Nonseizure- and seizure-related benefits of cannabidiol treatment in the real world: plain language summary of the results from a caregiver survey

Fenfluramine treatment beyond dravet and lennox-gastaut syndromes - A retrospective study suggesting a novel use in genetic, developmental and epileptic encephalopathies (DEEs).

Ketogenic diet therapies have proven efficacy for refractory epilepsy. There are many reports of their use in the genetic developmental and epileptic encephalopathies; however, little attention has been paid as to whether the diet is also effective in individuals with an acquired structural aetiology. We observed remarkable efficacy of the diet in two patients with hypoxic-ischaemic encephalopathy. We then analysed our cases with refractory structural epilepsies of acquired origin to characterize their response to the ketogenic diet. The classical ketogenic diet was implemented with dietary ratios of 3:1 to 4.4:1. Seizure frequency at 1month, 3months, 6months, 1year, and 2years was ascertained. A responder was defined as greater than 50% seizure reduction compared to baseline. Seven of the nine patients were responders at 3months. Somewhat surprisingly we found that the ketogenic diet was effective in patients with a developmental and epileptic encephalopathy due to an acquired structural aetiology. This cohort may not be routinely considered for the ketogenic diet because of their structural and acquired, rather than genetic, basis. The ketogenic diet should be considered early in the management of patients with acquired structural encephalopathies as it can improve seizure control with the potential to improve developmental outcome. The ketogenic diet was effective in children with epilepsy associated with an acquired structural aetiology.

ObjectiveTo assess the burden of Dravet syndrome (DS) and Lennox–Gastaut syndrome (LGS), including managing seizure and nonseizure symptoms, on patients and caregivers.MethodsData were drawn from the Adelphi Real World DS and LGS Disease Specific Programme™, a cross‐sectional survey in Asia (China, Japan), Europe (France, Germany, Italy, Spain, United Kingdom), and the United States of America between July 2022 and August 2023. Neurologists/pediatric neurologists reported demographics, clinical characteristics, and nonseizure symptoms for up to 10 consecutively consulting patients. Caregivers provided data on patient nonseizure symptoms, quality of life (QoL), satisfaction with treatment, and caregiver burden. Analyses were descriptive.ResultsPhysicians (n = 259) reported data on 547 patients with DS and 811 with LGS. Caregivers (n = 348) provided data on 157 patients with DS and 191 with LGS. In the previous 6 months, 51% of patients with DS experienced ≥1 seizure‐related injury and 61% experienced status epilepticus. For LGS, this was 50% and 43% of patients, respectively. Rates of moderate to very severe impairment in nonseizure symptoms were reported by physicians in learning/intellect (DS 69%; LGS 78%), verbal communication (DS 69%; LGS 71%), severity of developmental delay (DS 65%; LGS 68%), overall mental status (DS 57%; LGS 67%), and nonverbal communication (DS 61%; LGS 64%). Caregivers reported moderate to very severe impairment in learning/intellect (DS 53%; LGS 67%), severity of developmental delay (DS 52%; LGS 56%), verbal communication (DS 48%; LGS 48%), and nonverbal communication (DS 42%; LGS 45%). Caregivers reported nonseizure symptoms moderately to significantly impacted QoL for 56% of patients (DS 49%; LGS 61%); satisfaction with treatment rate was low for control over cognition/memory, verbal communication, and nonverbal communication impairment.SignificanceIn this study, considerable burden in DS and LGS management and care was driven by nonseizure symptoms, suggesting a need for treatments that manage the broad spectrum of disease symptoms.Plain Language SummaryWe asked doctors and caregivers to tell us about the symptoms that patients with Dravet syndrome and Lennox–Gastaut syndrome have. We asked how the symptoms affect the lives of the patients as well as the caregivers. We found that seizures have a big impact on the health and well‐being of patients and caregivers. We also found that other symptoms not caused by seizures have a big impact on patients and their caregivers.

Raising the bar: Fenfluramine sets new treatment standards for Dravet syndrome

The direct cost of seizure events in severe childhood-onset epilepsies: A retrospective claims-based analysis

Clinical efficacy and safety of cannabidiol for pediatric refractory epilepsy indications: A systematic review and meta-analysis

Following the approval of Epidiolex® (cannabidiol; CBD) for the treatment of seizures associated with Lennox-Gastaut syndrome (LGS), Dravet syndrome (DS), and tuberous sclerosis complex (TSC), healthcare professionals (HCPs) have had substantial experience in treating patients with Epidiolex. However, confusion still remains among HCPs, caregivers, and patients regarding dosing, drug interactions, safety monitoring, and differentiation between Epidiolex and nonapproved CBD products. To establish consensus recommendations for Epidiolex treatment optimization in LGS, DS, and TSC, a panel of seven HCPs with expertise in epilepsy was convened. Panelists participated in a premeeting survey based on a literature review of Epidiolex for the treatment of LGS, DS, and TSC, and survey responses were compiled for discussion. A modified Delphi method was used to assess agreement among panelists regarding recommendation statements following two rounds of discussion. Panelists identified two broad themes - overcoming barriers to initiation and optimization of treatment for seizures associated with LGS, DS, and TSC - for consensus guidelines. Accurate identification of patients with these rare epilepsies is critical for optimization of Epidiolex treatment. Providers should differentiate Epidiolex from nonapproved CBD products and set expectations for the therapeutic effect and safety/tolerability of Epidiolex. Initial target dose and titration rate should be individualized by baseline variables, prior response to antiseizure medications, and therapeutic goals. Awareness of strategies to manage adverse events and concomitant medications, including drug-drug interactions, is critical. Tracking response to the maximum tolerated dose is an important measure of effectiveness. These consensus recommendations provide real-world experience from neurology HCPs with experience in prescribing Epidiolex and can inform optimal use of Epidiolex for the treatment of seizures associated with LGS, DS, and TSC. PLAIN LANGUAGE SUMMARY: Epidiolex® (cannabidiol) is approved for treating seizures in Lennox-Gastaut syndrome, Dravet syndrome, and tuberous sclerosis complex. Although healthcare professionals have experience in treating patients with Epidiolex, there is a need for better understanding of dosing, drug interactions, and safety of this drug. Therefore, a group of epilepsy experts developed guidelines for best practices in Epidiolex treatment. Two main areas were identified: overcoming barriers to starting Epidiolex and considerations related to Epidiolex dosing. Within these areas, topics, including correct disease identification, managing adverse events, and determining individualized dose, were discussed. These guidelines provide real-world experience to inform optimal Epidiolex use.

Background and ImportanceCannabidiol is approved in Europe as adjunctive therapy for preventing seizures associated with Lennox-Gastaut Syndrome (LGS), Dravet Syndrome (DS), and Tuberous Sclerosis Complex (TSC) in patients with previous...

ObjectiveHighly purified cannabidiol (CBD) is approved as adjunctive therapy for seizures associated with Dravet syndrome (DS), Lennox–Gastaut syndrome (LGS), and tuberous sclerosis complex (TSC), although its role in other developmental and epileptic encephalopathies (DEEs) remains unexplored. The aim of this study was to assess the real‐world use, efficacy, and safety of CBD across a broad cohort of patients with DEEs, including off‐label indications.MethodsIn this retrospective study, we evaluated 107 patients with DEEs treated with CBD for ≥3 months between 2020 and 2024. Data on seizure frequency, tolerability, retention, and non‐seizure outcomes were collected. Efficacy was defined as ≥50% or ≥75% seizure reduction. Statistical analyses explored predictors of response.ResultsPatients had LGS (55.1%), DS (16.8%), TSC (8.4%), or other DEEs (19.6%), with a genetic etiology in 56.1%. At a median follow‐up of 20 months, 69% achieved ≥50% seizure reduction, and 21% achieved ≥75% reduction. Patients with LGS, TSC, and other DEEs showed higher efficacy and retention rates compared to DS. Genetic or unknown etiology was associated with better outcomes (p = 0.011). Combination with valproate was associated with reduced efficacy (p = 0.006), while combination with clobazam had no significant effect on efficacy nor safety. Non‐seizure improvements included increased alertness (56%), improved sleep quality (25%), and enhanced motor performance (14%). Adverse events occurred in 33.6%, mostly mild and transient; 9% discontinued due to side effects.SignificancesThis study confirms the effectiveness and good tolerability of CBD in a real‐world DEE population, including off‐label use. These findings support expanding CBD indications and underscore the need for prospective studies targeting both seizure and developmental outcomes.Plain language summaryThis study looked at the use of cannabidiol (CBD), a cannabis‐based medicine, in 107 people with severe forms of epilepsy called developmental and epileptic encephalopathies (DEEs). With CBD add‐on, about two‐thirds of patients had fewer seizures, and some caregivers noticed improvements in alertness, sleep, or movement. Most patients tolerated the treatment well, but some experienced side effects, and a few had to stop taking it. While the results are promising, more research is needed to confirm how effective and safe CBD is for different types of DEEs, especially those not currently approved for treatment with CBD.

IntroductionEffectiveness and tolerability of plant-derived highly purified cannabidiol (CBD) in patients with Lennox–Gastaut syndrome (LGS), Dravet syndrome (DS), or tuberous sclerosis complex (TSC)-associated epilepsy in clinical practice in Germany were evaluated.MethodsThis multicenter, retrospective, chart review study analyzed patients with LGS, DS, or TSC-associated epilepsy receiving ≥ 1 dose of adjunctive CBD (Epidyolex® 100 mg/mL oral solution). Treatment characteristics, seizure outcomes, physician-rated Clinical Global Impression of Change (CGI-C), treatment retention rates, and adverse events (AEs) were analyzed ≤ 12 months.ResultsAmong 202 patients identified (159 LGS; 34 DS; 9 TSC), median (interquartile range; range) age was 18.0 (7.9–32.0; 0.3–72.0) years, and median (range) number of prior and concomitant antiseizure medications was 6 (1–24) and 3 (1–7), respectively. Median target CBD dose was 11.1 mg/kg/day (17.6, 15.2, and 9.9 mg/kg/day in the < 6, 6–17, and ≥ 18 years subgroups, respectively). Responder rates (≥ 50% seizure reduction) for total seizures at 3 (n = 194) and 12 (n = 168) months were 43.3% (37.0–50.0% across ages) and 44.0% (37.0–52.5% across ages), respectively, and for generalized tonic–clonic seizures 54.3% (n = 94) (50.0–66.7% across ages) and 47.7% (n = 88) (37.8–66.7% across ages), respectively. Median (range) number of seizure days per month significantly decreased from 30 (0.3–30) to 18 (0–30) in the 3 months before the last 3 months of CBD treatment (p < 0.001). Any improvement in CGI-C was observed in 62% of patients. Of those with available data at 3 and 12 months, 89.6% and 67.1% remained on CBD, respectively. Retention was similar across age groups. AEs reported in ≥ 5% of patients were sedation and diarrhea.ConclusionsIn patients with LGS, DS, or TSC-associated epilepsy, adjunctive CBD was associated with a reduction in seizure frequency across age groups. CBD demonstrated tolerability consistent with its known profile, and 67% of patients remained on treatment at 12 months.Graphical Supplementary InformationThe online version contains supplementary material available at 10.1007/s40120-025-00788-w.

Caregiver-reported outcomes with real-world use of cannabidiol in Lennox-Gastaut syndrome and Dravet syndrome from the BECOME survey

ObjectiveTo increase understanding of the impact of cannabidiol (CBD) on outcomes beyond seizure control among individuals with Dravet syndrome or Lennox-Gastaut syndrome.MethodsQualitative interviews were conducted with caregivers of individuals with Dravet syndrome or Lennox-Gastaut syndrome treated with plant-derived, highly purified CBD medicine (Epidiolex in the USA; Epidyolex in Europe; 100 mg/mL oral solution). Symptoms and impacts of Dravet syndrome and Lennox-Gastaut syndrome on individuals were explored, as were the effects of CBD. Data were analyzed using thematic analysis.ResultsTwenty-one caregivers of individuals with Dravet syndrome (n = 14) and Lennox-Gastaut syndrome (n = 7) aged 4-22 years participated. Health-related quality of life improvements associated with CBD included cognitive function, communication, behavior, mobility, and participation in daily activities. Seizure frequency reduction was commonly reported (n = 12), resulting in caregivers having greater freedom and family life being less disrupted. Adverse events were reported by 10 caregivers.ConclusionIn addition to reduced seizure frequency, CBD may have a wide range of beneficial effects beyond seizure control that warrant further investigation.

BackgroundCannabidiol (CBD), which is one major constituent of the Cannabis sativa plant, has anti-seizure properties and does not produce euphoric or intrusive side effects. A plant-derived, highly purified CBD formulation with a known and constant composition has been approved by the US Food and Drug Administration for the treatment of seizures associated with Dravet syndrome, Lennox–Gastaut syndrome, and tuberous sclerosis complex. In the European Union, the drug has been authorized by the European Medicines Agency for the treatment of seizures associated with Dravet syndrome and Lennox–Gastaut syndrome, in conjunction with clobazam, and is under regulatory review for the treatment of seizures in patients with tuberous sclerosis complex.ObjectivesThis systematic review aimed to summarize the currently available body of knowledge about the use of this US Food and Drug Administration/European Medicines Agency-approved oral formulation of pharmaceutical-grade CBD in patients with epileptic conditions, especially developmental and epileptic encephalopathies other than Dravet syndrome and Lennox–Gastaut syndrome.MethodsThe relevant studies were identified through MEDLINE and the US National Institutes of Health Clinical Trials Registry in October 2020. There were no date limitations or language restrictions. The following types of studies were included: clinical trials, cohorts, case-control, cross-sectional, clinical series, and case reports. Participants had to meet the following criteria: any sex, any ethnicity, any age, diagnosis of epilepsy, receiving plant-derived, highly purified (> 98% w/w) CBD in a sesame oil-based oral solution for the treatment of seizures. Data extracted from selected records included efficacy, tolerability, and safety outcomes.ResultsFive hundred and seventy records were identified by database and trial register searching. Fifty-seven studies were retrieved for detailed assessment, of which 42 were eventually included for the review. The participants of the studies included patients of both pediatric and adult age. Across the trials, purified CBD was administered at dosages up to 50 mg/kg/day. In a randomized double-blind controlled trial in patients with tuberous sclerosis complex, CBD was associated with a significantly greater percent reduction in seizure frequency than placebo over the treatment period. Open-label studies suggested the effectiveness of CBD in the treatment of children and adults presenting with other epilepsy syndromes than those addressed by regulatory trials, including CDKL5 deficiency disorder and Aicardi, Dup15q, and Doose syndromes, SYNGAP1 encephalopathy, and epilepsy with myoclonic absences. The most common adverse events observed during treatment with CBD included somnolence, decreased appetite, diarrhea, and increased serum aminotransferases.ConclusionsThe currently available data suggest that response to treatment with a highly purified, plant-derived CBD oil-based solution can be seen in patients across a broad range of epilepsy disorders and etiologies. The existing evidence can provide preliminary support for additional research.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40263-021-00807-y.

What have we learned from the real-world efficacy of FFA in DS and LGS? A post-marketing study in clinical practice

Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS) are rare developmental and epileptic encephalopathies associated with seizure and nonseizure symptoms. A comprehensive understanding of how many individuals are affected globally, the diagnostic journey they face, and the extent of mortality associated with these conditions is lacking. Here, we summarize and evaluate published data on the epidemiology of DS and LGS in terms of prevalence, incidence, diagnosis, genetic mutations, and mortality and sudden unexpected death in epilepsy (SUDEP) rates. The full study protocol is registered on PROSPERO (CRD42022316930). After screening 2172 deduplicated records, 91 unique records were included; 67 provided data on DS only, 17 provided data on LGS only, and seven provided data on both. Case definitions varied considerably across studies, particularly for LGS. Incidence and prevalence estimates per 100 000 individuals were generally higher for LGS than for DS (LGS: incidence proportion = 14.5-28, prevalence = 5.8-60.8; DS: incidence proportion = 2.2-6.5, prevalence = 1.2-6.5). Diagnostic delay was frequently reported for LGS, with a wider age range at diagnosis reported than for DS (DS, 1.6-9.2 years; LGS, 2-15 years). Genetic screening data were reported by 63 studies; all screened for SCN1A variants, and only one study specifically focused on individuals with LGS. Individuals with DS had a higher mortality estimate per 1000 person-years than individuals with LGS (DS, 15.84; LGS, 6.12) and a lower median age at death. SUDEP was the most frequently reported cause of death for individuals with DS. Only four studies reported mortality information for LGS, none of which included SUDEP. This systematic review highlights the paucity of epidemiological data available for DS and especially LGS, demonstrating the need for further research and adoption of standardized diagnostic criteria.