title: Pregabalin versus pramipexole: effects on sleep disturbance in restless legs syndrome.
abstract: OBJECTIVE
  To compare pregabalin versus placebo and pramipexole for reducing restless legs syndrome (RLS)-related sleep disturbance.
  
  
  METHODS
  Randomized, double-blinded, crossover trial.
  
  
  METHODS
  Twenty-three US sleep centers.
  
  
  METHODS
  Eighty-five individuals with moderate to severe idiopathic RLS and associated sleep disturbance.
  
  
  METHODS
  Participants were randomized across 6 treatment sequences comprising three 4-week periods on pregabalin 300 mg/day (n = 75), pramipexole 0.5 mg/day (n = 76), or placebo (n = 73).
  
  
  RESULTS
  Polysomnography was conducted over 2 nights at the end of each period. Primary (wake after sleep onset [WASO], pregabalin vs placebo) and key secondary endpoints were analyzed for statistical significance, with descriptive statistics for other endpoints. Pregabalin improved sleep maintenance, demonstrated by reductions in WASO (-27.1 min vs placebo [P < 0.0001]; -26.9 vs pramipexole) and number of awakenings after sleep onset (-2.7 vs placebo; -7.9 vs pramipexole [P < 0.0001]) by polysomnography, and an increase in subjective total sleep time (30.8 min vs placebo [P < 0.0001]; 26.8 vs pramipexole). Pregabalin also increased slow wave sleep duration (20.9 min vs placebo; 32.1 vs pramipexole [P < 0.0001]). Reduction in periodic limb movement arousal index (PLMAI) with pregabalin was similar to pramipexole and greater than placebo (-3.7 PLMA/h [P < 0.0001]), although reduction in total PLM in sleep was less than for pramipexole.
  
  
  CONCLUSIONS
  This study demonstrated improvements in objective and subjective measures of sleep maintenance and sleep architecture with pregabalin compared with placebo and pramipexole. Effects of pregabalin on periodic limb movement arousal index were comparable to pramipexole.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier, NCT00991276; http://clinicaltrials.gov/show/NCT00991276.
authors.affiliation: Sleep Research Institute, Madrid, Spain.
authors.forename: Diego
authors.initials: D
authors.lastname: Garcia-Borreguero
authors.affiliation: Pfizer Global Research and Development, Groton, CT.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Patrick
authors.affiliation: Pfizer Global Research and Development, Groton, CT.
authors.forename: Sarah
authors.initials: S
authors.lastname: DuBrava
authors.affiliation: University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: Philip M
authors.initials: PM
authors.lastname: Becker
authors.affiliation: Sleep Disorders Center of Georgia, Atlanta, GA.
authors.forename: Alan
authors.initials: A
authors.lastname: Lankford
authors.affiliation: Pfizer Global Research and Development, Groton, CT.
authors.forename: Crystal
authors.initials: C
authors.lastname: Chen
authors.affiliation: Pfizer Global Research and Development, Groton, CT.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Miceli
authors.affiliation: Pfizer Global Research and Development, Groton, CT.
authors.forename: Lloyd
authors.initials: L
authors.lastname: Knapp
authors.affiliation: Johns Hopkins University, Department of Neurology, Baltimore, MD.
authors.forename: Richard P
authors.initials: RP
authors.lastname: Allen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001143:Arousal / Q000187:drug effects; D052160:Benzothiazoles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D018592:Cross-Over Studies; D018491:Dopamine Agonists / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009068:Movement / Q000187:drug effects; D017286:Polysomnography; D000077487:Pramipexole; D000069583:Pregabalin; D012148:Restless Legs Syndrome / Q000150:complications* / Q000188:drug therapy / Q000503:physiopathology; D012890:Sleep / Q000187:drug effects; D012893:Sleep Wake Disorders / Q000150:complications* / Q000188:drug therapy* / Q000503:physiopathology; D055815:Young Adult; D005680:gamma-Aminobutyric Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D052160:Benzothiazoles; D018491:Dopamine Agonists; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid; D000077487:Pramipexole
keywords: Restless legs syndrome; clinical trial; polysomnography; sleep