Abstracts

Both lamotrigine (LAMICTAL^[reg], LTG) and topiramate (TPM) are used as adjunctive therapy for refractory partial seizure disorders in adults. For many patients, anticonvulsant-related disturbances of cognitive function rank as important concerns and major determinants of quality-of-life. Data from clinical trials of TPM in people with epilepsy suggest a substantial risk of cognitive impairment, whereas data from similar LTG trials suggest a low incidence of such side effects. However, direct comparison between the two agents cannot be definitively made because of differences in trial design and study populations. The clinical trial reported here was a randomized, double-blind comparison of the cognitive effects of LTG and TPM as adjunctive therapy in adult patients with partial seizures. Eligible patients had a diagnosis of partial epilepsy and were inadequately controlled by a regimen containing carbamazepine (CBZ) or phenytoin (PHT). There were three study phases: Baseline; Escalation (8 weeks) to 500mg/day LTG or 300mg/day TPM; Maintenance (8 weeks). The dose of TPM and duration of escalation were designed to minimize the cognitive impact of TPM. Patients were administered a battery of six cognitive tests at screen, end of Escalation Phase, and at the end of the Maintenance Phase. The primary endpoint was the change from Baseline to end of Maintenance Phase on a combined analysis of these standardized measures of cognition using an O[apos]Brien test and analysis of variance methods testing the overall sum of the ranks of the six cognitive tests. 192 patients (96 LTG, 96 TPM) were randomized and received study drug. The mean age was 39.2 years in the LTG group and 40.5 years in the TPM group. The change from Baseline on the combined analysis of the standardized measures of cognition (primary endpoint) to the end of the Maintenance Phase showed a significant advantage (p[lt]0.001) for LTG. For three of the six tests, there was a statistically significant difference in favor of LTG for the Controlled Oral Word Association Test (COWA) (p[lt]0.001), Stroop Test (p=0.038), and the Symbol-Digit Modalities Test (p[lt]0.001). The most common [ge]10%) treatment-emergent adverse events (AEs) were headache (13% LTG, 24% TPM), dizziness (19% LTG, 9% TPM), nausea (11% LTG, 6% TPM), and fatigue (8% LTG, 13% TPM). The percent of patients from each treatment group who discontinued due to an AE was 21% in the LTG group and 25% in the TPM group. More patients in the TPM group prematurely discontinued due to cognitive decline (15% TPM, 0% LTG). Unlike LTG, adjunctive therapy with TPM had a negative impact on cognition in patients with refractory partial epilepsy. (Supported by GlaxoSmithKline Research and Development.)