OBJECTIVE—To explore the impact of topiramate on tests of intellect and other cognitive processes. METHODS—This was a retrospective study. The neuropsychological test scores of 18 patients obtained before and after the introduction of treatment with topiramate (median dose 300 mg) were compared with changes in test performance of 18 patients who had undergone repeat neuropsychological assessments at the same time intervals. Complaints of cognitive decline precipitated referral for reassessment in five cases in the topiramate treated group. The groups were matched for age and intellectual level at the time of the first assessment. Patients were assessed using the WAIS-R, tests of verbal and non-verbal memory, language, and perceptual processing. A subgroup of patients underwent a brief reassessment after the withdrawal or substantial reduction of topiramate. RESULTS—Repeat assessments in those taking topiramate were associated with a significant deterioration in many domains, which were not seen in the comparison group. The greatest changes were for verbal IQ, verbal fluency, and verbal learning (p<0.001). Improvements in verbal fluency(p<0.05), verbal learning (p<0.01), and digit span (p<0.001) wererecorded in those patients who had topiramate withdrawn or reduced. CONCLUSIONS—In ourpatient group topiramate had a negative impact on cognition which wasconsistent with subjective complaints of patients. Tests requiringverbal processing seemed especially sensitive to the drug. A decline inverbal intellect (VIQ), a measure which has been considered by some tobe insensitive to antiepileptic drug effects, was particularlystriking. Caution is warranted in the interpretation of the findingsdue to methodological limitations of the study design. Furtherinvestigation of mediating factors such as serum concentrations,comedication, and other potential risk factors, however, is needed toenable appropriate targeting of treatment with this effectiveantiepileptic agent.
