Epileptic Disorders - Editor's Choice
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Franck Semah, Pierre Thomas, Safia Coulbaut, Philippe Derambure
Commentary by Graeme J Sills PhD,
Epileptic Disorders Associate Editor
There are many significant questions in epilepsy therapeutics that remain to be answered, not least of which is what to do after the first drug fails. Much has been written on this issue but relatively few investigators have been brave enough to tackle it in a prospective manner. In this issue, Semah and colleagues report the outcome of a 10-year odyssey to shed light on whether it is better to switch or to add after the first medication has proved ineffective. In doing so, they also highlight the many challenges associated with these types of investigations.
In some ways, the results are the least interesting aspect of this article. In patients with recently diagnosed focal epilepsy who have failed their first choice antiepileptic drug due to incomplete seizure control at an adequate dose, there is no apparent difference between switching to another appropriate monotherapy and adding-in a second drug, in terms of either efficacy or tolerability. This is perhaps unsurprising given the size of the study population, their expected pharmacological responsiveness, and what we know from previous work.
Instead, it is the extreme heterogeneity, in both patient characteristics and drug choice, that sparks the greatest interest in this report and which serves as a reminder of the difficulty in delivering a study that is reflective of real-world clinical practice but also scientifically and statistically robust. This article is far from definitive in terms of treatment policy after initial drug failure in epilepsy but the authors should be applauded for their initial ambition, their continuing perseverance and their eventual honesty. There is a salutary lesson here for anyone who dreams of tackling the big issues in the pharmacological management of epilepsy.