title: Pregabalin add-on therapy using a flexible, optimized dose schedule in refractory partial epilepsies: a double-blind, randomized, placebo-controlled, multicenter trial.
abstract: OBJECTIVE
  To evaluate the efficacy and safety of pregabalin (PGB) as adjunctive therapy, using a flexible-dosing schedule in Korean patients with refractory partial-onset seizures.
  
  
  METHODS
  This randomized, double-blind (DB), placebo-controlled trial consists of a 6-week baseline, a 12-week DB treatment, and a 1-week taper phase. Patients having recurrent partial seizures (>or=4 seizures during baseline phase) under adequate pharmacotherapy were recruited to be randomized to PGB or placebo (PLC) in a 2 to 1 ratio. Starting dose was 150 mg/day, increased every 2 weeks by 150-mg/day increments up to maximum dose of 600 mg/day. The primary efficacy parameter was response ratio (RRatio) for all partial seizures.
  
  
  RESULTS
  A total of 178 patients (119 in PGB, 59 in PLC) were assigned to the study. Median daily doses of PGB and PLC were 367 and 420 mg/day, respectively. RRatio least squares (LS) mean was -35.8 in the PGB group and -23.2 in the PLC group, with estimated difference in RRatios being -12.6 [95% confidence interval (CI): -22.7 to -2.5, p = 0.015] in the intent-to-treat (ITT) population. Analysis of secondary efficacy measures showed a general trend favoring PGB over PLC. Seventy-seven patients (64.7%) in the PGB group and 18 patients (30.5%) in the PLC group developed adverse events (AEs) related to the study drug. Seven patients (5.9%) in the PGB group discontinued the study prematurely because of AEs. In the post hoc analysis, a significant weight gain (>or=7% of baseline body weight) was found in 24.8% of patients taking PGB, which was more frequent in patients with a lower body mass index (BMI <or=20).
  
  
  CONCLUSIONS
  PGB was effective and easily tolerable as add-on treatment in an Asian population with refractory partial-onset seizures.
authors.affiliation: Department of Neurology, Yonsei University College of Medicine, Severance Hospital, Seoul, Korea. bilee@yuhs.ac
authors.forename: Byung In
authors.initials: BI
authors.lastname: Lee
authors.forename: Sangdoe
authors.initials: S
authors.lastname: Yi
authors.forename: Seung Bong
authors.initials: SB
authors.lastname: Hong
authors.forename: Myeong-Kyu
authors.initials: MK
authors.lastname: Kim
authors.forename: Sang Ahm
authors.initials: SA
authors.lastname: Lee
authors.forename: Sang Kun
authors.initials: SK
authors.lastname: Lee
authors.forename: Dong-Jin
authors.initials: DJ
authors.lastname: Shin
authors.forename: Jae Moon
authors.initials: JM
authors.lastname: Kim
authors.forename: Hong Ki
authors.initials: HK
authors.lastname: Song
authors.forename: Kyoung
authors.initials: K
authors.lastname: Heo
authors.forename: Wing
authors.initials: W
authors.lastname: Lowe
authors.forename: Teresa
authors.initials: T
authors.lastname: Leon
mesh_terms: D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004828:Epilepsies, Partial / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007723:Korea; D008297:Male; D008875:Middle Aged; D017060:Patient Satisfaction; D000069583:Pregabalin; D016896:Treatment Outcome; D055815:Young Adult; D005680:gamma-Aminobutyric Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000927:Anticonvulsants; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid