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Meta-Analysis
. 2021 Feb;143(2):154-163.
doi: 10.1111/ane.13351. Epub 2020 Oct 22.

Cannabidiol in conjunction with clobazam: analysis of four randomized controlled trials

Boudewijn Gunning  1 , Maria Mazurkiewicz-Bełdzińska  2 , Richard F M Chin  3 , Hari Bhathal  4 , Charlotte Nortvedt  5 , Eduardo Dunayevich  6 , Daniel Checketts  5
Affiliations
Meta-Analysis

Cannabidiol in conjunction with clobazam: analysis of four randomized controlled trials

Boudewijn Gunning et al. Acta Neurol Scand. 2021 Feb.

Abstract

Objectives: To assess the efficacy and safety profile of add-on cannabidiol (CBD) in patients with Lennox-Gastaut syndrome (LGS) and Dravet syndrome (DS) on clobazam and in the overall population of four randomized, controlled phase 3 trials.

Methods: Patients received plant-derived, highly purified CBD medicine (Epidiolex® in the USA; Epidyolex® in Europe; 100 mg/ml oral solution) at a dose of 10 or 20 mg/kg/day, or placebo for 14 weeks. A subgroup analysis of patients on clobazam and meta-analysis by syndrome were conducted. The primary endpoint was percentage reduction in primary seizure type during the treatment period.

Results: 396 patients with LGS (49% on clobazam) and 318 patients with DS (64% on clobazam) were included. CBD treatment resulted in a reduction in primary seizure frequency vs placebo in the overall population (treatment ratio [95% confidence interval]: LGS, 0.70 [0.62-0.80]; DS, 0.71 [0.60-0.83]) and in patients receiving clobazam (LGS, 0.56 [0.47-0.67]; DS, 0.63 [0.52-0.77]). The antiseizure efficacy of CBD was also demonstrated across other endpoints vs placebo (≥50% responder rate, total seizure frequency, number of seizure-free days, and Subject/Caregiver Global Impression of Change scores) in the overall populations and in patients receiving clobazam. There were higher incidences of somnolence and sedation in patients on CBD and clobazam. Most incidences of elevated transaminases occurred in patients on concomitant valproate and, to a lesser extent, clobazam.

Conclusions: Add-on CBD was effective in reducing seizures in the overall populations and in conjunction with clobazam. Somnolence and sedation occurred more frequently in patients on CBD and clobazam.

Keywords: cannabidiol; clobazam; epilepsies; epilepsy; lennox-gastaut syndrome; myoclonic; seizures.

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Conflict of interest statement

B. Gunning has received consultancy fees from GW Pharmaceuticals companies, Ovid/Takeda, and Zogenix, and has been a principal investigator for GW Research Ltd and Zogenix; M. Mazurkiewicz‐Bełdzińska has been a principal investigator for Biogen, GW Research Ltd, Ovid/Takeda, and Roche; R.F.M. Chin has received consultancy fees from Eisai, GW Pharmaceuticals companies, and Zogenix, and has been a principal investigator for GW Research Ltd; H. Bhathal has received consultancy fees from BIAL and GW Pharmaceuticals, and has been a principal investigator for Eisai and GW Research; C. Nortvedt is employed by GW Pharmaceuticals Ltd and owns shares in GW Pharmaceuticals plc; E. Dunayevich is employed by Greenwich Biosciences Inc. and owns shares in GW Pharmaceuticals plc; and D. Checketts is employed by GW Research Ltd and owns shares in GW Pharmaceuticals plc.

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