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Evaluation and management of drug-resistant epilepsy

Joseph I Sirven, MD
Section Editor
Paul Garcia, MD
Deputy Editor
April F Eichler, MD, MPH


Patients with epilepsy whose seizures do not successfully respond to antiseizure drug therapy are considered to have drug-resistant epilepsy (DRE). This condition is also referred to as intractable, medically refractory, or pharmacoresistant epilepsy. As many as 20 to 40 percent of patients with epilepsy (roughly 400,000 people living in the US) are likely to have refractory epilepsy. The annual cost for patients with epilepsy in the United States is estimated to be approximately 12.5 billion dollars (based on a 1995 survey); DRE contributes a substantive proportion of this cost [1,2]. People with DRE have the greatest burden of epilepsy-related disabilities, further contributing to the scope of this problem.

Because of the need to individualize therapy, no rigid set of guidelines can be applied to determine medical intractability, however, population-based studies have provided information regarding the prognosis of DRE that are helpful in making treatment decisions. Resective surgical therapy for epilepsy has the potential to eliminate seizures in many patients with localization-related DRE.

This topic discusses the evaluation and approach to the management of individuals with DRE. Other issues regarding the evaluation and treatment of individuals with seizures and epilepsy are presented separately. (See "Overview of the management of epilepsy in adults" and "Evaluation of the first seizure in adults" and "Initial treatment of epilepsy in adults" and "Surgical treatment of epilepsy in adults" and "Vagus nerve stimulation therapy for the treatment of epilepsy".)


Traditionally, therapeutic failure of three antiseizure drugs defined intractability [3-11]. With many new antiseizure drugs available in recent years, it might have been expected that more, rather than fewer, drug trials would be recommended before determining intractability. However, several prospective case series have shown that a high likelihood of medical intractability can be identified after two unsuccessful trials, as with each antiseizure drug failure, the likelihood of successful treatment with other drugs diminishes [5-13]. As an example, in one study, 1098 adolescent and adult patients with a diagnosis of epilepsy were started de novo on antiseizure drug treatment and followed up to 25 years (median of 7.5 years) [13]. With the first drug trial, 49 percent became seizure-free. A second medication trial produced remission in an additional 13 percent, while only a further 4 percent became seizure-free on a third medication regimen. In this cohort, these patterns of antiseizure drug responsiveness largely persisted over time.

A task force of the International League against Epilepsy proposed that drug-resistant be defined as the failure of adequate trials of two tolerated, appropriately chosen and administered antiseizure drugs (whether as monotherapy or in combination) to achieve seizure freedom [12]. They also recommended replacing the term "intractable" with "drug-resistant" epilepsy (DRE).


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Literature review current through: Sep 2016. | This topic last updated: Sep 9, 2016.
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