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.
OBJECTIVE
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.
Japan Somnology Center, Neuropsychiatric Research Institute, Tokyo, Japan. inoue@somnology.com
Yuichi
Y
Inoue
Yuji
Y
Takasaki
Yoshihiro
Y
Yamashiro
D000328:Adult; D000368:Aged; D001559:Benzhydryl Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D003131:Combined Modality Therapy / Q000379:methods; D045422:Continuous Positive Airway Pressure / Q000379:methods*; D006970:Disorders of Excessive Somnolence / Q000150:complications / Q000188:drug therapy*; D004311:Double-Blind Method; D064420:Drug-Related Side Effects and Adverse Reactions / Q000150:complications; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D000077408:Modafinil; D010808:Physical Examination; D017286:Polysomnography / Q000379:methods; D020181:Sleep Apnea, Obstructive / Q000150:complications / Q000628:therapy*; D016896:Treatment Outcome; D064690:Wakefulness-Promoting Agents / Q000009:adverse effects / Q000627:therapeutic use*; D055815:Young Adult
D001559:Benzhydryl Compounds; D064690:Wakefulness-Promoting Agents; D000077408:Modafinil
Epworth Sleepiness Scale; Randomized clinical trial; daytime sleepiness; maintenance of wakefulness test; modafinil; nasal continuous positive airway pressure; obstructive sleep apnea; safety