June 22, 2020

Changes in Cognition After Introduction or Withdrawal of Zonisamide (Zonegran®) Versus Topiramate (Topamax®) in Epilepsy Patients

Abstract, published in Epilepsia

Objective: This study aims to evaluate the impact of zonisamide (ZNS) compared to topiramate (TPM) on cognition in patients with epilepsy. Although the risk of cognitive side effects has been clearly demonstrated for TPM, comparable side effects in ZNS have been suggested but evidence from studies is inconclusive.

Methods: In this retrospective observational study, the team analyzed patients’ records from before and after introduction or withdrawal of ZNS vs TPM. Data were gathered during routine clinical care protocols. Standardized monitoring of executive functions verbal memory and subjective health was performed in 73 patients when TPM (n = 45) or ZNS (n = 28) was introduced and 62 patients when TPM (n = 29) or ZNS (n = 33) was withdrawn.

Results: There was decisive evidence for a negative effect of “add-on” antiseizure therapy with ZNS and TPM on executive function and a positive effect of their withdrawal. The ZNS effect seemed smaller, although the difference was inconclusive. Verbal memory and subjective quality of life were not significantly affected. Subjectively, ZNS was connected to lower anxiety and fewer headaches, whereas TPM had a perceived effect on weight, fluent speech and comprehension, headaches, and balance.

Significance: This is the first study to provide objective evidence for a considerable negative effect of ZNS treatment on executive function. Comparable to the well-known TPM effect, cognition worsens when ZNS is used as add-on therapy and recovers when it is withdrawn. However, most patients do not show a significant negative effect, suggesting disparate susceptibilities to adverse events. The findings emphasize the need for routine monitoring of cognitive side effects to identify early on those patients who are negatively affected by new AED.

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