Obstructive sleep apnea (OSA), a common cause of excessive sleepiness, is associated with impaired mood and other negative outcomes. Nasal continuous positive airway pressure (nCPAP), a standard treatment for OSA, effectively improves airway patency, functional status, and excessive sleepiness. However, some patients experience residual excessive sleepiness even with regular nCPAP use. The novel wake-promoting agent modafinil is indicated for excessive sleepiness associated with narcolepsy, shift work sleep disorder, and residual excessive sleepiness in OSA as an adjunct to nCPAP. We report two double-blind studies of adjunct modafinil for residual excessive sleepiness in OSA patients using nCPAP.
Patients with OSA and residual excessive sleepiness [Epworth Sleepiness Scale (ESS) score ≥10 at screening] despite good nCPAP therapeutic adherence were enrolled into a 4-week (n=157) or 12-week (n=327) double-blind, placebo-controlled study. Patients were randomized to modafinil 200 or 400 mg (12-week study) or 400 mg (4-week study) or placebo. Efficacy assessments included the ESS, Clinical Global Impression of Change (CGI-C), and Functional Outcomes of Sleep Questionnaire (FOSQ).
446 patients received treatment (modafinil 200 mg/day, n=99; modafinil 400 mg/day, n=167; placebo, n=180). Modafinil significantly improved wakefulness compared with placebo on the ESS (baseline [SD]: 15.0 [3.31] modafinil, 14.6 [2.99] placebo vs final visit: 10.5 [5.06] modafinil, 12.7 [4.13] placebo; p<0.0001). Modafinil at least minimally improved overall clinical condition for 65% of patients versus 36% receiving placebo (CGI-C; p<0.0001). Modafinil improved quality of life (FOSQ total score change from baseline: 2.0 [2.45] modafinil vs 1.0 [1.96] placebo; p<0.0001). 292 patients receiving modafinil were included in the safety analysis set. Modafinil was well tolerated. Most common adverse events were headache (n=73, 25%), infection (n=34, 12%), and nausea (n=29, 10%).
Modafinil significantly improves wakefulness, overall clinical condition, and quality of life in patients with OSA with residual excessive sleepiness despite nCPAP therapy.
Modafinil is a well-tolerated therapy that will assist clinicians in safely and effectively treating residual excessive sleepiness in patients with OSA who adhere to the prescribed nCPAP therapy regimen.
J.R. Schwartz, Cephalon