Nothwithstanding regular use of nasal continuous positive airway pressure (nCPAP), some patients with obstructive sleep apnea (OSA) experience residual excessive sleepiness. In double-blind studies, modafinil, a novel wake-promoting agent, significantly improves wakefulness in patients with OSA who regularly use nCPAP. This 12-month open-label extension study evaluated long-term treatment with modafinil for residual excessive sleepiness in patients with OSA who were using nCPAP.
Eligible patients from a 12-week, randomized, double-blind, placebo-controlled study were enrolled in a 12-month, open-label extension trial. Modafinil was administered at either 200 mg/day, 300 mg/day, or 400 mg/day (adjusted clinically). Efficacy assessments included the epworth sleepiness scale (ESS) every three months, and the Functional Outcomes of Sleep Questionnaire (FOSQ) at Month 12 (or final visit).
266 patients entered the open-label period; 175 (66%) completed the study. Modafinil significantly improved self-reporting wakefulness (assessed by ESS), at all time points. Mean changes (±SD) in ESS scores from baseline (baseline score, 14.5±3.6) at Months 3, 6, 9, and 12 were −5.7±4.5, −5.3±4.4, −5.4±4.6, and −4.5±4.7, respectively (p<0.01). Modafinil significantly improved functional status, measured as the mean change from baseline to final visit in the total score on FOSQ (increased 14% from baseline; p<0.01). Long-term modafinil treatment was well tolerated. The most frequently reported adverse events (≥5%) were infection (11%), nervousness (9%), headache (9%), accidental injury (8%), sinusitis (7%), rhinitis (7%), depression and anxiety (6% each), and insomnia and dizziness (5% each); most were mild or moderate in severity.CONCLUSIONS: Modafinil increased self-reported wakefulness, improved functional status, and was well-tolerated during 12-months treatment in nCPAP compliant patients with OSA who experienced residual sleepiness.
Modafinil is effective for long term use as a good adjunctive therapy to augment nCPAP to improve wakefulness and functional status in patients with OSA.
M. Hirshkowitz, None. Supported by Cephalon, Inc., West Chester, PA