title: Effects of Tiagabine on Slow Wave Sleep and Arousal Threshold in Patients With Obstructive Sleep Apnea.
abstract: Obstructive sleep apnea (OSA) severity is markedly reduced during slow-wave sleep (SWS) even in patients with a severe disease. The reason for this improvement is uncertain but likely relates to non-anatomical factors (i.e. reduced arousability, chemosensitivity, and increased dilator muscle activity). The anticonvulsant tiagabine produces a dose-dependent increase in SWS in subjects without OSA. This study aimed to test the hypothesis that tiagabine would reduce OSA severity by raising the overall arousal threshold during sleep.
  
  
  
  After a baseline physiology night to assess patients' OSA phenotypic traits, a placebo-controlled, double-blind, crossover trial of tiagabine 12 mg administered before sleep was performed in 14 OSA patients. Under each condition, we assessed the effects on sleep and OSA severity using standard clinical polysomnography.
  
  
  
  Tiagabine increased slow-wave activity (SWA) of the electroencephalogram (1-4 Hz) compared to placebo (1.8 [0.4] vs. 2.0 [0.5] LogμV2, p = .04) but did not reduce OSA severity (apnea-hypopnea index [AHI] 41.5 [20.3] vs. 39.1 [16.5], p > .5). SWS duration (25 [20] vs. 26 [43] mins, p > .5) and arousal threshold (-26.5 [5.0] vs. -27.6 [5.1] cmH2O, p = .26) were also unchanged between nights.
  
  
  
  Tiagabine modified sleep microstructure (increase in SWA) but did not change the duration of SWS, OSA severity, or arousal threshold in this group of OSA patients. Based on these findings, tiagabine should not be considered as a therapeutic option for OSA treatment.
authors.affiliation: Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham & Women's Hospital & Harvard Medical School, Boston, MA.
authors.forename: Luigi
authors.initials: L
authors.lastname: Taranto-Montemurro
authors.affiliation: Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham & Women's Hospital & Harvard Medical School, Boston, MA.|Department of Allergy, Immunology and Respiratory Medicine and Central Clinical School, The Alfred and Monash University, Melbourne, VIC Australia.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Sands
authors.affiliation: Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham & Women's Hospital & Harvard Medical School, Boston, MA.|Sleep and Circadian Medicine Laboratory, Department of Physiology Monash University, Melbourne, VIC, Australia.|School of Psychological Sciences and Monash Institute of Cognitive and Clinical Neurosciences, Monash University, Melbourne, VIC, Australia.
authors.forename: Bradley A
authors.initials: BA
authors.lastname: Edwards
authors.affiliation: Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham & Women's Hospital & Harvard Medical School, Boston, MA.
authors.forename: Ali
authors.initials: A
authors.lastname: Azarbarzin
authors.affiliation: Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham & Women's Hospital & Harvard Medical School, Boston, MA.
authors.forename: Melania
authors.initials: M
authors.lastname: Marques
authors.affiliation: Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham & Women's Hospital & Harvard Medical School, Boston, MA.
authors.forename: Camila
authors.initials: C
authors.lastname: de Melo
authors.affiliation: Neuroscience Research Australia (NeuRA) and the University of New South Wales, Randwick, Sydney, Australia.
authors.forename: Danny J
authors.initials: DJ
authors.lastname: Eckert
authors.affiliation: Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham & Women's Hospital & Harvard Medical School, Boston, MA.
authors.forename: David P
authors.initials: DP
authors.lastname: White
authors.affiliation: Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham & Women's Hospital & Harvard Medical School, Boston, MA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Wellman
mesh_terms: D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000627:therapeutic use; D001143:Arousal / Q000187:drug effects / Q000502:physiology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004569:Electroencephalography / Q000187:drug effects / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009557:Nipecotic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D017286:Polysomnography / Q000379:methods; D012890:Sleep / Q000187:drug effects / Q000502:physiology*; D020181:Sleep Apnea, Obstructive / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology*; D000078308:Tiagabine; D016896:Treatment Outcome; D014851:Wakefulness / Q000187:drug effects / Q000502:physiology
chemical_list: D000927:Anticonvulsants; D009557:Nipecotic Acids; D000078308:Tiagabine
keywords: arousal threshold; sleep-disordered breathing; slow-wave sleep; tiagabine