Pharmacotherapies for obstructive sleep apnea: how close are we?

Obstructive sleep apnea is a prevalent disorder associated with significant neurobehavioral and cardiovascular morbidities. At present, however, there are no widely effective, well-tolerated pharmacotherapies for obstructive sleep apnea. The pathogenesis of this disorder predicts that sleep apnea should respond to drug therapies. Specifically, respiration during waking in persons with sleep apnea is normal, while collapse of the upper airway occurs exclusively in sleep. This state-dependency in upper airway patency suggests state-dependent changes in neurochemical control of the upper airway dilator motoneurons, and this, in turn, suggests that appropriate medications would maintain upper airway dilator function in sleep and prevent sleep related collapse of the upper airway. The past few years have brought significant insight into the neural mechanisms governing upper airway dilator muscle function. This article provides updates on neurochemical mechanisms, emphasizing a role for serotonergic control, and reviews recent drug therapy trials for sleep apnea. We are currently well poised to develop effective pharmacotherapies for obstructive sleep apnea, with opportunities to target several regions involved in respiratory control.