Use of cannabidiol in the treatment of epilepsy: Lennox-Gastaut syndrome, Dravet syndrome, and tuberous sclerosis complex.
Silvinato et al.·Revista da Associacao Medica Brasileira (1992)Impact 1.3
MixedGRADEModerate23 citations
Samplek = 6 Studien n = 1.034 Pat.
Durationunclear
ControlPlacebo
EndpointSeizure frequency
Blindingn.a.
DesignSystematic Review / Meta-Analysis
Cannabinoidcbd
”Key finding
CBD reduces seizure frequency by 33% and increases seizure-free patients by 3%, but increases serious side effects by 16% and treatment discontinuations by 12%.
Summary
k=6 RCTs, n=1.034 patients; CBD as add-on therapy (in DS, LGS, TSC) reduced seizure frequency by 33%; proportion of responders (≥50% reduction) +20%; seizure freedom +3%; CGIC improvement +21%; serious adverse events +16%, transaminase elevation ≥3× +15%.
P
PopulationChildren and adults with Dravet syndrome (DS), Lennox-Gastaut syndrome (LGS) or tuberous sclerosis complex (TSC) and inadequate seizure control, pooled n=1.034
I
InterventionCannabidiol (CBD) as add-on therapy (adjunctive treatment)
C
ControlPlacebo
O
OutcomeCBD reduces seizure frequency by 33%; increases proportion with ≥50% reduction by 20%; improves S/CGIC score by 21%; however increases adverse events (+12%), serious AEs (+16%), treatment discontinuation (+12%) and transaminase elevation (+15%)
Confidence in the evidence
Very lowLowModerateHigh
Moderate
The third of four GRADE levels, the effect estimate is probably reliable.
The objective of this systematic review with meta-analysis was to evaluate the efficacy, safety, and short- and long-term tolerability of cannabidiol (CBD), as an adjunct treatment, in children and adults with Dravet syndrome (SD), Lennox-Gataut syndrome (LGS), or tuberous sclerosis complex (TSC), with inadequate control of seizures. This systematic review was conducted through a search for scientific evidence in the Mediline/PubMed, Central Cochrane, and ClinicalTrials.gov databases until April 2022. Selected randomized clinical trials (RCTs) that presented the outcomes: reduction in the frequency of seizures and total seizures (all types), number of patients with a response greater than or equal to 50%, change in caregiver global impression of change (CGIC) (improvement ≥1 category on the initial scale), adverse events (AEs), and tolerability to treatment. This review followed Preferred Reporting Items for Systematic reviews and Meta-Analyses. Notably, six RCTs were included, with a total of 1,034 patients with SD, LGS, and TSC, of which 3 were open-label extension RCTs. The meta-analysis of the studies showed that the use of CBD as compared with placebo, in patients with convulsive seizures refractory to the use of medications, reduces the frequency of seizures by 33%; increases the number of patients with a reduction ≥50% in the frequency of seizures by 20%; increases the number of patients with absence of seizures by 3%; improves the clinical impression evaluated by the caregiver or patient (S/CGIC) in 21%; increases total AEs by 12%; increases serious AE by 16%; increases the risk of treatment abandonment by 12%; and increases the number of patients with transaminase elevation (≥3 times the referral) by 15%. This systematic review, with meta-analysis, supports the use of CBD in the treatment of patients with seizures, originated in DS, LGS, and TSC, who are resistant to the common medications, presenting satisfactory benefits in reducing seizures and tolerable toxicity.