Emerging drugs for common conditions of sleepiness: obstructive sleep apnea and narcolepsy

Obstructive sleep apnea (OSA) and narcolepsy are sleep disorders associated with high prevalence and high symptomatic burden including prominent sleepiness, daytime dysfunction and poor nocturnal sleep. Both have elevated risk of poor health outcomes. Current therapies are often underutilized, cumbersome, costly or associated with residual symptoms.

This review covers current available therapies for OSA and narcolepsy as well as discusses areas for potential drug development, and agents in the therapeutic pipeline, including the cannabinoid dronabinol (OSA), the histamine inverse agonist/ antagonist pitolisant (narcolepsy), and stimulants with uncertain and/or multiple activities such as JZP-110 and JZP-386 (narcolepsy, possibly OSA). Finally it addresses new approaches and uses for therapies currently on the market such as the carbonic anhydrase inhibitor acetazolamide (OSA).

Both OSA and narcolepsy are conditions of sleepiness for which lifelong treatments are likely to be required. In OSA, while continuous positive airway pressure will likely remain the gold standard therapy for the foreseeable future, there is plenty of room for integrating phenotypes and variants of OSA into therapeutic strategies to lead to better, more personalized disease modification. In narcolepsy, unlike OSA, drug therapy is the current mainstay of treatment. Advances using novel mechanisms to treat targeted symptoms such as sleepiness and/or novel agents that can treat more than one symptom of narcolepsy, hold promise. However, cost, convenience and side effects remain challenges.