What is the role of benzodiazepines in the treatment of Lennox-Gastaut syndrome (LGS)?

Updated: Nov 09, 2018
  • Author: Koshi A Cherian, MD; Chief Editor: Amy Kao, MD  more...
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Answer

Clonazepam (Klonopin) is considered an effective first-line AED therapy for seizures associated with LGS. However, the adverse effects and development of tolerance limit its usefulness over time. Dosing on an every-other-day schedule or alternating 2 benzodiazepines daily may slow development of tolerance. The benzodiazepine clobazam, which is widely used as an anticonvulsant in other countries, was approved by the FDA in October 2011. [14] The combination of valproic acid and a benzodiazepine may be better than either drug alone.

In the CONTAIN study of patients with LGS given clobazam, more than 50% of patients had a 50% or greater decrease in weekly drop- and total-seizure frequency. The percentage of patients achieving 100% reduction in drop seizures was 33% for clobazam-treated patients (vs. 7% for placebo) in Quartile 1 (least severe LGS), and 5% of clobazam-treated patients in Quartile 4 (most severe LGS) achieved 100% reduction in drop seizures, versus 0% for placebo. [25]

In a second study (OLE study), through 5 years of clobazam therapy, more than 50% of patients in all 4 quartiles (least severe to most severe LGS) demonstrated a decrease of 50% or more in weekly frequency for drop seizures. More than 12% of patients in Quartile 4 achieved 100% reduction in drop seizures from month 3 through year 5. [25]

The FDA has issued a warning that clobazam, used as add-on therapy to treat seizures in patients with LGS, may trigger Stevens-Johnson syndrome and toxic epidermal necrolysis, rare but potentially fatal cutaneous reactions. [32, 33] The risk of developing these disorders is increased during the first 8 weeks of treatment or when treatment is resumed after it is discontinued. This is not typically seen during clinical practice.


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