepsyMS Perry. Epilepsy Curr 19 (2), 93-95. PMID 30955420.Among children and adults with the Lennox-Gastaut syndrome, the addition of cannabidiol at a dose of 10 or 20 mg/kg/d to a conventional antiepileptic regimen resulted in …
Drug-drug Interactions With Cannabidiol (CBD) Appear to Have No Effect on Treatment Response in an Open-Label Expanded Access ProgramTE Gaston et al. Epilepsy Behav 98 (Pt A), 201-206. PMID 31382177.These analyses suggest that concomitant to CBD, AEDs may not have an effect on reducing seizure frequency and severity in patients with TRE.
Cannabis for the Treatment of Epilepsy: An UpdateTE Gaston et al. Curr Neurol Neurosci Rep 18 (11), 73. PMID 30194563. - ReviewWhile the anticonvulsant mechanism of action of CBD has not been entirely elucidated, we discuss the most recent data available including its low affinity for the endocan …
Pharmacological and Therapeutic Properties of Cannabidiol for EpilepsyV Franco et al. Drugs 79 (13), 1435-1454. PMID 31372958. - ReviewCannabidiol (CBD) is a major active component of the Cannabis plant, which, unlike tetrahydrocannabinol (THC), is devoid of euphoria-inducing properties. During the last …