Background: Lennox–Gastaut syndrome is a catastrophic pediatric epilepsy syndrome characterized by multiple types of treatment-resistant seizures and high rates of seizure-related injury. Current available treatments are inadequate, leaving patients with few treatment options and opportunities.

Methods: We conducted a double-blind, randomized, placebo-controlled trial of the antiepileptic drug rufinamide in patients with Lennox–Gastaut syndrome. Eligible patients between 4 and 30 years of age had multiple types of seizures (including tonic–atonic and atypical absence seizures) with a minimum of 90 seizures in the month before baseline and a recent history of a slow spike-and-wave pattern on EEG.

Results: After a 28-day baseline period, 139 eligible patients were randomized; 138 patients received either rufinamide (n = 74) or placebo (n = 64) in addition to their other antiepileptic drugs. The median percentage reduction in total seizure frequency was greater in the rufinamide therapy group than in the placebo group (32.7% vs 11.7%, p = 0.0015). There was a difference (p < 0.0001) in tonic–atonic ("drop attack") seizure frequency with rufinamide (42.5% median percentage reduction) vs placebo (1.4% increase). The rufinamide group had a greater improvement in seizure severity (p = 0.0041) and a higher 50% responder rate compared with placebo for total seizures (p = 0.0045) and tonic–atonic seizures (p = 0.002). The common adverse events (reported by 10% of patients receiving rufinamide) were somnolence (24.3% with rufinamide vs 12.5% with placebo) and vomiting (21.6% vs 6.3%).

Conclusions: Rufinamide was an effective and well-tolerated treatment for seizures associated with Lennox–Gastaut syndrome.