Atomoxetine improves sleepiness and global severity of illness but not the respiratory disturbance index in mild to moderate obstructive sleep apnea with sleepiness

Sleep Med. 2008 Jul;9(5):506-10. doi: 10.1016/j.sleep.2007.07.013. Epub 2007 Sep 27.


Background and purpose: Norepinephrine reuptake inhibitors such as protriptyline have been shown to improve sleepiness in sleep apnea, with or without improvement in the respiratory disturbance index (RDI). This study was performed to evaluate whether the selective norepinephrine reuptake inhibitor atomoxetine improves sleepiness, the clinical global impression (CGI) of severity of illness, and the RDI in patients with mild to moderate obstructive sleep apnea with excessive sleepiness.

Methods: Patients aged 18-60 years with RDI (including apneas, hypopneas with desaturations and hypopneas with arousals) >5/h sleep, apnea-hypopnea index (AHI; including apneas, hypopneas with 4% desaturations, but not apneas with arousals) <15/h sleep, and excessive sleepiness (Epworth Sleepiness Scale [ESS]>or=10) received open-label treatment with atomoxetine 40-80 mg HS for 4 weeks, with repeat polysomnography at the end of treatment. Of 20 patients screened, 17 started treatment and 15 completed treatment.

Results: ESS improved from 15.3 to 10.5 and CGI improved from 4.3 to 3.1 (both significant at p<0.01), but there was no significant change in RDI. ESS and CGI improved in a linear fashion across the weeks of treatment. Sleep efficiency and % stage rapid eye movement (REM) sleep were decreased, and % stage 1, awakenings and wake after sleep onset were increased.

Conclusions: Atomoxetine improved sleepiness and the CGI in patients with mild to moderate obstructive sleep apnea with sleepiness. However, it did not improve the RDI.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic Uptake Inhibitors / adverse effects
  • Adrenergic Uptake Inhibitors / therapeutic use*
  • Adult
  • Arousal / drug effects
  • Atomoxetine Hydrochloride
  • Attention / drug effects
  • Disorders of Excessive Somnolence / diagnosis
  • Disorders of Excessive Somnolence / drug therapy*
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Humans
  • Male
  • Middle Aged
  • Polysomnography* / drug effects
  • Propylamines / adverse effects
  • Propylamines / therapeutic use*
  • Sleep Apnea, Obstructive / diagnosis
  • Sleep Apnea, Obstructive / drug therapy*
  • Sleep Stages / drug effects
  • Wakefulness / drug effects
  • Young Adult


  • Adrenergic Uptake Inhibitors
  • Propylamines
  • Atomoxetine Hydrochloride