Zonisamide in the treatment of epilepsy

Expert Opin Pharmacother. 2011 Nov;12(16):2573-81. doi: 10.1517/14656566.2011.622268. Epub 2011 Oct 4.


Introduction: Epilepsy affects approximately 3 million people in the USA and up to 2% of the worldwide population. The yearly direct medical cost of epilepsy in the USA alone is estimated to be $9.5 billion. Epilepsy affects both children and adults and can significantly impair quality of life. Zonisamide is a second-generation antiepileptic drug (AED) that has broad-spectrum efficacy, a favorable side-effect profile and simpler dosing than earlier drugs.

Areas covered: The history of the development of zonisamide is reviewed in this paper. The data available demonstrating zonisamide's mechanism of action as a voltage-gated sodium channel inhibitor, a T-type calcium channel inhibitor, an enhancer of GABA release and an inhibitor of glutamate release are also reviewed. Four key Phase III clinical trials are reviewed in detail, as are subsequent postmarketing trials that have expanded the therapeutic indication for zonisamide.

Expert opinion: From the available clinical data, zonisamide is a viable first-line and adjunctive therapeutic for partial-onset epilepsy and should be considered as an adjunctive therapeutic for a wide-range of generalized epilepsies.

Publication types

  • Review

MeSH terms

  • Animals
  • Anticonvulsants / pharmacokinetics
  • Anticonvulsants / pharmacology
  • Anticonvulsants / therapeutic use*
  • Calcium Channel Blockers / pharmacokinetics
  • Calcium Channel Blockers / pharmacology
  • Calcium Channel Blockers / therapeutic use
  • Calcium Channels, T-Type / metabolism
  • Epilepsy / drug therapy*
  • Epilepsy / metabolism
  • Humans
  • Isoxazoles / pharmacokinetics
  • Isoxazoles / pharmacology
  • Isoxazoles / therapeutic use*
  • Sodium Channel Blockers / pharmacokinetics
  • Sodium Channel Blockers / pharmacology
  • Sodium Channel Blockers / therapeutic use
  • Zonisamide


  • Anticonvulsants
  • Calcium Channel Blockers
  • Calcium Channels, T-Type
  • Isoxazoles
  • Sodium Channel Blockers
  • Zonisamide