Efficacy and safety of adjunctive zonisamide therapy for refractory partial seizures

An approach to the selection of appropriate antiepileptic drugs (AEDs) for inclusion in polytherapy is to take into account both the efficacy of a drug and also its mechanism of action and pharmacokinetic profile. The AED zonisamide is licensed in Europe and the USA for use as adjunctive therapy in adult patients with partial onset epilepsy. Four pivotal clinical studies in patients with refractory partial seizures demonstrated that zonisamide as an add-on was most effective at doses of ≥300 mg/day, with responder rates (≥50% reduction from baseline in seizure frequency) ranging from 28 to 47% for all seizures. In addition, zonisamide has a unique combination of multiple mechanisms of action that are potentially complementary with concomitant AEDs. Zonisamide has no clinically relevant effects on the pharmacokinetics of other commonly used AEDs, however, co-administration with cytochrome P450 3A4 (CYP3A4) inducers or inhibitors may change zonisamide's pharmacokinetic profile. Zonisamide is well tolerated with the majority of adverse events being mild-to-moderate and generally manageable. The tolerability of zonisamide has also been shown to improve with slower drug titration and duration of drug treatment. These characteristics suggest that zonisamide may be suitable as a key adjunct in rational polytherapy.