The safety and long-term efficacy of zonisamide as adjunctive therapy for focal epilepsy

Abstract

Epilepsy is a chronic disease which affects 1% of the population worldwide. As treatment is required for many years or decades, the long-term efficacy and tolerability of antiepileptic drugs are particularly important. Zonisamide (ZNS) is a second-generation antiepileptic drug with a unique structure and multiple mechanisms of action. Here, recently published long-term outcomes of patient cohorts with focal epilepsy undergoing ZNS treatment are discussed. Whereas ZNS monotherapy maintains similar seizure control efficacy to carbamazepine after 2 years of treatment, seizure-free rates are low in pharmacoresistant patients undergoing late adjunctive therapy. In preselected patient populations derived from double-blind studies, long-term seizure reduction and responder rates support sustained ZNS efficacy, good adherence and long-term retention. Adverse effects include somnolence and weight decrease, but data suggest that long-term treatment with ZNS is safe with only rare newly occurring adverse effects, and good long-term tolerability also regarding mood, behavior, cognition and bone maturation.

Keywords:

• antiepileptic drug
• focal epilepsy
• long-term efficacy
• long-term tolerability
• zonisamide

Financial & competing interests disclosure

A Schulze-Bonhage has provided lectures for Bial, Desitin, EISAI and UCB and has served on advisory boards of EISAI and UCB. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• Zonisamide (ZNS) is a second-generation antiepileptic drug with a wide spectrum of mechanisms reducing abnormal brain hyperexcitability.

• ZNS is approved for the treatment of focal/structural epilepsy in both, children and adults, in monotherapy and combination therapy.

• Long-term studies show an overall good tolerability with no new emerging side effects within a period of 1–6 years.

• Long-term data from children and adolescents suggest safety also regarding hormonal parameters, bone health, cognitive and behavioral development.

• ZNS efficacy is maintained over time without development of tolerance.