Abstracts

RATIONALE: Adverse effects of Topiramate are described as predominantly related to frontal lobe function, development of side effects appears to be based on an idiosyncratic susceptibility for the agent rather than to be dose-dependent.
Topiramate (TPM) is a highly effective drug used in the treatment of partial onset epilepsy with or without secondary generalization. TPM can produce considerable cognitive side effects such as psychomotor slowing, impaired memory function, speech-related problems and further cognitive complaints. It has been argued, that most of these effects develop during titration periods (generally within the first 2 months of treatment) as a result of high initial doses or rapid dose escalation and that problems resolve when patients become habituated to the agent or dosage is adjusted. In this study we investigated the effects of TPM on cognitive performance in patients with epilepsy, who had been receiving TPM for more than two months in relation to current blood serum levels and daily dosages of TPM.
METHODS: This was a retrospective study. The neuropsychological test scores of a sample of 64 patients on TPM were compared to those of a group of 86 patients on Lamotrigine (LTG) as corresponding agent (control). Groups did not differ with regard to gender, age, IQ, number of adjunctive antiepileptic drugs, onset and duration of epilepsy or localization and lateralization of epileptic focus. All patients had undergone neuropsychological assessment of language abilities, motor function, attention, verbal and non-verbal memory.
RESULTS: The TPM-group performed significantly poorer on verbal fluency (p[lt]0.001), measures of working memory (p=0.001), and verbal and non-verbal recognition memory (p[lt]0.01) as compared to the LTG-group (MANOVAs). Neither language function per se, nor general memory capacity or attention turned out to be selectively affected by TPM. Within the TPM-group, none of the tested parameters was correlated to current blood serum levels or daily dosages of TPM.
CONCLUSIONS: According to present data, TPM appears to exert negative influence particularly on measures of working memory indicating frontal lobe dysfunction. Since these results were obtained beyond titration periods, it can be assumed that cognitive side effects due to TPM tend to persist. Obviously many patients do not habituate to this agent and may develop adverse effects already at low dosages. These findings are of special importance for test results of patients with epilepsy undergoing pre-surgical neuropsychological assessment for the purpose of evaluation of seizure focus lateralization or localization. The test results of patients on TPM have to be considered with special care in order not to overestimate frontal lobe dysfunction.