Among 82 patients with severe Dravet or Lennox-Gastaut syndrome who had failed a median of 8 prior medications, 40.2% achieved at least 50% seizure reduction with purified CBD within 3 months.
Neurologists treating refractory epilepsy, families of patients with Dravet or Lennox-Gastaut syndrome.
40.2% achieved ≥50% seizure reduction after failing median 8 prior drugs
What the researchers found
At 3 months, 40.2% of patients achieved 50% or greater seizure reduction, with 1.2% becoming seizure-free. Retention rates were similar for Dravet and Lennox-Gastaut syndromes but higher in adults than pediatric patients. Of 93 enrolled patients, 31.2% dropped out (17.2% for lack of efficacy, 12.9% for adverse events). Most common side effects were somnolence (22.6%) and diarrhea (11.9%).
Why it matters
These patients represent the most treatment-resistant cases, having failed a median of 8 medications. Achieving 50% seizure reduction in 40% of this population is clinically meaningful, and the real-world expanded access design provides pragmatic evidence beyond controlled trials.
The numbers in context
93 enrolled, 82 analyzed. Median 8 failed prior medications. 50% seizure reduction: 40.2%. Seizure-free: 1.2%. Dropout: 31.2%. Somnolence: 22.6%. Diarrhea: 11.9%. Transaminase elevation noted. CBD coadministered with valproic acid (62.2%) and clobazam (41.5%).
How the study worked
Open-label prospective expanded access program across 30 Italian centers (December 2018 to December 2019). Purified CBD up to 25 mg/kg/day added to existing medications. 93 patients enrolled for safety analysis, 82 with at least 3 months follow-up for effectiveness. Median 8 previously failed antiseizure medications.
What this study cannot tell us
Open-label design with no placebo group. Potential placebo effect. Only 3 months of effectiveness data. Concurrent medication changes possible. Dropout rate of 31% may bias results.
How to read the evidence
Multicenter prospective design in a real-world setting, but open-label with no placebo control.
When this study was published
2021 interim results from Italian expanded access program (2018-2019).
The bigger picture
This Italian EAP adds to the global evidence supporting CBD for treatment-resistant epilepsy. The finding that effectiveness was independent of clobazam use is important, as some have questioned whether CBD benefits in epilepsy are partly mediated through clobazam interactions.
Questions still open
- Do seizure reduction rates improve or decline beyond 3 months? Which patients are most likely to respond? Is the benefit maintained when adjusting concurrent medications?
Common questions
Did CBD work independently of clobazam?
What were the main side effects?
Read the original research
Results From an Italian Expanded Access Program on Cannabidiol Treatment in Highly Refractory Dravet Syndrome and Lennox-Gastaut Syndrome.
Frontiers in neurology, 12, 673135
Citation
Iannone, Luigi Francesco; Arena, Gabriele; Battaglia, Domenica; Bisulli, Francesca; Bonanni, Paolo; Boni, Antonella; Canevini, Maria Paola; Cantalupo, Gaetano; Cesaroni, Elisabetta; Contin, Manuela; Coppola, Antonietta; Cordelli, Duccio Maria; Cricchiuti, Giovanni; De Giorgis, Valentina; De Leva, Maria Fulvia; De Rinaldis, Marta; d'Orsi, Giuseppe; Elia, Maurizio; Galimberti, Carlo Andrea; Morano, Alessandra; Granata, Tiziana; Guerrini, Renzo; Lodi, Monica A M; La Neve, Angela; Marchese, Francesca; Masnada, Silvia; Michelucci, Roberto; Nosadini, Margherita; Pilolli, Nicola; Pruna, Dario; Ragona, Francesca; Rosati, Anna; Santucci, Margherita; Spalice, Alberto; Pietrafusa, Nicola; Striano, Pasquale; Tartara, Elena; Tassi, Laura; Papa, Amanda; Zucca, Claudio; Russo, Emilio; Mecarelli, Oriano. (2021). Results From an Italian Expanded Access Program on Cannabidiol Treatment in Highly Refractory Dravet Syndrome and Lennox-Gastaut Syndrome.. Frontiers in neurology, 12, 673135. https://doi.org/10.3389/fneur.2021.673135
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