Study register · detailMeta-Analyse · Epilepsy · 2018
Efficacy and Safety of Adjunctive Cannabidiol in Patients with Lennox–Gastaut Syndrome: A Systematic Review and Meta-Analysis
Lattanzi et al.·CNS DrugsImpact 6.6
Clear benefitGRADEHigh61 citations
Samplek = 2 Studien n = 396 Pat.
Durationunclear
ControlPlacebo
EndpointSeizure frequency reduction…
Blindingdoppelblind
DesignMeta-Analyse
Cannabinoidcbd
”Key finding
Cannabidiol as add-on therapy led to a significantly higher rate of patients with ≥50% reduction in seizure frequency (drop and non-drop seizures) compared to placebo, however with increased risk of adverse events and study discontinuations.
Summary
Systematic review and meta-analysis of k=2 RCTs (n=396) on adjunctive CBD therapy in Lennox-Gastaut syndrome. ≥50% reduction in drop seizures in 40,0% with CBD vs. 19,3% placebo (RR: 2,12, 95%CI: 1,48–3,03; p<0,001). Non-drop seizures ≥50% reduced in 49,4% CBD vs. 30,4% placebo (RR: 1,62, 95%CI: 1,09–2,43; p=0,018). Treatment discontinuation RR: 4,93 (95%CI: 1,50–16,22; p=0,009). Adverse events RR: 1,24 (95%CI: 1,11–1,38; p<0,001).
P
PopulationPatients with Lennox-Gastaut syndrome and uncontrolled seizures under existing antiepileptic therapy, pooled n=396
I
InterventionAdjunctive cannabidiol (CBD) added to existing antiepileptics
C
ControlPlacebo
O
Outcome≥50% reduction in drop-seizure frequency: CBD 40,0% vs. placebo 19,3% [RR 2,12 (95%-CI 1,48–3,03); p<0,001]; ≥50% reduction in non-drop seizures: RR 1,62 (95%-CI 1,09–2,43; p=0,018); increased risk of discontinuation under CBD [RR 4,93 (95%-CI 1,50–16,22; p=0,009)]
Confidence in the evidence
Very lowLowModerateHigh
High
The highest of four GRADE levels, the effect estimate is very reliable.
Background: Lennox-Gastaut syndrome (LGS) is a severe developmental epileptic encephalopathy, and available interventions fail to control seizures in most patients. Cannabidiol (CBD) is a major chemical of Cannabis, which has anti-seizure properties and different mechanisms of action compared with other approved antiepileptic drugs (AEDs).
Objective: The aim was to evaluate the efficacy and safety of CBD as adjunctive treatment for seizures in patients with LGS using meta-analytical techniques.
Methods: Randomized, placebo-controlled, single- or double-blinded trials were identified. Main outcomes included the >/= 50% reduction in baseline drop and non-drop seizure frequency, and the incidence of treatment withdrawal and adverse events (AEs). Risk ratios (RRs) with 95% confidence intervals (CIs) were estimated through the inverse variance method.
Results: Two trials were included involving 396 participants. Patients presenting >/= 50% reduction in drop seizure frequency during the treatment were 40.0% with CBD and 19.3% with placebo [RR 2.12 (95% CI 1.48-3.03); p < 0.001]. The rate of non-drop seizure frequency was reduced by 50% or more in 49.4% of patients in the CBD and 30.4% in the placebo arms [RR 1.62 (95% CI 1.09-2.43); p = 0.018]. The RR for CBD withdrawal was 4.93 (95% CI 1.50-16.22; p = 0.009). The RR to develop any AE during CBD treatment was 1.24 (95% CI 1.11-1.38; p < 0.001). AEs significantly associated with CBD were somnolence, decreased appetite, diarrhea and increased serum aminotransferases.
Conclusions: Adjunctive CBD resulted in a greater reduction in seizure frequency and a higher rate of AEs than placebo in patients with LGS presenting seizures uncontrolled by concomitant AEDs.