DEFINITION — Traditionally, therapeutic failure of three antiepileptic drugs (AEDs) defined intractability [3-11]. With many new AEDs 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 AED 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 AED treatment and followed up to 25 years (median of 7.5 years). 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 [13]. In this cohort, these patterns of AED 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 antiepileptic drugs (whether as monotherapy or in combination) to achieve seizure freedom [12]. They also recommended replacing the term “intractable” with “drug-resistant” epilepsy (DRE).
Some patients who meet this definition of DRE subsequently achieve prolonged (12 months or more) periods of seizure remission [14,15]. However, the risk of seizure relapse in these individuals remains high, greater than 70 percent in one series.
Frequency and severity of seizures are less commonly included in a definition of DRE [4,16]. These can vary among individuals with DRE and are important considerations when weighing treatment options. Similarly, it is important to understand the impact of seizures in the context of the individual's life, job, and other psychosocial circumstances [17]. Even infrequent seizures can have a large impact.
Less often considered, but also important, is the burden of adverse effects of AEDs that a patient experiences. If seizures can be controlled but only at medication doses that produce disabling side effects, then it may also be reasonable to consider that such a person has DRE.