Quantifying the response to antiepileptic drugs: effect of past treatment history.
OBJECTIVE
To quantify the response to treatment with antiepileptic drugs (AEDs) as a function of the past treatment history and identify additional prognostic factors for predicting the response to newly administered AED treatments.


METHODS
A cohort of 478 consecutive patients who received newly administered AED treatments between January 1999 and December 2004 and were followed prospectively for 1.5 to 7.5 years in a single epilepsy clinic.


RESULTS
The response to newly administered AED treatments was highly dependent on the past treatment history. The seizure-free rates decreased from 61.8% for the first AED to 41.7%, 16.6%, and 0% after one, two to five, and six to seven past AEDs proved inefficient. This response curve corresponded to a mono-exponential function with a maximal response of 61.8% and half-decay constant of 1.5 AEDs. Likewise the response curve describing a greater than 50% reduction in seizure frequency corresponded to a mono-exponential function with a maximal response of 85.3% and half-decay constant of two AEDs. Three additional independent prognostic factors for predicting the response to AEDs were identified: type of epilepsy, duration of epilepsy, and number of seizures in the 3 months prior to AED initiation.


CONCLUSIONS
Drug resistance is a graded process that follows a mono-exponential course with a half-decay constant of 1.5 to two antiepileptic drugs (AEDs). Although relative drug-resistant epilepsy can be diagnosed after failure of two past AEDs, absolute drug resistance requires failure of six AEDs, as a significant minority of patients (16.6%) is rendered seizure-free by addition of newly administered AEDs even after failure of two to five past antiepileptic drugs.
Schiller
Yitzhak
Y
Department of Neurology, Rambam Medical Center, 1 Efron St., Haifa, Israel. y_schiller@yahoo.com
Najjar
Yussef
Y
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000927:Anticonvulsants / Q000627:therapeutic use*; D002648:Child; D015331:Cohort Studies; D004334:Drug Administration Schedule; D004827:Epilepsy / Q000188:drug therapy* / Q000453:epidemiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D016896:Treatment Outcome
D000927:Anticonvulsants