Modafinil/armodafinil in the treatment of excessive daytime sleepiness

Introduction Excessive daytime sleepiness (EDS), a common problem that affects a substantial portion of the general population, is often the cardinal presenting feature of sleep disorders such as narcolepsy, shift work disorder (SWD), and obstructive sleep apnea (OSA). Modafinil, an effective wake-promoting agent with good safety and tolerability measures in addition to having low abuse potential, has been studied extensively in the treatment of daytime sleepiness associated with these sleep disorders, as well as other medical conditions such as Parkinson's disease, multiple sclerosis, depression, and chronic fatigue syndrome. More recently, a longer form of modafinil, armodafinil, the R-enantiomer, has been approved for the treatment of narcolepsy, SWD, and EDS associated with OSA. The following is a review of the therapeutic efficacy, tolerability and mode of action of modafinil and armodafinil for approved and off-label treatment of excessive sleepiness. Modafinil for the treatment of excessive sleepiness associated with OSA The treatment of choice for obstructive sleep apnea is continuous positive airway pressure (CPAP), which when used effectively, can alleviate respiratory disturbances, oxygen desaturations, and daytime sleepiness. However, a significant number of patients with treated obstructive sleep apnea continue to experience residual excessive sleepiness. Modafinil has been studied as a wake-promoting agent to alleviate symptoms of daytime sleepiness in patients with OSA treated by CPAP. A 4-week randomized, double-blind, placebo-controlled, parallel study evaluated the efficacy of modafinil (200 mg/d, week 1; 400 mg/d, weeks 2–4) in 157 patients with obstructive sleep apnea (Respiratory Disturbance Index (RDI) ≥ 15) and residual daytime sleepiness while compliant with CPAP therapy.