Four ASMs (stiripentol, cannabidiol, fenfluramine, soticlestat) show high-quality evidence for efficacy and tolerability; fenfluramine superior in seizure control, cannabidiol better tolerated than fenfluramine.
Summary
Network meta-analysis across k=8 placebo-controlled RCTs (n=680) in Dravet syndrome; pharmaceutical CBD showed lower seizure response (≥50% reduction) than fenfluramine (OR=0,20; 95% CI 0,07–0,54) and lower than stiripentol (OR=14,07; 95% CI 2,57–76,87); CBD was associated with fewer adverse events than fenfluramine (OR=0,22; 95% CI 0,06–0,78); first-class evidence for efficacy and tolerability documented for all four ASMs.
P
PopulationChildren and adults with Dravet syndrome, pooled n=680 (409 active treatment, 271 placebo)
OutcomeCannabidiol with lower seizure response vs. fenfluramine (OR 0,20; 95% CI 0,07–0,54); stiripentol with higher seizure response vs. cannabidiol (OR 14,07; 95% CI 2,57–76,87); no significant differences in seizure freedom
Confidence in the evidence
Very lowLowModerateHigh
High
The highest of four GRADE levels, the effect estimate is very reliable.
Quality profile
Sample size★★★★★
BlindingDouble-blind
Effect sizeClear benefit
Citations / year★★★★★
Authors
Lattanzi S, Trinka E, Russo E, Del Giovane C, Matricardi S, Meletti S, Striano P, Damavandi PT, Silvestrini M, Brigo F
Dravet syndrome (DS) is a severe developmental and epileptic encephalopathy characterized by drug-resistant, lifelong seizures. The management of seizures in DS has changed in recent years with the approval of new antiseizure medications (ASMs). The aim of this study was to estimate the comparative efficacy and tolerability of the ASMs for the treatment of seizures associated with DS using a network meta-analysis (NMA). Eight placebo-controlled trials were included, and the active add-on treatments were stiripentol (n=2), pharmaceutical-grade cannabidiol (n=3), fenfluramine hydrochloride (n=2), and soticlestat (n=1). The studies recruited 680 participants, of whom 409 were randomized to active treatments and 271 to placebo. Pharmaceutical-grade cannabidiol was associated with a lower rate of seizure response than fenfluramine hydrochloride (OR 0.20, 95% CI 0.07-0.54), and stiripentol was associated with a higher seizure response rate than pharmaceutical-grade cannabidiol (OR 14.07, 95% CI 2.57-76.87). No statistically significant differences emerged across the different ASMs for the seizure freedom outcome. Pharmaceutical-grade cannabidiol was associated with a lower proportion of participants experiencing any AE than fenfluramine hydrochloride (OR 0.22, 95% CI 0.06-0.78). Stiripentol had a higher risk of AE occurrence than pharmaceutical-grade cannabidiol (OR 75.72, 95% CI 3.59-1598.58). The study found high-quality evidence of efficacy and tolerability of the four ASMs in the treatment of convulsive seizures in DS.