title: Efficacy and tolerability of topiramate 200 mg/d in the prevention of migraine with/without aura in adults: a randomized, placebo-controlled, double-blind, 12-week pilot study.
abstract: BACKGROUND
  Several large, randomized, double-blind, placebo-controlled trials have found topiramate (TPM) to be effective and generally well tolerated as a preventive therapy for migraine.
  
  
  OBJECTIVE
  This paper evaluates efficacy and safety data from a pilot study of TPM 200 mg/d as preventive therapy in adult subjects with a history of migraine with or without aura.
  
  
  METHODS
  The pilot study had a randomized, double-blind, placebo-controlled design. Subjects were randomized in a 2:1 ratio to receive TPM 200 mg/d or placebo. The double-blind treatment phase consisted of an 8-week titration period (25 mg/d for the first week, followed by weekly increases of 25 mg) and a 12-week maintenance period. The primary efficacy measure was the change in mean monthly migraine frequency. Additional measures were the median percent reduction in monthly migraine frequency and the proportion of responders (those with > or =50%, > or =75%, or 100% reduction in monthly migraine frequency).
  
  
  RESULTS
  The intent-to-treat (ITT) population included 211 subjects (138 TPM, 73 placebo; mean [SD] mean weight, 76.7 [18.7] kg). Of 45 subjects who discontinued the study in the TPM group, 21 discontinued during the titration period, compared with 3 of 13 subjects who discontinued in the placebo group. When the efficacy data were assessed using the per-protocol, analysis-of-covariance model, TPM 200 mg/d was not associated with a significant reduction in mean monthly migraine frequency compared with placebo. A post hoc analysis using a Poisson regression model in the ITT population suggested that TPM significantly reduced mean monthly migraine frequency compared with placebo (P=0.04). A significantly larger proportion of TPM-treated subjects had a > or =75% reduction in monthly migraine frequency compared with placebo (P=0.03). At least 1 adverse event was reported by 90.0% and 69.9% of the TPM and placebo groups, respectively. Treatment-emergent adverse events (AEs) occurring in > or =10% of subjects in the TPM group were paresthesia (45%), dizziness (16%), fatigue (16%), nausea (14%), and weight loss (14%). Most treatment-emergent AEs were rated mild or moderate in severity. Of 3 serious AEs (depression, abdominal pain, leg pain) occurring during the trial, none were considered related to either TPM or placebo.
  
  
  CONCLUSIONS
  In this pilot study, mean monthly migraine frequency did not differ significantly between TPM and placebo.
authors.affiliation: Jefferson Headache Center, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA. stephen.silberstein@jefferson.edu
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Silberstein
authors.forename: Joseph
authors.initials: J
authors.lastname: Hulihan
authors.forename: M Rezaul
authors.initials: MR
authors.lastname: Karim
authors.forename: Shu-Chen
authors.initials: SC
authors.lastname: Wu
authors.forename: Donna
authors.initials: D
authors.lastname: Jordan
authors.forename: Debra
authors.initials: D
authors.lastname: Karvois
authors.forename: Marc
authors.initials: M
authors.lastname: Kamin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000009:adverse effects* / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D005632:Fructose / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D020325:Migraine with Aura / Q000453:epidemiology / Q000517:prevention & control*; D020326:Migraine without Aura / Q000453:epidemiology / Q000517:prevention & control*; D010865:Pilot Projects; D016012:Poisson Distribution; D000077236:Topiramate
chemical_list: D000927:Anticonvulsants; D000077236:Topiramate; D005632:Fructose