title: Zonisamide improves wearing-off in Parkinson's disease: A randomized, double-blind study.
abstract: BACKGROUND
  Previously, we reported 50 mg/d zonisamide improved wearing-off without increasing dyskinesia in patients with Parkinson's disease (PD).
  
  
  METHODS
  To determine the efficacy of zonisamide for treatment of "off" time in PD patients, we conducted a multicenter, randomized, double-blind, parallel-group, placebo-controlled study in Japan. Patients with PD and wearing-off received placebo for 4 weeks and then were treated for 12 weeks with zonisamide 25 or 50 mg/d or placebo, in addition to their previous therapy. The primary endpoint was the change from baseline in daily "off" time as determined by patients' diaries at the final assessment. Secondary endpoints included changes from baseline in the total scores of the Unified Parkinson's Disease Rating Scale Parts I, II, III, and IV, the dyskinesia duration, and PDQ-39 score.
  
  
  RESULTS
  Of 422 patients enrolled, 389 (131 for placebo, 130 for zonisamide 25 mg, and 128 for zonisamide 50 mg) were randomized, and 354 (120, 119, and 115, respectively) completed the study. The "off" time significantly reduced by 0.719 ± 0.179 h for zonisamide, 50 mg compared with placebo (0.011 ± 0.173 h, P = 0.005). Although the incidence of somnolence was higher for zonisamide (3.1% for zonisamide 25 mg, 6.3% for zonisamide 50 mg) than for placebo (2.3%), the incidences of the other adverse events, including dyskinesia or hallucination, for both zonisamide treatments were comparable to those for placebo.
  
  
  CONCLUSIONS
  The study provides evidence that confirms the efficacy of zonisamide 50 mg/d for reduction in "off" time in PD patients with wearing-off phenomena.
authors.affiliation: Department of Neurology, National Center Hospital, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Murata
authors.affiliation: Department of Neurology, Sagamihara National Hospital, Kanagawa, Japan.
authors.forename: Kazuko
authors.initials: K
authors.lastname: Hasegawa
authors.affiliation: International University of Health and Welfare Graduate School, Tokyo, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kanazawa
authors.affiliation: Sumitomo Dainippon Pharma Co., Ltd, Tokyo, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Fukasaka
authors.affiliation: Sumitomo Dainippon Pharma Co., Ltd, Tokyo, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kochi
authors.affiliation: Sumitomo Dainippon Pharma Co., Ltd, Tokyo, Japan.
authors.forename: Rieko
authors.initials: R
authors.lastname: Shimazu
mesh_terms: D000368:Aged; D000927:Anticonvulsants / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D015259:Dopamine Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007555:Isoxazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D007564:Japan; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000188:drug therapy*; D016896:Treatment Outcome; D000078305:Zonisamide
chemical_list: D000927:Anticonvulsants; D015259:Dopamine Agents; D007555:Isoxazoles; D000078305:Zonisamide
keywords: Parkinson's disease; levodopa; randomized controlled trial; wearing-off; zonisamide