title: Trazodone increases the respiratory arousal threshold in patients with obstructive sleep apnea and a low arousal threshold.
abstract: OBJECTIVE
  The effect of common sedatives on upper airway physiology and breathing during sleep in obstructive sleep apnea (OSA) has been minimally studied. Conceptually, certain sedatives may worsen OSA in some patients. However, sleep and breathing could improve with certain sedatives in patients with OSA with a low respiratory arousal threshold. This study aimed to test the hypothesis that trazodone increases the respiratory arousal threshold in patients with OSA and a low arousal threshold. Secondary aims were to examine the effects of trazodone on upper airway dilator muscle activity, upper airway collapsibility, and breathing during sleep.
  
  
  METHODS
  Patients were studied on 4 separate nights according to a within-subjects cross-over design.
  
  
  METHODS
  Sleep physiology laboratory.
  
  
  METHODS
  Seven patients with OSA and a low respiratory arousal threshold.
  
  
  METHODS
  In-laboratory polysomnograms were obtained at baseline and after 100 mg of trazodone was administered, followed by detailed overnight physiology experiments under the same conditions. During physiology studies, continuous positive airway pressure was transiently lowered to measure arousal threshold (negative epiglottic pressure prior to arousal), dilator muscle activity (genioglossus and tensor palatini), and upper airway collapsibility (Pcrit).
  
  
  RESULTS
  Trazodone increased the respiratory arousal threshold by 32 ± 6% (-11.5 ± 1.4 versus -15.3 ± 2.2 cmH2O, P < 0.01) but did not alter the apnea-hypopnea index (39 ± 12 versus 39 ± 11 events/h sleep, P = 0.94). Dilator muscle activity and Pcrit also did not systematically change with trazodone.
  
  
  CONCLUSIONS
  Trazodone increases the respiratory arousal threshold in patients with obstructive sleep apnea and a low arousal threshold without major impairment in dilator muscle activity or upper airway collapsibility. However, the magnitude of change in arousal threshold was insufficient to overcome the compromised upper airway anatomy in these patients.
authors.affiliation: Brigham and Women's Hospital, Division of Sleep Medicine, Sleep Disorders Program and Harvard Medical School, Boston, MA ; Neuroscience Research Australia (NeuRA), and the School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: Danny J
authors.initials: DJ
authors.lastname: Eckert
authors.affiliation: Brigham and Women's Hospital, Division of Sleep Medicine, Sleep Disorders Program and Harvard Medical School, Boston, MA ; Pulmonary and Critical Care Division, University of California San Diego, La Jolla, CA.
authors.forename: Atul
authors.initials: A
authors.lastname: Malhotra
authors.affiliation: Brigham and Women's Hospital, Division of Sleep Medicine, Sleep Disorders Program and Harvard Medical School, Boston, MA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Wellman
authors.affiliation: Brigham and Women's Hospital, Division of Sleep Medicine, Sleep Disorders Program and Harvard Medical School, Boston, MA.
authors.forename: David P
authors.initials: DP
authors.lastname: White
mesh_terms: D000328:Adult; D001143:Arousal / Q000187:drug effects* / Q000502:physiology; D045422:Continuous Positive Airway Pressure; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D017286:Polysomnography; D012119:Respiration / Q000187:drug effects*; D012137:Respiratory System / Q000187:drug effects / Q000503:physiopathology; D012890:Sleep / Q000187:drug effects / Q000502:physiology; D020181:Sleep Apnea, Obstructive / Q000188:drug therapy / Q000503:physiopathology* / Q000628:therapy*; D014196:Trazodone / Q000494:pharmacology* / Q000627:therapeutic use; D014851:Wakefulness / Q000187:drug effects
chemical_list: D006993:Hypnotics and Sedatives; D014196:Trazodone
keywords: Arousal; lung; muscles; respiratory physiology; sedative; sleep-disordered breathing; upper airway