Abstracts

This study examined individual variability of the neuropsychological effects of lamotrigine (LTG) and topiramate (TPM) in healthy adults. We have previously reported that TPM produces significantly more adverse neuropsychological effects than LTG in healthy adults. Here, we examined the magnitude of effects and the variability across subjects to determine if certain individuals were more susceptible to the adverse neuropsychological effects. This was a randomized, double-blind, two-period crossover study of 47 healthy adults (19 men and 28 women; mean age = 37 years) who completed both phases of the study. Each drug was given for 12 weeks (7 weeks dose escalation followed by 4 weeks maintenance, and then 1 week taper). Initial dose was 25mg/day, and target maintenance dose was 300mg/day for both drugs. Neuropsychological evaluations were conducted at Screening, end of First and Second Maintenance Phase, and Post-treatment Period. There were 41 variables across 17 measures: Selective Reminding Test, MCG Paragraph Memory, Boston Naming, Animal Naming, Controlled Oral Word Association, Stroop, Symbol Digit Modalities Test, Digit Cancellation, Grooved Pegboard, Choice Reaction Time, Visual Serial Addition Test, Continuous Performance Task, A-B Neurotox, SEALS, POMS, SF-12, and QOLIE-89 attention, language and memory subscales. Difference scores were calculated for each drug compared to the non-drug conditions. The number of variables with difference scores were determined for each subject across the following standard deviation (SD) ranges: [le] -2; [le] -1; [ge]+1; [ge]+2. 12 subjects on TPM had [gt]25% of their variables reduced [ge] -2 SD compared to the non-drug condition, all 41 had [gt]25% variables reduced [ge] [ndash]1 SD, and 12 had [gt]50% reduced [ge] [ndash]1 SD. For LTG, 2 subjects had [gt]25% variables reduced [ge] [ndash]2 SD, 6 had [gt]25% variables reduced [ge] [ndash]1 SD, and none had [gt]50% reduced [ge] [ndash]1 SD. 18 subjects on LTG had [gt]25% of their variables increased [ge] +1 SD, and none for TPM. No subject on either drug had [gt]25% of their variables increased [ge] +2 SD. Lamotrigine produced fewer neuropsychological adverse effects than topiramate in monotherapy at the dosages, titrations and timeframes employed in this study. Variability of drug effects was seen across subjects. Certain individuals appear to be particularly sensitive to adverse cognitive effects. In clinical practice, recognition of patients who are similarly hypersensitive to the adverse cognitive effects of antiepileptic drugs is important. (Supported by Glaxo SmithKline)