Abstracts

Rationale: Cognitive Impairment is a known risk factor for epilepsy. Many will not respond to the first several antiepilepsy drugs (AEDs). Prior data suggest that after failing 3 AEDs, the chance of becoming seizure-free is extremely low. We report on the efficacy of the newer AEDs in this patient population. Methods: All cognitively impaired (CI) patients with epilepsy that continued to have seizures were available to enter the study. Data was collected between January 1st 1995 and June 30th, 2005. Responses to treatment were recorded for gabapentin (GPN), lamotrigine (LTG), levetiracetam (LEV), oxcarbazepine (OXC), topiramate (TPM), and zonisamide (ZNS). Inclusion criteria included: continued seizures despite trials of at least 4 previous AEDs, age greater than 16, accurate documentation of seizures and adverse events, follow-up of at least 6 months following initiation of each AED exposure (unless AED required stopping for adverse events), and follow-up of at least 12 months to be classified as seizure-free (SF) Results: There were 91 patients that met entry criteria. Five were excluded due to failure to follow study protocol. This left 86 patients for evaluation. Among the 86 patients, a total of 146 drug exposures were recorded. Fifty patients were treated with 1 of the newer AEDs, 21 had trials with 2 newer AEDS, 9 had trials with 3 AEDS, 5 had trials with 4 AEDs, and 1 patient had received 5 of the newer AEDs by the end of the trial. Twenty-one (24.4%) of the CI patients obtained complete seizure control by the end of the trial. One patient became SF on LTG, but was then changed to LEV due to adverse events. The patient remained SF. Thirteen (15.1%) had a 75% reduction (decrease in seizures of at least 75% but <100%) in seizures, 17 (19.8%) had a 50% reduction (decrease in seizures of at least 50% but <75%), 30 (34.9%) had no change and 4 patients had data that was inconclusive. When broken down by drug exposures, 10 patients received trials with GPN, 42 with LTG, 33 with LEV, 9 with OXC, 26 with TPM, and 26 with ZNS. If we look at seizure-freedom from specific AEDs, the results are as follows: 0% of GPN patients became SF, 23.8% of LTG patients, 12.1% of LEV patients, 11.1% of OXC patients, 19.2% of TPM patients, and 7.7% of ZNS patients. Overall discontinuation rates (lack of efficacy, adverse events, other) were 70% for GPN, 9.5% for LTG, 27.3% for LEV, 0% for OXC, 23.1% for TPM, and 50% for ZNS. Conclusions: Despite continuation of seizures after failure of 4 prior AEDs, 24.4% of CI patients became SF (and remained SF for at least 1 year) following treatment with one of the newer AEDs. Another 15.1% had a 75%-99.9% reduction and an additional 19.8% had a 50-74.9% reduction. The highest SF responses were seen with LTG and TPM and no patients treated with GPN became SF, although the number of patients in this subgroup was low.