CBD significantly reduced seizure frequency and major seizures and increased seizure-free days compared to baseline.
Summary
n=45 children (1–18 years) with treatment-resistant epilepsy (TRE), CBD (Epidiolex®) up to 50 mg/kg/day adjunctive over up to 36 months; major seizure reduction 54–72% at various measurement time points (all p<0,001); total seizure reduction 61–70%; mean increase in seizure-free days >5 in all treatment periods after month 2, at endpoint +7,52 seizure-free days per 28 days (p<0,001).
P
PopulationChildren with treatment-resistant epilepsy (TRE), non-LGS/Dravet, n=45, age 1–18 years
I
InterventionPlant-derived, highly purified cannabidiol (CBD; Epidiolex) oral 100 mg/mL, up to 25 mg/kg/day (optionally up to 50 mg/kg/day), as adjunctive therapy over 36 months
O
OutcomeMedian percentage reduction in major seizures 54–72% and all seizures 61–70% vs. baseline (p<0,001); mean increase in seizure-free days by 7,52 per 28 days at end of study (p<0,001)
Confidence in the evidence
Very lowLowModerateHigh
Moderate
The third of four GRADE levels, the effect estimate is probably reliable.
Downgraded for
Imprecision
Quality profile
Sample size★★★★★
Blinding—
Effect sizeClear benefit
Citations / year★★★★★
Authors
Park YD, Linder DF, Pope J, Flamini JR, Moretz K, Diamond MP, Long SA.
<h4>Introduction</h4>An intermediate-sized, multicenter, expanded-access study was opened in 2015 through the support of the State of Georgia. This study provided children with treatment-resistant epilepsy (TRE) access to plant-derived highly purified cannabidiol (CBD; Epidiolex® in the US; Epidyolex® in the EU; 100 mg/mL oral solution). These children had failed to achieve seizure freedom with available treatment options and were ineligible to participate in randomized controlled trials that only included patients with Lennox-Gastaut and Dravet syndromes.<h4>Methods</h4>Cannabidiol safety, changes in seizure type, frequency, and seizure-free days were evaluated for children aged 1-18 years (at time of consent) as an adjunctive treatment for 36 months. The study consisted of a two-month baseline period, a titration period, treatment period, and optional titration period, which occurred after ≥26 weeks of treatment. Cannabidiol treatment was administered up to a targeted dose of 25 mg/kg/day, with an optional secondary treatment up to 50 mg/kg/day. Daily seizure type, seizure frequency, and seizure-free days were recorded in a Web-based diary, and changes in these outcomes were recorded and analyzed for the duration of the study. The occurrence of adverse events (AEs) was also recorded.<h4>Results</h4>The median percentage change in seizures for 45 patients in Months 3, 6, 12, 18, 24, and 36 showed a statistically significant (p < 0.001) reduction in major seizures (ranging from 54 to 72% at various time points) and all seizures (61-70%) compared with baseline. A mean increase in seizure-free days per 28 days was >5 in all treatment periods after Month 2, and an average increase of 7.52 (p < 0.001) seizure-free days per 28 days was observed at the end of follow-up compared with baseline. All patients experienced ≥1 AE. Children who transitioned to the optional secondary treatment (high-dose group) reported more AEs before increasing their dose to >25.0 mg/kg/day compared with the low-dose group. However, the average rate of AEs was significantly lower after moving to a high-dose regimen (p = 0.004). Twelve children reported 20 serious AEs, none of which were considered related to CBD.<h4>Conclusions</h4>This study supports CBD as an adjunctive treatment for children with TRE. Treatment was well tolerated in doses up to 50 mg/kg/day. Patients who did not achieve desired results at a dose of ≤25.0 mg/kg/day reported more AEs when CBD dose increased to >25.0 mg/kg/day. Decreases in major seizure frequency and an increase in seizure-free days compared with baseline were reported during treatment. This supports the efficacy and tolerability of CBD for mixed seizure etiologies.