title: Tiagabine increases slow-wave sleep in a dose-dependent fashion without affecting traditional efficacy measures in adults with primary insomnia.
abstract: BACKGROUND
  This study evaluated dose-response effects of tiagabine on sleep in adults with primary insomnia.
  
  
  METHODS
  Men and women with primary insomnia (DSM-IV-TR) were randomly assigned to receive tiagabine 4, 6, 8, 10 mg or placebo in a randomized, double-blind, parallel-group study. Efficacy was assessed using polysomnography and self-report measures. Safety analyses included measures of residual sedation and adverse events.
  
  
  RESULTS
  A total of 232 patients (31% men; mean age 44.3 years) received study drug. No significant differences were observed between tiagabine and placebo in wake after sleep onset, latency to persistent sleep, or total sleep time. Significantly greater increases from baseline in slow-wave sleep (stages 3 and 4) were found with the 3 highest doses of tiagabine compared with placebo (p < .01). Stage 1 sleep showed a significantly greater decrease from baseline for all doses of tiagabine than for placebo (p < .01). Self-report measures of sleep and daytime function did not differ from placebo, except for poorer ratings on the 10-mg dose. Similarly, psychomotor performance on the 10-mg dose was worsened compared with placebo. Tiagabine was generally well tolerated; dizziness and nausea were the most common adverse events, particularly at the 2 higher doses.
  
  
  CONCLUSIONS
  In adults with primary insomnia, tiagabine significantly increased slow-wave sleep in a dose-dependent manner with a corresponding significant decrease in Stage 1 sleep, whereas no significant differences were observed in wake after sleep onset, latency to persistent sleep, or total sleep time compared with placebo.
authors.affiliation: Sleep Medicine and Research Center, St. Johnś/St. Lukeś Hospitals, St. Louis, MO 63017, USA. jwalsh@stlo.mercy.net
authors.forename: James K
authors.initials: JK
authors.lastname: Walsh
authors.forename: Michael
authors.initials: M
authors.lastname: Perlis
authors.forename: Murray
authors.initials: M
authors.lastname: Rosenthal
authors.forename: Andrew
authors.initials: A
authors.lastname: Krystal
authors.forename: John
authors.initials: J
authors.lastname: Jiang
authors.forename: Thomas
authors.initials: T
authors.lastname: Roth
mesh_terms: D000328:Adult; D015992:Body Mass Index; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D018755:GABA Agonists / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009557:Nipecotic Acids / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D017286:Polysomnography / Q000379:methods; D012720:Severity of Illness Index; D012890:Sleep / Q000187:drug effects*; D007319:Sleep Initiation and Maintenance Disorders / Q000175:diagnosis / Q000188:drug therapy*; D012894:Sleep Stages / Q000187:drug effects; D000078308:Tiagabine
chemical_list: D018755:GABA Agonists; D009557:Nipecotic Acids; D000078308:Tiagabine