Abstracts

Rationale: Levetiracetam (LEV) is a second generation AED with indications for the adjunctive treatment of partial onset seizures, JME, and primary generalized tonic-clonic seizures in adults and children with epilepsy. Among adults, initial data have indicated LEV has little adverse cognitive and mood effects. However, relatively little is known about the cognitive and mood effects of AEDs in older adults; despite the recent recognition of the increased prevalence of seizures in the elderly. The observation that older adults are often more sensitive to the adverse effects of AEDs heightens the need to prospectively evaluate the cognitive and mood effects of LEV in older adults. This study evaluated the cognitive and mood effects of LEV in a volunteer sample of healthy community living older adults aged 65-80 years old.Methods: The study used a randomized, double-blind, placebo-controlled, two-period crossover design. To date, 18 older adults (mean age = 72.1 yrs old) completed the study. The sample was predominantly Caucasian (61%) and female (61%). Subjects received either LEV or placebo for 5 wks (2 wks of dose escalation, 2 wks of maintenance therapy, and 1 wk taper). Target maintenance dose was 1,000 mg/day (bid dosing). Evaluations were conducted at Screening, baseline at randomization, end of the First Maintenance Phase, at cross-over, and end of Second Maintenance Phase. Neuropsychological evaluation included 17 measures yielding 41 variables of cognitive function and subjective behavioral effects. Measures included mood assessment (BDI-2, STAI, SEALS, and POMS), and cognitive tests of attention, memory, language, and executive functioning. The study is not completed (Total target N = 20), and rather than breaking blind to the investigators, comparisons were made between all participants on drug versus all participants on placebo phase by a neutral third party. Repeated measures ANOVA was conducted to evaluate for treatment effects.Results: Serum concentrations of LEV demonstrated compliance. No patient had a dementia. No serious adverse events have occurred. With a Bonferroni correction for multiple comparisons, analyses did not reveal significant differences between cognitive measures of attention, memory, language, or executive functioning between the treatment phase and placebo phase. There were trend differences in delayed word list recall (RAVLT) and a measure of speeded reading (p = 0.02). Measures of mood did not significantly differ between phases.Conclusions: LEV had little impact on objective cognitive performance in this sample of older community living adults. This study suggests LEV is not associated with significant adverse cognitive effects in older adults and further supports the use of LEV as an adjunctive medication for treating older adults suffering from epilepsy.