Long-term effects of zonisamide in adult patients with intellectual disability

This study aimed to evaluate the tolerability and efficacy of zonisamide (ZNS) in adult patients with drug-resistant epilepsy and intellectual disability (ID) at our epilepsy centre.

By conducting a monocentric, open-label observational study based on standardized seizure records we retrospectively assessed 87 patients (39 female, mean age 40.6 ± 13.6, range 18-75 years) with ID and drug-resistant epilepsy. Evaluation, including calculation of retention rate, was performed for the intervals 3-6, 9-12 and 21-24 months after ZNS initiation. The Clinical Global Impressions Scale-Improvement (CGI-I) was used to detect qualitative changes in seizure severity and clinical status. Via regression analysis and the generalized estimating equations approach, we examined changes in body weight and impact of patient age also considering associations with other patient characteristics.

The retention rate after 24 months was 60%. 28% discontinued ZNS therapy due to increasing seizure frequency, lack of efficacy or adverse events (AEs). Sedation (38%), language impairment (19%), challenging behaviour (10%), mild rash (10%) and dizziness (10%) were the commonest AEs. The responder rate was 40%, eight patients (9%) became seizure free. We found CGI-I to be dose-dependent. Regarding changes in body weight, we observed no difference between patients continuing or withdrawing ZNS therapy and responders or non-responders. Though, we identified older age as a significant risk factor for weight loss.

Zonisamide may provide a safe and efficient therapeutic option for patients with ID and drug-resistant epilepsy. However, weight status should be carefully monitored, especially in elderly patients.