Abstracts

Rationale: Antiepileptic drugs (AEDs), especially first generation AEDs, commonly produce cognitive or mood adverse effects (AEs) associated with impairment of quality of life in individuals with epilepsy. The AED lacosamide (Vimpat®), however, in in the adjunctive treatment randomized double-blind placebo-controlled partial onset seizure trials in adults had low rates of treatment-emergent cognitive/mood AEs. This study further examined cognitive and behavioral outcomes with adjunctive lacosamide therapy using a neuropsychological test battery commonly used in previous AED research and designed to maximize sensitivity to drug effects.Methods: This is a prospective add-on open-label study of 37 patients (14 males, 23 females), age 18-70, with a history of treatment resistant partial epilepsy with a mean seizure frequency of ≥ 2 seizures per month 6 months prior to enrollment. Exclusion criteria included history of drug/alcohol abuse, psychiatric disorder, progressive, demyelinating, or degenerative neurological condition, psychogenic seizures, traumatic brain injury, or cardiac arrhythmia. A comparison of objective and subjective measures was performed pre- and post-treatment with a 6 month interval. These measures included: Beck Depression Inventory-II, Profile of Mood States, QOLIE-89, Controlled Oral Word Association Test, Buschke Selective Reminding Test, Brief Visuo-Spatial Memory Test-Revised, Stroop Color Word Test, Symbol Digit Modalities Test, Digit Span, Digit Cancellation, Connor's Continuous Performance Test, and Trails A and B. Lacosamide was started at 100 mg and could be titrated as needed up to 400 mg. Baseline concomitant AEDs were kept constant.Results: Mean age was 38.3 (18-64 yrs). Two subjects (5%) discontinued. Mean seizure frequency per 28 days decreased significantly (t=4.65, p<.0001) from baseline (7.8 per month) to post-treatment (4.0 per month) with a 50% responder rate of 37% and 11% seizure-free. Composite scores (averaged across variables) were calculated for the cognitive variables, mood/QOL measures (POMS and QOLIE-89), and the BDI-II separately. Differences from pre- to post-treatment were computed used paired samples t-tests. No significant difference was noted on the composite score of the cognitive measures. Likewise, no significant difference was noted on the POMS/QOLIE-89 composite score. However, the BDI-II was significantly lower (t=2.50, p=.018) after treatment (10.0 +-12.3) than before treatment (13.9 +-9.7), and remained significant when the difference score was entered into a regression controlling for demographic and seizure variables.Conclusions: In concordance with previous trials, this small study demonstrated that lacosamide is effective as adjunctive therapy for partial epilepsy, and furthermore may be particularly beneficial for patients with epilepsy regarding better seizure control without significant changes in cognitive functioning, and an improvement in depression. Funding for this study was provided by UCB