Long-term safety and efficacy of add-on cannabidiol in patients with Lennox-Gastaut syndrome: Results of a long-term open-label extension trial.

OBJECTIVE: Lennox-Gastaut syndrome (LGS) is an epileptic encephalopathy that is often treatment resistant. Efficacy and safety of add-on cannabidiol (CBD) to treat seizures associated with LGS was demonstrated in two randomized controlled trials (RCTs). Patients who completed the RCTs were invited to enroll in this long-term open-label extension (OLE) trial, GWPCARE5 (NCT02224573). We present the final analysis of safety and efficacy outcomes from GWPCARE5. METHODS: Patients received plant-derived highly purified CBD (Epidiolex in the United States; Epidyolex in the European Union; 100 mg/ml oral solution), titrated to a target maintenance dose of 20 mg/kg/day over 2 weeks. Based on response and tolerability, CBD could then be reduced or increased up to 30 mg/kg/day. RESULTS: Of 368 patients with LGS who completed the RCTs, 366 (99.5%) enrolled in this OLE. Median and mean treatment duration were 1090 and 826 days (range = 3-1421), respectively, with a mean modal dose of 24 mg/kg/day. Adverse events (AEs) occurred in 96% of patients, serious AEs in 42%, and AE-related discontinuations in 12%. Common AEs were convulsion (39%), diarrhea (38%), pyrexia (34%), and somnolence (29%). Fifty-five (15%) patients experienced liver transaminase elevations more than three times the upper limit of normal; 40 (73%) were taking concomitant valproic acid. Median percent reductions from baseline ranged 48%-71% for drop seizures and 48%-68% for total seizures through 156 weeks. Across all 12-week visit windows, 87% or more of patients/caregivers reported improvement in the patient's overall condition on the Subject/Caregiver Global Impression of Change scale. SIGNIFICANCE: Long-term add-on CBD treatment had a similar safety profile as in the original RCTs. Sustained reductions in drop and total seizure frequency were observed for up to 156 weeks, demonstrating long-term benefits of CBD treatment for patients with LGS.

Healthcare professionals' knowledge, attitude, and perception of epilepsy surgery: A systematic review.

OBJECTIVE: The epilepsy surgery treatment gap is well defined and secondary to a broad range of issues, including healthcare professionals' (HCPs') knowledge, attitude, and perception (KAP) toward epilepsy surgery. However, no previous systematic reviews investigated this important topic. METHODS: The systematic review was conducted according to Preferred Reporting Items for the Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We identified a total of 652 articles from multiple databases using database-specific queries and included 65 articles for full-text review after screening the titles and abstracts of the articles. Finally, we selected 11 papers for qualitative analysis. We critically appraised the quality of the studies using the Joanna Briggs critical appraisal tool. RESULTS: The qualitative analysis of the content identified several key reasons causing healthcare professional-related barriers to epilepsy surgery: inadequate knowledge and awareness about the role of epilepsy surgery in drug-resistant epilepsy (DRE), poor identification and referral of patients with DRE, insufficient selection of candidates for presurgical workup, negative or ambivalent attitudes and perceptions regarding epilepsy surgery, deficient communication practices with patients regarding risk-benefit analysis of epilepsy surgery, and challenging coordination issues with the surgical referral. Neurologists with formal instruction in epilepsy, surgical exposure during training, participation in high volume epilepsy practice, or prior experience in surgical referral may refer more patients for surgical evaluation. CONCLUSIONS: While significant work has been conducted in a limited number of studies to explore HCPs' knowledge gap and educational need regarding epilepsy surgery, further research is needed in defining the learning goals, assessing and validating specific learning gaps among providers, defining the learning outcomes, optimizing the educational format, content, and outcome measures, and appraising the achieved results following the educational intervention.