Effects of hypnotics on obstructive sleep apnea endotypes and severity: Novel insights into pathophysiology and treatment

Impaired upper airway anatomy is the main cause of obstructive sleep apnea (OSA). However, there are other important non-anatomical contributors or “endotypes” including ventilatory control instability, poor pharyngeal dilator muscle responsiveness and waking up too easily to minor respiratory events (low arousal threshold). Recent studies have focused on the potential to target specific OSA causes with novel treatments to reduce OSA severity and improve efficacy with existing non-CPAP therapies which are often suboptimal (e.g., mandibular advancement splints). One novel target is pharmacotherapy with hypnotics to increase the threshold for arousal and reduce OSA severity in the approximately 30% of patients who have a low arousal threshold endotype. This increasing body of work has produced varied and at times unexpected findings which have challenged previous knowledge on the effects of hypnotics on upper airway physiology and breathing during sleep in people with OSA. This review provides a concise overview of the latest research that has investigated the effects of common hypnotics/sedative agents on upper airway physiology and OSA severity and potential implications for OSA pathophysiology, treatment and safety. This includes a summary of the latest knowledge on the effects of hypnotics on OSA endotypes. Priorities for future research are also highlighted.