A Welcome New Option in Epilepsy Therapy

Andrew N. Wilner, MD


January 05, 2012

Clinical Trials and Clinical Role

The FDA approval of clobazam was based on 2 recent studies.[4,5] In the first study, 68 patients (2-26 years) with Lennox-Gastaut syndrome received open-label low dose (0.25 mg/kg/day) or high dose (1.0 mg/kg/day) clobazam for a 3-week titration, 4-week maintenance, and 3-week taper in addition to their usual treatment.[4] Both doses significantly reduced the frequency of drop attacks, the low dose (P = .01) and the high dose (P < .0001). The high dose also significantly reduced nondrop seizures (P < .0001).

The second study was a phase III, multicenter, randomized, double-blind, placebo-controlled, parallel group trial of 238 patients (aged 2-60 years) with childhood onset of Lennox-Gastaut syndrome.[5] After a 4-week baseline, patients were titrated for 3 weeks, maintained on treatment for 12 weeks (placebo, low dose (0.25 mg/kg/day), medium dose, (0.5 mg/kg/day) or high dose (1.0 mg/kg/day), and then tapered off treatment over 2-3 weeks or entered into the extension phase. The mean percentage decrease in average weekly drop seizures from baseline to the maintenance period was 12.1% for placebo vs 41.2% for low dose (P = .01), 49.4% for medium dose (P = .0015), and 68.3% for high dose (P < .0001), demonstrating increasing efficacy with dose. Decreases in nondrop seizures were not significant. Adverse events that occurred notably more often with clobazam than placebo were somnolence, pyrexia, lethargy, drooling, and constipation.


Clobazam joins 5 other FDA-approved antiepileptic drugs for the treatment of Lennox-Gastaut syndrome: clonazepam, felbamate, lamotrigine, topiramate, and more recently, rufinamide. Valproate is traditionally used as well. However, despite multiple medications and attempts at seizure control with the ketogenic diet, vagus nerve stimulator, and epilepsy surgery, patients rarely become seizure free.[4,6] The long experience of clobazam use outside the United States suggests that this drug harbors no unpleasant surprises regarding safety or side effects. The FDA approval of clobazam represents a valuable additional tool for physicians to decrease drop attacks in their patients with Lennox-Gastaut syndrome. Clobazam is now available at retail pharmacies in the US.


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