title: Comparative trial of low- and high-dose zonisamide as monotherapy for childhood epilepsy.
abstract: OBJECTIVE
  To evaluate the effectiveness of zonisamide (ZNS) as monotherapy in children with newly diagnosed epilepsy.
  
  
  METHODS
  This randomized, multicenter trial included a 2-4-week titration and a 24-week maintenance phase after randomization to low-(3-4 mg/kg/day) or high-(6-8 mg/kg/day) dose groups as target maintenance dosages. The primary outcome measure was the seizure-free rate over 6 months, while a secondary measure was the change in cognition and behavior from screening to the end of the maintenance phase.
  
  
  RESULTS
  Out of 125 patients enrolled, 90 (49 low-dose and 41 high-dose) completed the study. Forty-one patients (63.1%) in the low-dose group and 34(57.6%) in the high-dose group achieved 6 months' freedom from seizures (p=0.66). After treatment, the picture arrangement subtest improved in the low-dose group (p=0.047) while the vocabulary subtest worsened in the high-dose group (p=0.020). Comparing between the two groups, the vocabulary subtest in the high-dose group was significantly worse than that in the low-dose group (p=0.002). Social competence, somatic complaints, depression/anxiety and delinquent and aggressive behavior in the low-dose group were significantly improved (p<0.05). Moreover, total social competence, somatic complaints, delinquent behavior, externalizing, and total behavior problems were significantly more improved in the low-dose group than the high-dose group (p<0.05).
  
  
  CONCLUSIONS
  ZNS is an effective monotherapy for newly diagnosed childhood epilepsy. Lower doses of ZNS have a similar efficacy and more beneficial neurocognitive effects compared to higher doses. When prescribing higher doses of ZNS, one must be aware of the possible manifestation of problems associated with language development, such as those affecting vocabulary acquisition.
authors.affiliation: Department of Pediatrics, Korea University College of Medicine, Republic of Korea.
authors.forename: So-Hee
authors.initials: SH
authors.lastname: Eun
authors.forename: Heung Dong
authors.initials: HD
authors.lastname: Kim
authors.forename: Baik-Lin
authors.initials: BL
authors.lastname: Eun
authors.forename: In Kyu
authors.initials: IK
authors.lastname: Lee
authors.forename: Hee Jung
authors.initials: HJ
authors.lastname: Chung
authors.forename: Joon Sik
authors.initials: JS
authors.lastname: Kim
authors.forename: Hoon-Chul
authors.initials: HC
authors.lastname: Kang
authors.forename: Young-Mock
authors.initials: YM
authors.lastname: Lee
authors.forename: Eun Sook
authors.initials: ES
authors.lastname: Suh
authors.forename: Dong Wook
authors.initials: DW
authors.lastname: Kim
authors.forename: Soyong
authors.initials: S
authors.lastname: Eom
authors.forename: Joon Soo
authors.initials: JS
authors.lastname: Lee
authors.forename: Han Ku
authors.initials: HK
authors.lastname: Moon
mesh_terms: D000293:Adolescent; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004827:Epilepsy / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007555:Isoxazoles / Q000008:administration & dosage* / Q000627:therapeutic use; D008297:Male; D016896:Treatment Outcome; D000078305:Zonisamide
chemical_list: D000927:Anticonvulsants; D007555:Isoxazoles; D000078305:Zonisamide