Efficacy and safety of adjunctive modafinil treatment on residual excessive daytime sleepiness among nasal continuous positive airway pressure-treated japanese patients with obstructive sleep apnea syndrome: a double-blind placebo-controlled study

J Clin Sleep Med. 2013 Aug 15;9(8):751-7. doi: 10.5664/jcsm.2912.

Abstract

Study objectives: This double-blind study evaluated the efficacy and safety of modafinil for treating excessive daytime sleepiness in Japanese patients with obstructive sleep apnea syndrome (OSAS).

Methods: Patients with residual excessive sleepiness (Epworth Sleepiness Scale [ESS] ≥ 11) on optimal nasal continuous positive airway pressure (nCPAP) therapy (apnea-hypopnea index ≤ 10) were randomized to either 200 mg modafinil (n = 52) or placebo (n = 62) once daily for 4 weeks. Outcomes included baseline-week 4 changes in ESS total score, sleep latency on maintenance of wakefulness test (SL-MWT), nocturnal polysomnography, Pittsburgh Sleep Quality Index (PSQI), and safety.

Results: All 114 randomized patients completed the study. Mean change in ESS total score (-6.6 vs -2.4, p < 0.001) and SL-MWT (+2.8 vs -0.4 minutes, p = 0.009) were significantly greater with modafinil than with placebo. ESS total score decreased from > 11 to < 11 at the final assessment in 69.2% of modafinil-treated patients and 30.6% of placebo-treated patients (p < 0.001). Corresponding rates at week 1 were 57.7% and 33.9% (p = 0.014). Changes in nocturnal polysomnography, PSQI, and apnea-hypopnea index from baseline to the final assessment were similar in both groups. Adverse drug reactions occurred in 36.5% and 22.6% of patients in the modafinil and placebo groups, respectively (p = 0.146).

Conclusions: Once-daily modafinil was effective and well tolerated for managing residual daytime sleepiness in Japanese OSAS patients with residual excessive daytime sleepiness on optimal nCPAP therapy.

Keywords: Epworth Sleepiness Scale; Randomized clinical trial; daytime sleepiness; maintenance of wakefulness test; modafinil; nasal continuous positive airway pressure; obstructive sleep apnea; safety.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Benzhydryl Compounds / adverse effects
  • Benzhydryl Compounds / therapeutic use*
  • Combined Modality Therapy / methods
  • Continuous Positive Airway Pressure / methods*
  • Disorders of Excessive Somnolence / complications
  • Disorders of Excessive Somnolence / drug therapy*
  • Double-Blind Method
  • Drug-Related Side Effects and Adverse Reactions / complications
  • Electrocardiography / drug effects
  • Female
  • Humans
  • Japan
  • Male
  • Middle Aged
  • Modafinil
  • Physical Examination
  • Polysomnography / methods
  • Sleep Apnea, Obstructive / complications
  • Sleep Apnea, Obstructive / therapy*
  • Treatment Outcome
  • Wakefulness-Promoting Agents / adverse effects
  • Wakefulness-Promoting Agents / therapeutic use*
  • Young Adult

Substances

  • Benzhydryl Compounds
  • Wakefulness-Promoting Agents
  • Modafinil