Study register · detailSystematic Review · Epilepsy · 2026
A systematic review of highly purified cannabidiol in developmental and epileptic encephalopathies and complex treatment-resistant epilepsies: Changes in seizure frequency and adverse events.
Coppola et al.·Epilepsy researchImpact 1.8
Clear benefitGRADEHigh2 citations
Samplek = 57 Studien n = 971 Pat.
Durationunclear
EndpointSeizure frequency
Blindingunklar
DesignSystematic Review
Cannabinoidcbd
Routeoral
”Key finding
CBD reduced seizure frequency in patients with various DEEs and complex treatment-resistant epilepsies; 47 of 57 studies reported seizure reduction in at least one patient.
Summary
Systematic review of highly purified CBD (Epidiolex) in 37 rare developmental/epileptic encephalopathies and complex treatment-refractory epilepsies; k=57 studies (mostly case reports/small series), n=971 patients. 47 studies reported seizure reduction (20–100% of patients), 22 studies ≥1 seizure-free patient (≥48 days). Most common adverse effects: diarrhea (17–50%), decreased appetite (7–45%), vomiting (5–86%).
P
PopulationPatients with developmental and epileptic encephalopathies (DEEs) as well as complex treatment-resistant epilepsies (TREs), pooled n=971
I
InterventionHighly purified plant-derived cannabidiol (CBD) oral (Epidiolex/Epidyolex), various dosages
O
OutcomeIn 47 of 57 studies a reduction in seizure frequency was reported in ≥1 patient; seizure reduction 20–100 % of patients (18 studies); mean/median percentage seizure reduction 12–99 % (8 studies); 22 studies reported ≥1 seizure-free patient for ≥48 days
Confidence in the evidence
Very lowLowModerateHigh
High
The highest of four GRADE levels, the effect estimate is very reliable.
Objective: The efficacy and safety of a highly purified plant-derived cannabidiol (CBD) oral solution (Epidiolex(R) [US]/Epidyolex(R) [EU], EPX) have been established for the treatment of seizures in patients with Lennox-Gastaut syndrome, Dravet syndrome, or tuberous sclerosis complex. These conditions involve diverse etiologies, suggesting EPX may have broad utility across different seizure types. This systematic literature review (SLR) evaluated studies reporting CBD effectiveness and tolerability in patients with other developmental and epileptic encephalopathies (DEEs) and complex treatment-resistant epilepsies (TREs).
Methods: In accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, an SLR was conducted in March 2024 using Embase, PubMed, and Cochrane libraries for publications on complex TREs, CBD, seizure outcomes, and adverse events (AEs). Results were narratively summarized according to epilepsy type.
Results: Seizure frequency-related changes were reported in 57 studies including 37 DEEs/TREs comprising 971 patients; most (n = 33) were case reports/small case series. Most common diagnoses were focal/multifocal-onset epilepsy (n = 401) and Angelman syndrome (n = 188). Overall, 47 studies reported seizure frequency reduction in >/= 1 patient; definitions/thresholds included seizure reduction (n = 18 studies; 20-100 % of patients) and mean/median percent seizure reduction (n = 8 studies; 12-99 % reduction). Twenty-two studies reported >/= 1 patient was seizure-free for >/= 48 days. AEs experienced while taking CBD were generally mild or moderate and most commonly gastrointestinal, including diarrhea (17-50 %), decreased appetite (7-45 %), and vomiting (5-86 %).
Conclusion: CBD may reduce seizure frequency in patients with a range of DEEs and complex TREs. These findings support future studies in these populations.