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NEUROLOGY 2008;70:54-65
© 2008 American Academy of Neurology

Quantifying the response to antiepileptic drugs

Effect of past treatment history

Yitzhak Schiller, MD, PhD and Yussef Najjar, MD

From the Department of Neurology, Rambam Medical Center and the Technion Medical School, Haifa, Israel.

Address correspondence and reprint requests to Dr. Yitzhak Schiller, Department of Neurology, Rambam Medical Center, 1 Efron St., Haifa, Israel 31096

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.

Conclusion: 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.

GLOSSARY: AED = antiepileptic drug; CBZ = carbamazepine; GBP = gabapentin; LTG = lamotrigine; TPM = topiramate; VA = valproic acid.

y_schiller{at}yahoo.com

Disclosure: The authors report no conflicts of interest.

Received November 4, 2006. Accepted in final form June 13, 2007.






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