title: Modafinil improves daytime sleepiness in patients with mild to moderate obstructive sleep apnoea not using standard treatments: a randomised placebo-controlled crossover trial.
abstract: BACKGROUND
  Patients with mild to moderate obstructive sleep apnoea (OSA) commonly suffer excessive daytime sleepiness. Continuous positive airway pressure (CPAP) has limited effectiveness in reducing sleepiness in milder OSA. Modafinil is a wake-promoting drug licensed to treat residual sleepiness in CPAP-treated OSA. We hypothesised that modafinil may effectively treat sleepiness in untreated mild to moderate OSA.
  
  
  METHODS
  Untreated sleepy men with mild to moderate OSA (age 18-70, apnoea-hypopnoea index (AHI) 5-30/h, Epworth Sleepiness Scale (ESS) ≥10) were randomised to receive 200 mg modafinil or matching placebo daily for 2 weeks before crossing over to the alternative treatment after a minimum 2-week washout. Mixed model analysis of variance was used to compare the changes on modafinil to placebo while classifying all randomised patients as random factors.
  
  
  RESULTS
  32 patients were randomised (mean (SD) AHI 13 (6.4)/h, age 47 (10.7) years, ESS 13.6 (3.3), body mass index 28.2 (3.6) kg/m(2)), 29 of whom (91%) completed the trial. The primary outcome (ESS) improved more on modafinil than placebo (3.6 points, 95% CI 1.3 to 5.8, p=0.003) and the secondary outcome (40-min driving simulator performance) also improved more on modafinil than placebo (steering deviation 4.7 cm, 95% CI 0.8 to 8.5, p=0.018). Psychomotor Vigilance Task reciprocal reaction time improved significantly over placebo (0.15 (1/ms), 95% CI 0.03 to 0.27, p=0.016). Improvements on the Functional Outcomes of Sleep Questionnaire were not significant (5.3 points over placebo, 95% CI -1 to 11.6, p=0.093).
  
  
  CONCLUSIONS
  Modafinil significantly improved subjective sleepiness in patients with untreated mild to moderate OSA. The size of this effect is clinically relevant at 3-4 ESS points of improvement compared with only 1-2 points in CPAP clinical trials. Driving simulator performance and reaction time also improved on modafinil.
  
  
  BACKGROUND
  ACTRN#12608000128392.
authors.affiliation: The NHMRC Centre for Integrated Research and Understanding of Sleep (CIRUS), The University of Sydney, , Sydney, New South Wales, Australia.
authors.forename: Julia L
authors.initials: JL
authors.lastname: Chapman
authors.forename: Liora
authors.initials: L
authors.lastname: Kempler
authors.forename: Catherina L
authors.initials: CL
authors.lastname: Chang
authors.forename: Shaun C
authors.initials: SC
authors.lastname: Williams
authors.forename: Sheila
authors.initials: S
authors.lastname: Sivam
authors.forename: Keith K H
authors.initials: KK
authors.lastname: Wong
authors.forename: Brendon J
authors.initials: BJ
authors.lastname: Yee
authors.forename: Ronald R
authors.initials: RR
authors.lastname: Grunstein
authors.forename: Nathaniel S
authors.initials: NS
authors.lastname: Marshall
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001559:Benzhydryl Compounds / Q000627:therapeutic use*; D018592:Cross-Over Studies; D006970:Disorders of Excessive Somnolence / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077408:Modafinil; D011597:Psychomotor Performance / Q000187:drug effects; D011788:Quality of Life; D020181:Sleep Apnea, Obstructive / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D012894:Sleep Stages; D016896:Treatment Outcome; D064690:Wakefulness-Promoting Agents / Q000627:therapeutic use*
chemical_list: D001559:Benzhydryl Compounds; D064690:Wakefulness-Promoting Agents; D000077408:Modafinil