Modafinil is indicated to improve wakefulness in patients with excessive sleepiness associated with narcolepsy, shift work sleep disorder (SWSD), and obstructive sleep apnea (OSA) (when used as an adjunct to nCPAP to treat residual excessive sleepiness). The modafinil dose necessary to sustain wakefulness may relate to excessive sleepiness severity. Patients with narcolepsy are usually sleepier than nCPAP-treated OSA patients. This meta-analysis evaluated open-label extension studies to determine whether the modafinil dose necessary to optimize wakefulness differed between the narcolepsy and OSA patient populations.
Patients with narcolepsy or residual excessive sleepiness in nCPAP-treated OSA who had completed 1 of 3 randomized, double-blind, placebo-controlled studies entered open-label extension phases (40 weeks for both narcolepsy studies, 12 months for the OSA study). The effect of modafinil (200-400 mg per day) on excessive sleepiness was assessed using the Epworth Sleepiness Scale (ESS).
478 narcolepsy patients and 266 OSA patients received modafinil in open-label studies; 453 (95%) narcolepsy and 175 (66%) OSA patients completed the studies. Body mass index was 28.8±6.3 kg/m2 in narcolepsy patients versus 36.2±7.6 kg/m2 in OSA patients (p<0.0001). Mean baseline ESS score was 17.4±4.1 in narcolepsy patients versus 14.5±3.6 in OSA patients (p<0.001). Change from baseline in ESS at endpoint was −4.5±4.7 for OSA and −4.4±4.9 for narcolepsy. The percent of patients titrated to average doses of 400, 300, and 200 mg were 50, 34, and 16, respectively, for narcolepsy and 33, 43, and 24 for OSA. Modafinil was well tolerated. Adverse events were similar in both patient populations.
When titrated for both efficacy and tolerability, a greater percentage of patients with narcolepsy were treated at higher doses of modafinil than nCPAP-treated OSA patients with residual excessive sleepiness. This difference may relate to differences in excessive sleepiness at baseline.
Modafinil is effective for treating excessive sleepiness in narcolepsy and OSA (as an adjunct to nCPAP). Knowledge of the effective dose range for different patient populations will assist clinicians in making dosing decisions.Sponsored by Cephalon, Inc.
J.R. Schwartz, Cephalon,