Effect of Cannabidiol on Interictal Epileptiform Activity and Sleep Architecture in Children with Intractable Epilepsy: A Prospective Open-Label Study.

BACKGROUND: Cannabidiol has been shown to be effective in seizure reduction in patients with Dravet syndrome, Lennox-Gastaut syndrome, and tuberous sclerosis. However, very little is known about its potential to reduce interictal epileptiform activity and improve sleep architecture. OBJECTIVE: The objective of this prospective study was to evaluate the influence of cannabidiol therapy on the frequency of interictal epileptiform discharges (IEDs) and sleep microstructure in a cohort of children with drug-resistant epilepsy. METHODS: Children with drug-resistant epilepsy were prospectively followed from November 2019 to January 2021 during an open-label trial of cannabidiol at a dose of 20 mg/kg/day (to a maximum of 50 mg/kg/day) and stable concomitant medication. Electroencephalograms were recorded at baseline (T0) and after 3 months (T1). Two independent raters, blinded to clinical outcome, evaluated 5-min segments of sleep stage 2 or low-noise awake state. IEDs were visually identified and rates per minute calculated. Sleep microstructure was considered improved if sleep structures were seen at T1 that were not present at T0. IED rates at T0 and T1 were compared and correlated with seizure outcome, cannabidiol dose, initial IED rate, and disease duration. RESULTS: In total, 35 children (mean ± standard deviation age 10.1 ± 0.86) were included. The IED rate at T1 was significantly lower than at T0 (19.6 ± 19.5 vs. 36.8 ± 27.2, respectively; p < 0.0001). We found a moderate correlation between IED reduction and percentage of seizure reduction compared with baseline (Pearson's r = 0.39; p = 0.02), a moderate negative correlation between IED reduction and IED rate at T0 (r = - 0.34; p = 0.04), and a trend towards a moderate negative correlation between IED reduction and disease duration (r = - 0.32; p = 0.06). Sleep was recorded in 23 patients. Sleep microstructure was initially abnormal in 56.5% of sleep recordings and improved in 84.6% of those cases. CONCLUSION: Our results strongly suggest the utility of cannabidiol in reducing IEDs and improving sleep microstructure in children with drug-resistant epilepsy. Larger controlled studies are needed to evaluate the clinical relevance of this effect in different epilepsy types. TRIAL REGISTRATION: DRKS00013177; 25 June 2019.

Efficacy and Tolerance of Synthetic Cannabidiol for Treatment of Drug Resistant Epilepsy.

Objective: Controlled and open label trials have demonstrated efficacy of cannabidiol for certain epileptic encephalopathies. However, plant derived cannabidiol products have been used almost exclusively. Efficacy of synthetically derived cannabidiol has not been studied before. The objective of this study was to evaluate tolerability and efficacy of synthetic cannabidiol in patients with pharmacoresistant epilepsy. Methods: In this prospective, open-label study (DRKS00013177), patients with pharmacoresistant epilepsy received synthetic cannabidiol in addition to their previously stable anticonvulsive treatment. Starting dose was 5 mg/kg/day, up-titrated to a maximum of 50 mg/kg/day. Primary efficacy endpoint was monthly frequency of motor seizures at 3 months. Results: Between April 2017 and May 2019, 35 patients were enrolled in the study. Mean age was 19.7 years (SD 14.6). Median motor seizure frequency decreased from 21.8 (IQR 7.5-52.5) seizures per month at baseline to 8.5 (IQR 3.7-28.3, p < 0.001) at 3 months, effect not influenced by AED changes and drop-outs. Adjusted percentage reduction was 40.0% (IQR 18.2-58.5). Adverse events (AE) were reported in 25 patients (71.4%), most frequently somnolence (40%), diarrhea (34.3), and loss of appetite (20%). Two patients (5.7%) discontinued treatment due to AE. Median (range) of treatment duration was 321 days (range 36-824). With ongoing treatment up to date in 21 patients (60%). Conclusion: Efficacy and tolerance in our study of synthetic CBD treatment in pharmacoresistant epilepsy is similar to open label studies using plant derived CBD. Regarding economic and ecological aspects, synthetic cannabidiol might be a reasonable alternative to plant derived cannabidiol.