Real-world efficacy and safety of cannabidiol in developmental and epileptic encephalopathies
Marco Perulli, Maddalena Bianchetti, Gloria Pantalone, Michela Quintiliani, Maria Luigia Gambardella, Maria Picilli, Carla Marini, Elisabetta Cesaroni, Domenica Immacolata Battaglia
| Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy Child Neurology and Psychiatric Unit, Pediatric Hospital G. Salesi, Azienda Ospedaliero-Universitaria Delle Marche, Ancona, Italy Università Cattolica del Sacro Cuore, Rome, Italy Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy Child Neurology and Psychiatric Unit, Pediatric Hospital G. Salesi, Azienda Ospedaliero-Universitaria Delle Marche, Ancona, Italy |
Affiliationer
Objective
Highly 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.
Methods
In 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.
Results
Patients 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.
Significances
This 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 summary
This 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.
Key points
- After a median follow-up of 20 months, CBD was globally effective and safe in 107 patients with LGS, DS, TSC, and other DEEs.
- Efficacy (>50% seizure reduction) and retention rate at the most recent follow-up were respectively 69.0% and 66.4%.
- Patients with DS showed relatively lower efficacy compared to other groups, including off-label indication.
- Concomitant valproate treatment correlated with lower efficacy, while clobazam had no relation to efficacy or safety.
- Positive non-seizure results included improved alertness, sleep quality, and enhanced motor performance.
