CBD reduced seizures in both Dravet and Lennox-Gastaut syndromes, with enhanced effects when combined with clobazam

CBD reduced primary seizure frequency versus placebo in LGS (treatment ratio 0.70) and Dravet syndrome (0.71) in the overall population. Effects were larger in patients on clobazam (LGS: 0.56; DS: 0.63). CBD improved 50% responder rates, total seizure frequency, seizure-free days, and global impression of change. Somnolence and sedation were more common with CBD plus clobazam. Elevated transaminases occurred mainly in patients on concomitant valproate.

Subgroup analysis of patients on clobazam and meta-analysis by syndrome across four randomized, placebo-controlled phase 3 trials of pharmaceutical-grade CBD (Epidiolex/Epidyolex; 10 or 20 mg/kg/day for 14 weeks). 396 LGS patients (49% on clobazam) and 318 DS patients (64% on clobazam).

This meta-analysis directly addresses the critical question of whether CBD's seizure reduction is partly driven by its interaction with clobazam, showing CBD is effective in both clobazam users and the overall population, but more so in the combination.

The enhanced effect with clobazam is clinically important: it means the combination may be more effective than either alone, but clinicians need to manage the increased sedation and monitor liver enzymes, especially with valproate co-administration.

Post-hoc subgroup analysis, not pre-specified in original trials. Cannot fully separate CBD's direct effects from clobazam interaction effects. 14-week treatment period may not reflect long-term outcomes. Industry-sponsored trials.