Abstracts

Cognitive side effects of antiepileptic drugs (AEDs) can have a negative impact on a patient[apos]s quality of life. Several new AEDs have been introduced in the last decade, but their relative effects on cognition are uncertain. The primary objective of this study was to compare the effects of lamotrigine and topiramate on neuropsychological function. Healthy volunteers were studied to avoid confounding effects of seizures, to facilitate a crossover design with direct drug comparisons, and to allow generalization to other patient groups treated with AEDs.
This is an interim analysis of an ongoing randomized, double-blind, double-dummy, two-period crossover study comparing the effects of lamotrigine and topiramate on neuropsychological function in healthy adults. Subjects were randomized (1:1) in the first treatment period to receive either lamotrigine or topiramate for 12 weeks (7 weeks of dose escalation followed by 4 weeks of maintenance therapy and then 1 week of tapering off study drug). The target maintenance doses for both lamotrigine and topiramate was 300mg/day; subjects had to reach a minimum dose of 200mg for each drug by Week 8. After completion of the first treatment period, subjects entered a 4 week washout. Subjects then received the alternate therapy for 12 weeks in the second treatment period with the same dosing format. Neuropsychological evaluation included 16 measures yielding 31 variables of cognitive function and subjective behavioral effects. The measures included: Selective Reminding Test, MCG Paragraph Memory, Boston Naming Test, Animal Naming, Controlled Oral Word Association, Stroop Test, Symbol Digit Modalities Test, Digit Cancellation, Grooved Pegboard, Choice Reaction Time, Visual Serial Addition Test, Continuous Performance Task, A-B Neurotoxicity Scale, QOLIE-89 Attention, Language and Memory subscales, SEALS inventory, and Profile of Mood States. Evaluations were conducted at Screening, at the end of the first Maintenance Phase, at the end of the second Maintenance Phase, and in the Post-treatment Period.
Direct comparisons of the two drug conditions using t tests are presented here for 26 subjects who have completed the study to date. Significant differences were present for 23 of the 31 variables, all in favor of lamotrigine. Significant differences were seen for Selective Reminding Test; MCG Paragraph Memory; Boston Naming Test; Animal Naming; Controlled Oral Word Association; Stroop Test (Word and Color Naming); Symbol Digit Modalities Test; Choice Reaction Time; Visual Serial Addition Test; Continuous Performance Task; A-B Neurotoxicity Scale; all 3 cognitive subscales for QOLIE-89; 4/5 SEALS factors; and Vigor and Confusion scales from Profile of Mood States.
At the dosages and escalation rates used in this study, lamotrigine produced fewer cognitive and subjective side effects than topiramate.
[Supported by: Glaxo SmithKline]