A systematic review of highly purified cannabidiol in developmental and epileptic encephalopathies and complex treatment-resistant epilepsies: Changes in seizure frequency and adverse events

OBJECTIVE: The efficacy and safety of a highly purified plant-derived cannabidiol (CBD) oral solution (Epidiolex® [US]/Epidyolex® [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.