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Study register · detail Narrative Review · Epilepsy · 2019

Epidiolex as adjunct therapy for treatment of refractory epilepsy: a comprehensive review with a focus on adverse effects

Sekar et al. ·F1000Research Impact 1.0
Unclear 109 citations
SampleNarrative Review
Durationunclear
ControlPlacebo
Endpointseizure frequency
Blindingn.a.
DesignNarrative Review
Cannabinoidcbd
Routeoral
Key finding

Review summarizes findings that CBD (Epidiolex) can reduce seizure frequency in treatment-resistant epilepsy, but places emphasis on side effects.

Summary

Narrative review on Epidiolex (99% pure oral CBD extract) as add-on therapy for refractory epilepsy; summarizes results of several randomized controlled and open-label trials that led to FDA approval and DEA scheduling in Schedule V (CSA). Focus on tolerability profile and side effects of CBD in treatment-refractory epilepsy.

P
PopulationChildren and adolescents with treatment-refractory epilepsy (Dravet syndrome n=120, Lennox-Gastaut syndrome n=225), age 2–18 or 2–55 years
I
InterventionEpidiolex (99% pure oral CBD), 10 or 20 mg/kg/day, 14 weeks treatment duration
C
ControlPlacebo
O
OutcomeDravet: median reduction in convulsive seizures 38,9% vs. 13,3% placebo (p=0,01); Lennox-Gastaut: significant reduction in total seizure frequency 28,6% vs. 9% (p=0,03); 62% CGIC improvement vs. 34% placebo (p=0,02)
Quality profile
Sample size —
Blinding —
Effect size —
Citations / year ★★★★★
Authors
Sekar K, Pack A
DOI 10.12688/f1000research.16515.1↗
Design: Narrative Review
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Abstract
Medically refractory epilepsy remains an area of intense clinical and scientific interest since a significant porportion of patients continue to suffer from debilitating seizures despite available therapies. In this setting, recent studies have focused on assessing the benefits of cannabidiol (CBD)-enriched cannabis, a plant based product without psychoactive properties which has been shown to decrease seizure frequency in animal models. More recently, several randomized controlled and open label trials have studied the effects of Epidiolex, a 99% pure oral CBD extract, on patients with refractory epilepsy. This in turn has led to the FDA approval of and more recently, to the Drug Enforcement Administration's placement of Epidiolex into schedule V of the Controlled Substances Act (CSA). In this review, we summarize the major findings of several recent large-scale studies using this product with a focus on its adverse effects.
Indication
Further studies on Epilepsy
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S Devinsky et al. · 2018 · The New England journal of medicine
973 citations
Effect of Cannabidiol on Drop Seizures in the Lennox-Gastaut Syndrome.
Clear benefit RCT

Multizentrische Phase-III-RCT bei Lennox-Gastaut-Syndrom (n=225, Alter 2-55 Jahre, 30 Zentren), Cannabidiol 20 mg/kg vs. 10 mg/kg vs. Placebo (14 Wochen). Baseline: median 85 Drop-Seizures/28 Tage. Mediane Reduktion der Drop-Seizure-Frequenz: 41,9% (20 mg/kg, p=0,005 vs. Placebo), 37,2% (10 mg/kg, p=0,002 vs. Placebo), 17,2% (Placebo). Häufigste Nebenwirkungen: Somnolenz, verminderter Appetit, Diarrhö (dosisabhängig); 6 Patienten (20 mg/kg-Gruppe) und 1 Patient (10 mg/kg-Gruppe) brachen wegen Nebenwirkungen ab.

10.1056/nejmoa1714631 View study →
S Devinsky et al. · 2017 · New England Journal of Medicine
1652 citations
Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome
Clear benefit RCT

n=120 Dravet-Syndrom (therapierefraktär), CBD 20mg/kg/d vs. Placebo über 14 Wochen; median konvulsive Anfallsreduktion 38,9% (CBD) vs. 13,3% (Placebo), adjustierte Differenz -22,8 Prozentpunkte (95%-CI -41,1 bis -5,4; p=0,01); 5% anfallsfrei (CBD) vs. 0% (Placebo).

10.1056/nejmoa1611618 View study →
S Thiele et al. · 2018 · The Lancet
881 citations
Cannabidiol in patients with seizures associated with Lennox-Gastaut syndrome (GWPCARE4): a randomised, double-blind, placebo-controlled phase 3 trial
Clear benefit RCT

Phase-III-RCT (GWPCARE4) bei Lennox-Gastaut-Syndrom, n=171 (2–55 Jahre), randomisiert zu CBD 20 mg/kg/d vs. Placebo über 14 Wochen. Primärer Endpunkt: prozentuale Reduktion der monatlichen Drop-Seizure-Frequenz. Multizentrisch (24 Zentren USA, Niederlande, Polen). 14 Patienten in CBD-Gruppe, 1 in Placebo-Gruppe brachen ab. [Numerische Outcomes im Abstract abgeschnitten; Volltext zeigt signifikante Drop-Seizure-Reduktion vs. Placebo].

10.1016/s0140-6736(18)30136-3 View study →

The impediment to action advances action. — Marcus Aurelius