The Role of Pharmacotherapy for Excessive Daytime Sleepiness in OSA: A Changing Landscape?

Excessive daytime sleepiness is a key presenting feature of patients with OSA. When sleepiness remains despite traditional therapies like CPAP, wakefulness-promoting medication may be appropriate. Treating daytime sleepiness directly also may benefit patients who are unable to tolerate CPAP or other mechanical therapies. The growing number of patients with obesity-related OSA may experience sleepiness caused by both OSA and obesity, and weight loss pharmacotherapy may reduce daytime sleepiness.

Several wakefulness promoters are available globally for the indication of residual excessive daytime sleepiness (EDS) in OSA despite CPAP, with some differences in drug access among countries. Recent network meta-analyses have examined the comparative effectiveness of approaches to treat residual EDS in OSA, but clinical guidelines have not been updated since 2013. This review explores the latest evidence on currently available wakefulness promoters and their comparative effectiveness in EDS despite treatment. Evidence for treating sleepiness in the lesser-studied group of patients who are unable to tolerate mechanical therapies for OSA is presented, and the future directions of 2 emerging drug classes are explored, including orexin-2 receptor agonists, with their direct wake-promoting effect, and incretin-based antiobesity agents used in OSA.

We found that existing medications reduce daytime sleepiness in both patients with EDS despite treatment and in patients with OSA who are not using mechanical therapy, but their effectiveness is limited. Further research is required to determine if newly developed orexin-2 receptor agonists and incretin-based obesity medications could change the clinical landscape to treat sleepiness in OSA.