Impaired verbal fluency under topiramate – evidence for synergistic negative effects of epilepsy, topiramate, and polytherapy



Background and purpose

Treatment with topiramate (TPM) is known to negatively affect executive functions and verbal fluency in particular. However, judgments of cognitive side effects under TPM rarely consider clinical conditions and possible effects of epilepsy, treatment, and drug load.


This retrospective cross-sectional study in large cohorts of patients with epilepsy evaluated the impact of TPM mono- and polytherapy on verbal fluency. To isolate TPM-induced effects from those of epilepsy and antiepileptic medication in general, verbal fluency under TPM (N = 421) was compared to the performance of a matched sample of patients with an antiepileptic medication other than TPM (N = 351), untreated patients (N = 108), and healthy controls (N = 100).


Impaired verbal fluency performance was seen in 77% of the patients treated with TPM. Compared to healthy controls, verbal fluency in untreated patients was reduced by 22%, under monotherapy without TPM by 31% and under TPM monotherapy by 45%. With and without TPM, verbal fluency performance linearly decreased with each additional drug in polytherapy. On each level, performance under TPM was 21–28% worse than in the respective condition without TPM. Unimpaired performance under TPM was primarily associated with lower dose, higher education, and a later onset of epilepsy.


The majority of patients under TPM shows reduced verbal fluency. However, when taking the cumulative negative effects of epilepsy, and the concomitant drug regimen into account, TPM is associated with a 21–28% poorer performance as compared with other drugs. Additionally, the data indicate an impact of dose and reserve capacity on the occurrence of impairments.