Clinical efficacy and safety of cannabidiol for pediatric refractory epilepsy indications: A systematic review and meta-analysis.
Talwar et al.·Experimental NeurologyImpact 3.5
Clear benefitGRADEHigh58 citations
Samplek = 6 Studien
Durationup to 16 weeks
ControlPlacebo
EndpointSeizure frequency
Blindingn.a.
DesignSystematische Review + Meta-Analyse
Cannabinoidcbd
Routeoral
”Key finding
CBD showed significantly higher odds of ≥50% seizure reduction compared to placebo (OR=2.45), with consistent effects across Dravet, Lennox-Gastaut, and tuberous sclerosis syndrome.
Summary
Systematic review + meta-analysis across 6 RCTs on oral CBD (Epidiolex 10–50 mg/kg/day) in pediatric refractory epilepsy (Dravet syndrome, Lennox-Gastaut syndrome, tuberous sclerosis complex); pooled OR for ≥50% seizure reduction vs. placebo: OR=2,45 (95% CI 1,81–3,32, p<0,01). Subgroup analyses: DS OR=2,26 (95% CI 1,38–3,70), LGS OR=2,98 (95% CI 1,83–4,85), TSC OR=1,99 (95% CI 1,06–3,76). Increased adverse events vs. placebo (OR=1,81, 95% CI 1,33–2,46); all 6 RCTs with low risk of bias.
P
PopulationChildren and adults with treatment-refractory epilepsy (Dravet syndrome, Lennox-Gastaut syndrome, tuberous sclerosis complex), pooled from 6 RCTs
I
InterventionOral, highly purified cannabidiol (Epidiolex, 10–50 mg/kg/day) over up to 16 weeks
C
ControlPlacebo
O
OutcomeCBD significantly more effective than placebo (OR = 2,45, 95% CI = 1,81–3,32, p < 0,01); subgroup analysis: DS OR = 2,26, LGS OR = 2,98, TSC OR = 1,99; increased adverse events (OR = 1,81) and serious adverse events (OR = 2,86) under CBD
Confidence in the evidence
Very lowLowModerateHigh
High
The highest of four GRADE levels, the effect estimate is very reliable.
Antiseizure medications (ASMs) are the mainstay for the treatment of seizure disorders. However, about one-third of people with epilepsy remain refractory to current ASMs. Cannabidiol (CBD) has recently been approved as ASM for three refractory epilepsy syndrome indications in children and adults. In this study, we evaluated the overall clinical potential of an oral CBD to treat refractory epilepsy in patients with Dravet syndrome (DS), Lennox-Gastaut syndrome (LGS), and tuberous sclerosis complex (TSC) through a systematic review and meta-analysis. A comprehensive search of databases was conducted, including randomized controlled trials (RCTs) assessing the effect of CBD in epilepsy patients. The review was conducted as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The review focused on RCTs involving patients receiving highly purified oral CBD (Epidiolex, 10 to 50 mg/kg/day) for up to 16 weeks. A subgroup analysis by syndrome and CBD with or without concomitant clobazam was conducted. The key outcomes were reduction in seizure frequency, differences in 50% responder rates, adverse events, and interactions with clobazam as co-therapy. Odds ratio (OR) with 95% confidence interval (CI) were estimated. Of 1183 articles screened, we included 6 RCTs meeting our eligibility criteria. All studies were considered to have a low risk of bias. In the pooled analysis, CBD treatment was found to be more efficacious compared to placebo (OR = 2.45, 95% CI = 1.81-3.32, p < 0.01). Subgroup analysis by syndrome demonstrated the odds of ≥50% reduction in seizures with CBD treatment in patients with DS (OR = 2.26, 95% CI: 1.38-3.70), LGS (OR = 2.98, 95% CI: 1.83-4.85) and TSC (OR = 1.99, 95% CI = 1.06-3.76). Compared with placebo, CBD was associated with increased adverse events (OR = 1.81, 95% CI = 1.33-2.46) such as diarrhea, somnolence, and sedation, and any serious adverse events (OR = 2.86, 95% CI = 1.63-5.05). Other factors, including dosage and clobazam co-therapy, were significantly associated with a greater effect on seizure control and side effects of CBD. In conclusion, the study shows that CBD is highly efficacious both as standalone and adjunct therapy with clobazam for controlling seizures in DS, LGS, and TSC conditions while limiting side effects.