Rufinamide for generalized seizures associated with Lennox-Gastaut syndrome.
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 >or=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.
Glauser
T
T
Comprehensive Epilepsy Center, Division of Neurology, Cincinnati Children's Hospital, 3333 Burnet Avenue, MLC 2015, C-5, Cincinnati, OH 45229, USA. tracy.glauser@cchmc.org
Kluger
G
G
Sachdeo
R
R
Krauss
G
G
Perdomo
C
C
Arroyo
S
S
D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D004827:Epilepsy / Q000188:drug therapy*; D004832:Epilepsy, Absence / Q000188:drug therapy; D004829:Epilepsy, Generalized / Q000188:drug therapy; D004830:Epilepsy, Tonic-Clonic / Q000188:drug therapy; D005260:Female; D006801:Humans; D008297:Male; D013577:Syndrome; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage* / Q000009:adverse effects
D000927:Anticonvulsants; D014230:Triazoles; C079703:rufinamide