Abstracts

A previous report (Weatherly et al, 2002) suggested that some epilepsy patients may experience a decline in cognitive functioning when zonisamide (ZNS) is added to the antiepileptic drug (AED) regimen. The current study aims to clarify the association between ZNS and cognitive test performance by comparing neuropsychological test scores of a group of patients who were tested during ZNS therapy to a similar group of patients who were not taking ZNS.
Nineteen intractable epilepsy patients were selected who had undergone neuropsychological testing during ZNS therapy and who were also tested at least once when not on ZNS. Ten patients received baseline testing prior to initiation of ZNS and nine underwent baseline testing a minimum of five days after ZNS had been discontinued. Mean ZNS dose was 355.6 mg (range: 100 [ndash] 700 mg). All patients had a baseline IQ of 70 or greater, had been taking ZNS for at least three days, were not taking topiramate, and were not diagnosed with a progressive neurological disorder. Mean age was 43.1 years, mean education was 12.8 years. Patients were taking an average of 2.17 AEDs at the time of baseline testing. A comparison group was then selected from clinic files that consisted of patients who had undergone neuropsychological testing on two separate occasions at least three days apart. These patients had AED changes that did not include ZNS. The comparison group did not differ from the ZNS group on the variables of age, education, baseline IQ, or number of AEDs at baseline testing. Independent t-tests were conducted to compare the two groups at baseline and second testing on mean neuropsychological test scores measuring working memory, verbal fluency, visual-motor speed, and manual dexterity. Within each group, paired samples t-tests were also conducted to compare baseline performance to mean scores on second testing. Values of p[lt]0.05 were considered statistically significant.
At baseline testing, mean scores on cognitive variables were not statistically different between groups. For the ZNS group, performance was significantly lower on measures of verbal fluency (p[lt]0.01), working memory (p[lt]0.01), and visual-motor speed (p=0.033) compared to baseline. The comparison group did not evidence a statistically significant difference in cognitive test scores between the two testing sessions. Patients on ZNS displayed significantly lower mean cognitive test scores than the comparison group on measures of working memory (p[lt]0.05) and verbal fluency (p[lt]0.01).
These results suggest that ZNS therapy may be associated with a decline in cognitive performance that is not attributable to polypharmacy or medication changes alone. Results also suggest that performance may be more affected on tasks requiring cognitive processing as opposed to psychomotor speed. Additional research is needed to further investigate the possible effects of dose, titration, and duration of ZNS therapy on cognitive test performance.