Pharmacoresistant Epilpesy

Pharmacoresistant epilepsy is epilepsy that is uncontrolled (i.e. seizures have not decreased or resolved) despite appropriate medical treatment with antiepileptic drugs (AEDs). More than 30% of patients continue to have seizures in spite of multiple adequate trials with pharmacologic therapy.¹ Seizures may persist in terms of 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. These, too, negatively impact quality of life. The dilemma is in determining the point at which epilepsy is considered pharmacoresistant. With the many AEDs now available, the question is how many - alone or in combination - to try before turning to nonpharmacologic options. Brodie and Kwan suggest a staged approach to epilepsy therapy that includes considering nonpharmacologic options after the failure of 2 to 3 well-tolerated AEDs to produce adequate seizure control.²

Certain risk factors may help physicians identify patients with pharmacoresistant epilepsy early so that additional or alternative interventions (e.g. ketogenic diet, intracranial epilepsy surgery or VNS Therapy) can be used to avoid the long-term consequences of uncontrolled seizures.
 

1. Limited success with any other single AED or combination of AEDs¹
2. Inadequate response to first AED trial¹
3. Predictors related to intolerable side effects¹
4. Frequent seizures before initial therapy¹
5. Early age at onset³
6. Cause or origin of seizures¹
7. Electroencephalographic (EEG) factors³
8. Imaging with positron emission tomography (PET)⁴

¹Kwan P, Brodie MJ. N.Engl.J.Med. 2000; 342:314-319.
²Brodie MJ, Kwan P. Neurology. 2002; 58 (suppl.5):S2-S8.
³Ko TS, Holmes GL. Clin.Neurophysiol. 1999; 110:1245-1251.
⁴Dupont S et al. Arch.Neurol. 2000; 57:1331-1336.
 

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