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A consensus is being reached that, for operational purposes, pharmacoresistance can be suspected when two appropriately chosen, well-tolerated, first-line antiepileptic drugs (AEDs) or one monotherapy and one combination regimen have failed due to lack of efficacy. Poor prognostic factors include lack of response to the first AED, specific syndromes, symptomatic etiology, family history of epilepsy, psychiatric comorbidity, and high frequency of seizures. These observations suggest that prognosis can often be determined early in the course of the disorder. We propose a management paradigm that aims to maximize the chance of successful AED therapy, including the early use of \u201crational polytherapy\u201d for patients not responding to monotherapy, and to identify efficiently patients suitable for \u201ccurative\u201d resective surgery, in particular those with mesial temporal lobe epilepsy. An orderly approach to each epilepsy syndrome will optimize the chance of perfect seizure control and help more patients achieve a fulfilling life.<\/jats:p>","DOI":"10.1017\/s1092852900008476","type":"journal-article","created":{"date-parts":[[2015,12,8]],"date-time":"2015-12-08T17:11:24Z","timestamp":1449594684000},"page":"110-119","source":"Crossref","is-referenced-by-count":77,"title":["Drug Treatment of Epilepsy: When Does It Fail and How to Optimize Its Use?"],"prefix":"10.1017","volume":"9","author":[{"given":"Patrick","family":"Kwan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin 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