Abstracts

Two of the newer anticonvulsants, topiramate (TPM) and zonisamide (ZNS), have a similar chemical structure and mechanism of action. Recent reports (Lee et al, 2003; Weatherly et al, 2003) have also suggested similar cognitive side effect profiles for the two drugs. The current study aims to specifically compare the cognitive side effects of TPM and ZNS. Thirty-eight intractable epilepsy patients were selected retrospectively who had undergone neuropsychological testing during adjunctive therapy with TPM (n = 16) and ZNS (n = 22). All patients had a baseline IQ of 70 or greater, had been taking the respective drugs for at least three days, and did not have a progressive neurological disorder. At baseline, the TPM and ZNS groups were similar in terms of IQ and education, although the TPM group was somewhat younger (mean = 29.0 years vs. ZNS mean = 42.4 years). The mean TPM dose was 234.4 mg/day and the mean ZNS dose was 366.7 mg/day. The cognitive test battery included measures of working memory, verbal fluency, visual-motor speed, and manual dexterity. Paired t-tests were conducted within each group to compare baseline performance to mean scores while on TPM or ZNS therapy. Values of p[lt].05 were considered statistically significant. For the TPM group, significant declines from baseline were observed on measures of animal naming (p [lt] 0.01), phonemic verbal fluency (p = 0.00), digit recall (p = 0.00) and mental sequencing (p [lt] 0.01). For the ZNS group, significant declines were observed on measures of animal naming (p [lt] 0.05), phonemic verbal fluency (p = 0.00), digit recall (p = 0.00), mental sequencing (p [lt] 0.01), and visual-motor speed (p [lt] 0.05). The mean percent change from baseline for each variable was similar between the two groups. However, a greater proportion of the ZNS patients declined one standard deviation or more on measures of visual motor speed and mental sequencing. A greater proportion of TPM patients declined one standard deviation or more on measures of immediate digit recall and animal naming. These results suggest similar cognitive side effect profiles in patients taking TPM and ZNS, with declines noted in both groups on measures of verbal fluency and working memory. The ZNS group also experienced a decline in visual-motor speed. These findings suggest that for both drugs, performance may be more affected on tasks requiring cognitive processing as opposed to motor speed. Patients taking TPM were more likely to decline on measures of digit span and animal naming, while ZNS patients were more likely to decline on measures of mental sequencing and visual motor speed. Additional research is needed to investigate the possible effects of dose, titration, and duration of drug therapy on cognitive test performance.