Pharmacoresistant Epilepsy

Pharmacoresistant epilepsy is epilepsy that is uncontrolled (ie, seizures have not decreased or resolved) despite appropriate medical treatment with antiepileptic drugs (AEDs). In a prospective study of 525 patients, ages 9 to 93, Kwan and Brodie investigated how patients with newly diagnosed epilepsy responded to AEDs. More than 30% of patients continue to have seizures in spite of multiple trials with pharmacologic therapy [See figure].1 Seizures may persist in frequency, severity, or duration, or in all 3 aspects. Pharmacoresistant epilepsy also refers to epilepsy that cannot be treated adequately with AEDs because of intolerable side effects or adverse events.

Uncontrolled seizures and intolerable side effects negatively impact quality of life, and numerous sequelae affect the patient. As Brodie and Kwan stated, “Imperfect seizure control can produce disturbed psychosocial integration, which results, for example, in poor academic achievement, diminished self-esteem, dependent behavior, and a restricted lifestyle, all of which lead to an unsatisfactory, downward-spiraling quality of life.” These sequelae make up the “constellation of features” associated with pharmacoresistant epilepsy.

Studies have demonstrated that many patients discontinue AED therapy over time, presumably when AEDs become ineffective, intolerable, or both. Lhatoo et al found the 3-year retention rate to be less than 50% for topiramate and less than 25% for lamotrigine and gabapentin.2 Another study by Krakow et al evaluated continuation rates of levetiracetam, which were shown to decline substantially over time. The estimated continuation rates were 60% at 1 year, 37% at 3 years, and 32% at 5 years.3 Patients who repeatedly discontinue various AED regimens may have pharmacoresistant epilepsy.

.

¹Kwan P, Brodie MJ. N Engl J Med. 2000;342:314-319.
²Lhatoo SD, et al. Epilepsia. 2000;41:1592-1596.
³Krakow K, et al. Neurology. 2001;56:1772-1774.