title: Could Adult European Pharmacoresistant Epilepsy Patients Be Treated With Higher Doses of Zonisamide?
abstract: OBJECTIVE
  To examine the clinical effect (efficacy and tolerability) of high doses of zonisamide (ZNS) (>500 mg/d) in adult patients with pharmacoresistant epilepsy.
  
  
  METHODS
  Between 2006 and 2013, all epileptic outpatients treated with high doses of ZNS were selected. Safety and efficacy were assessed based on patient and caregiver reports. Serum levels of ZNS and other concomitant antiepileptic drugs were evaluated if available.
  
  
  RESULTS
  Nine patients (5 female): 8 focal/1 generalized pharmacoresistant epilepsy. Mean age: 34 years. Most frequent seizure type: complex partial seizures; other seizure types: generalized tonic-clonic, tonic, myoclonia. Zonisamide in polytherapy in all (100%), administered in tritherapy in 3 (33%) of 9 patients; mean dose: 633 (600-700) mg/d; efficacy (>50% seizure reduction) was observed in 5 (55%) of 9 patients. Five of 9 patients are still taking high doses of ZNS (more than 1 year). Adverse events were observed in 3 (37%) of 8 patients. Good tolerance to high doses of other antiepileptic drugs had been observed in 6 (66%) of 9 patients. Plasma levels of ZNS were only available in 2 patients; both were in the therapeutic range (34.95, 30.91) (10-40 mg/L).
  
  
  CONCLUSIONS
  High doses of ZNS are effective and safe in pharmacoresistant epileptic patients. Therapeutic drug monitoring of ZNS may be considered at therapeutic failure.
authors.affiliation: *Epilepsy Unit, Neurology Service, and †Pharmacology Service, Hospital Universitari de Bellvitge, Barcelona, Spain.
authors.forename: Júlia
authors.initials: J
authors.lastname: Miro
authors.forename: Sònia
authors.initials: S
authors.lastname: Jaraba
authors.forename: Roser
authors.initials: R
authors.lastname: Juvany
authors.forename: Milagrosa
authors.initials: M
authors.lastname: Santurino
authors.forename: Sara
authors.initials: S
authors.lastname: Cobo
authors.forename: Mercè
authors.initials: M
authors.lastname: Falip
mesh_terms: D000328:Adult; D000927:Anticonvulsants / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D000069279:Drug Resistant Epilepsy / Q000188:drug therapy*; D005060:Europe / Q000453:epidemiology; D005260:Female; D006801:Humans; D007555:Isoxazoles / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult; D000078305:Zonisamide
chemical_list: D000927:Anticonvulsants; D007555:Isoxazoles; D000078305:Zonisamide