Adjunctive Cannabidiol in Patients with Dravet Syndrome: A Systematic Review and Meta-Analysis of Efficacy and Safety
Dravet syndrome (DS) is one of the most severe forms of drug-resistant epilepsy and available interventions fail to control seizures in most patients. Cannabidiol (CBD) is the first in a new class of antiepileptic drugs with a distinctive chemical structure and mechanism of action.
The aim of this systematic review was to evaluate the efficacy and safety of CBD as adjunctive treatment for seizures in patients with DS using meta-analytical techniques.
We searched for randomized, placebo-controlled, single- or double-blinded trials. Main outcomes included ≥ 50% reduction in baseline convulsive seizure frequency and the incidence of treatment withdrawal and adverse events (AEs). Risk ratios (RRs) with 95% confidence intervals (95% CIs) were estimated through the inverse variance method.
Three trials were included involving 359 participants, 228 for CBD and 131 for placebo groups. In all trials, the active treatment was a plant-derived pharmaceutical formulation of purified CBD oral solution. The pooled RR for 50% response during the treatment was 1.69 (95% CI 1.21–2.36; p = 0.002). Across the trials, treatment was discontinued in 20 (9.0%) and 3 (2.3%) cases in the add-on CBD and placebo groups, respectively; the RR for CBD withdrawal was 3.12 (95% CI 1.07–9.10; p = 0.037). The RR to develop any AE during add-on CBD treatment was 1.06 (95% CI 0.87–1.28; p = 0.561). AEs significantly associated with adjunctive CBD were somnolence, decreased appetite, diarrhea, and increased serum aminotransferases.
Adjunctive CBD resulted in a greater reduction in convulsive seizure frequency than placebo and a higher rate of AEs in patients with DS presenting with seizures uncontrolled by concomitant antiepileptic therapy.
Compliance with Ethical Standards
No funding has been received for the conduct of this study.
Conflict of interest
Simona Lattanzi, Cinzia Del Giovane and Mauro Silvestrini have no conflicts of interest directly relevant to the content of this study. Francesco Brigo acted as a consultant for Eisai. Eugen Trinka has received speaker’s honoraria from UCB, Biogen, Gerot-Lannach, Bial, Eisai, Takeda, Newbridge, Sunovion Pharmaceuticals Inc., LivaNova and Novartis; consultancy funds from UCB, Biogen, Gerot-Lannach, Bial, Eisai, Takeda, Newbridge, GW Pharmaceuticals, Sunovion Pharmaceuticals Inc., and Novartis; directorship funds from Neuroconsult GmbH. E. Trinka’s Institution received grants from Biogen, Red Bull, Merck, UCB, European Union, FWF Österreichischer Fond zur Wissenschaftsförderung, and Bundesministerium für Wissenschaft und Forschung. Gaetano Zaccara has received speaker’s or consultancy fees from Eisai, Sanofi-Aventis, and UCB Pharma. Pasquale Striano has received speaker fees and participated at advisory boards for Biomarin, Zogenyx and GW Pharmaceuticals, and received research funding by ENECTA srl, GW Pharmaceuticals, Kolfarma srl. and Eisai.
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