Indirect comparison of clobazam and other therapies for Lennox–Gastaut syndrome
Article first published online: 15 FEB 2013
© 2013 John Wiley & Sons A/S
Acta Neurologica Scandinavica
Volume 128, Issue 2, pages 91–99, August 2013
How to Cite
Indirect comparison of clobazam and other therapies for Lennox–Gastaut syndrome. Acta Neurol Scand 2013: 128: 91‒99. © 2013 John Wiley & Sons A/S., , .
- Issue published online: 9 JUL 2013
- Article first published online: 15 FEB 2013
- Manuscript Accepted: 18 DEC 2012
- Lundbeck LLC
- Cohen's d;
- effect size;
- Lennox–Gastaut syndrome;
In the absence of head-to-head trials, it is not feasible to make direct comparisons of antiepileptic therapies for the treatment of Lennox–Gastaut syndrome (LGS). We conducted indirect comparisons of the relative efficacies of clobazam, felbamate, lamotrigine, topiramate, and rufinamide as adjunctive treatments for LGS.
Clinical studies of LGS patients were identified in a 2009 Cochrane review and by electronic database search. Five randomized controlled trials were included in this systematic review, which reports findings from indirect comparisons between clobazam and other approved adjunctive LGS therapies (felbamate, lamotrigine, topiramate, rufinamide) in the United States and Europe. As outcomes were not uniformly reported across studies, the primary efficacy endpoint from each trial was transformed into Cohen's d effect size, to facilitate indirect comparisons. Typical interpretations of Cohen's d results are as follows: d < 0.2, change not detectable; 0.2 ≤ d < 0.5, small change; 0.5 ≤ d < 0.8, moderate change; and 0.8 ≤ d, large change.
High-dosage clobazam (1.0 mg/kg/day) was found to have the strongest treatment effect vs placebo (effect size 0.80), with moderate effects (effect sizes >0.50) for medium-dosage clobazam (0.5 mg/kg/day) and rufinamide. Felbamate, lamotrigine, and topiramate had low effect sizes. Indirect comparisons of numbers of total seizures and tonic–atonic seizures (‘drop attacks’) demonstrated superiority of both clobazam dosages over all comparators.
High- and medium-dosage clobazam was estimated to be more efficacious than other LGS treatments. Our analysis relied on published data and could not draw on direct head-to-head data of clobazam with alternatives. Further comparative research is ongoing to assess the usefulness of clobazam for LGS.