title: Trazodone Effects on Obstructive Sleep Apnea and Non-REM Arousal Threshold.
abstract: BACKGROUND
  A low respiratory arousal threshold is a physiological trait involved in obstructive sleep apnea (OSA) pathogenesis. Trazodone may increase arousal threshold without compromising upper airway muscles, which should improve OSA.
  
  
  OBJECTIVE
  We aimed to examine how trazodone alters OSA severity and arousal threshold. We hypothesized that trazodone would increase the arousal threshold and improve the apnea/hypopnea index (AHI) in selected patients with OSA.
  
  
  METHODS
  Subjects were studied on two separate nights in a randomized crossover design. Fifteen unselected subjects with OSA (AHI ≥ 10/h) underwent a standard polysomnogram plus an epiglottic catheter to measure the arousal threshold. Subjects were studied after receiving trazodone (100 mg) and placebo, with 1 week between conditions. The arousal threshold was calculated as the nadir pressure before electrocortical arousal from approximately 20 spontaneous respiratory events selected randomly.
  
  
  RESULTS
  Compared with placebo, trazodone resulted in a significant reduction in AHI (38.7 vs. 28.5 events/h, P = 0.041), without worsening oxygen saturation or respiratory event duration. Trazodone was not associated with a significant change in the non-REM arousal threshold (-20.3 vs. -19.3 cm H2O, P = 0.51) compared with placebo. In subgroup analysis, responders to trazodone spent less time in N1 sleep (20.1% placebo vs. 9.0% trazodone, P = 0.052) and had an accompanying reduction in arousal index, whereas nonresponders were not observed to have a change in sleep parameters.
  
  
  CONCLUSIONS
  These findings suggest that trazodone could be effective therapy for patients with OSA without worsening hypoxemia. Future studies should focus on underlying mechanisms and combination therapies to eliminate OSA. Clinical trial registered with www.clinicaltrials.gov (NCT 01817907).
authors.affiliation: 1 Division of Pulmonary and Critical Care Medicine, University of California San Diego, La Jolla, CA.
authors.forename: Erik T
authors.initials: ET
authors.lastname: Smales
authors.forename: Bradley A
authors.initials: BA
authors.lastname: Edwards
authors.forename: Pam N
authors.initials: PN
authors.lastname: Deyoung
authors.forename: David G
authors.initials: DG
authors.lastname: McSharry
authors.forename: Andrew
authors.initials: A
authors.lastname: Wellman
authors.forename: Adrian
authors.initials: A
authors.lastname: Velasquez
authors.forename: Robert
authors.initials: R
authors.lastname: Owens
authors.forename: Jeremy E
authors.initials: JE
authors.lastname: Orr
authors.forename: Atul
authors.initials: A
authors.lastname: Malhotra
mesh_terms: D000328:Adult; D000368:Aged; D018687:Antidepressive Agents, Second-Generation / Q000008:administration & dosage; D045422:Continuous Positive Airway Pressure / Q000379:methods*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017286:Polysomnography / Q000379:methods; D012684:Sensory Thresholds / Q000187:drug effects*; D012890:Sleep / Q000187:drug effects / Q000502:physiology*; D020181:Sleep Apnea, Obstructive / Q000503:physiopathology / Q000628:therapy*; D014196:Trazodone / Q000008:administration & dosage*
chemical_list: D018687:Antidepressive Agents, Second-Generation; D014196:Trazodone
keywords: arousal; obstructive sleep apnea pathogenesis; pharmacologic therapy; sedative; sleep-disordered breathing