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Can drug resistance in epilepsy be minimized? Challenging commonly held beliefs
1Clinical Pharmacology Unit, Department of Internal Medicine and Therapeutics, University of Pavia, Laboratories for Diagnostics and Applied Biological Research, Institute of Neurology, IRCCS C. Mondino Foundation, Pavia, Italy. perucca@unipv.it
Abstract:
Until more efficacious antiepileptic drugs (AEDs) that can tackle the challenge of drug-refractory epilepsy are developed, the best way to minimize inadequate seizure control is to exploit at best available treatments. There are however, discrepancies between commonly held opinions on several aspects of drug therapy, and the body of scientific evidence which exists to support them. This article highlights a few examples, discussing evidence that, contrary to common belief, (i) a significant proportion of patients with newly diagnosed epilepsy respond to concentrations of AEDs below the "therapeutic range" quoted in the literature; (ii) only a small group of patients unresponsive to low to moderate AED dosages become seizure-free after increasing dosage up to the limit of tolerability; (iii) knowledge of mechanisms of AED action can aid in the rational use of AEDs in the clinic; (iv) monitoring serum levels of new generation AEDs can be usefully exploited to improve management, and (v) at least in a subgroup of patients, successful epilepsy surgery cannot be regarded as curative, because seizure control may be dependent upon continuation of AED therapy. It is hoped that increased awareness of these issues could eventually contribute not only to improved clinical outcome, but also to high quality studies in many areas where gaps in knowledge prevent application of truly evidence-based management.
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