Abstracts

Rationale: There have been no broad-based studies on AED efficacy in the refractory patient population. We sought to determine whether any AED, in monotherapy or in combination, produced superior efficacy in medically refractory epilepsy by retrospectively analyzing an extensive database of AED therapy of severely developmentally disabled adults with epilepsy. Methods: We obtained records charting monthly seizure frequency and AED treatment for 168 patients at two institutions in Washington State. On the average we analyzed 140 5.8 (mean SEM) months of data for each patient and found the average seizure frequency during each unique AED regimen consisting of 1, 2, or 3 drugs in combination from a list of 8 consisting of (in order of frequency of exposure, and using standard acronyms): LTG, VPA, CBZ, PHT, TPM, LEV, GBP, and ZNS. We then made within-patient comparisons of the ratio of seizure frequencies between different regimens. Results: For patients exposed to both mono- and duotherapy (two drugs at a time), average seizure frequency on duotherapy was 0.81 that of monotherapy, a 19% decrease. However seizure frequency with three drugs at a time was 1.07 times that on duotherapy, demonstrating no benefit of adding a third drug on the average. In comparison of individual AED regimens against a aggregate average of all other regimens to which a patient had been exposed, only the combination of LTG/VPA showed superior efficacy (seizure frequency 0.52 of the average) out of 32 regimens with at least n=5 exposures. In head-to-head comparisons, LTG/VPA was superior to six other regimens, constituting the majority out of 10 statistically significant head-to-head comparisons. The average LTG dose used in monotherapy was 2.9 times that used in combination with VPA, suggesting that serum LTG levels were similar in the two conditions, and that a pharmacokinetic effect of VPA on LTG serum levels did not explain the superiority of the two-drug combination. Conclusions: These results suggest that the combination of LTG/VPA shows superior efficacy in medically refractory epilepsy. Also, while improved efficacy was seen in adding a second AED to prior monotherapy, there was no benefit on the average when adding a third drug. These results may suggest future prospective trials to confirm the superiority of LTG/VPA, and to better understand the underlying mechanisms of its action.