Review: Hypnotics for the Treatment of Obstructive Sleep Apnea Endotypes

The researchers reviewed advancements and current knowledge about the use of hypnotics in therapy for obstructive sleep apnea.

Recent studies have assessed the efficacy of using hypnotic agents for the treatment of obstructive sleep apnea (OSA) endotypes. Advancements and current knowledge about the use of hypnotics in OSA therapy were reviewed in an article published in Sleep Medicine Reviews.

The non-anatomical endotypes which contribute to symptoms of OSA among 70% of patients include unstable respiratory control, low pharyngeal dilator muscle responsiveness, and/or low arousal threshold. The first-line therapy for OSA, continuous positive airway pressure, has low adherence and as such, recent studies have focused on novel therapeutics targeting endotypes.

Results from recent studies have determined that long-standing beliefs about hypnotics may not be in fact true. For instance, there has been no evidence to suggest pharyngeal muscle activity is impaired during sleep, nor do hypnotics exacerbate OSA severity or next-day perceived sleepiness.

Instead, hypnotics have been shown to have varied effects on sleep depending on the individual patient’s underlying pathophysiology, the dosage, and drug class.

Most hypnotics increase respiratory arousal threshold among ~20%-30%. Zolpidem was observed to improve sleep efficiency by ~10% and may be effective among patients with comorbid insomnia. Eszopiclone was observed to decrease arousal frequency and apnea-hypopnea index.

However, among individuals who are morbidly obese, have very severe OSA, baseline major overnight hypoxemia, or higher respiratory arousal threshold, there was an increased risk for a worsening of overnight hypoxemia. It is unlikely that patients with these symptoms or a morbidly obese comorbidity would be good candidates for using hypnotics to treat their OSA.

These recent studies also reported conflicting evidence about next-day objective alertness on the basis of a driving simulation. Although evidence does not suggest next-day sleepiness was affected, it remains unclear whether hypnotics decrease alertness.

The specific pathophysiological interactions between hypnotics and differing OSA endotypes remains poorly understood and requires more research. Additional studies are needed to determine whether hypnotics may be used as a combinatorial therapy with other standard OSA treatments or with sleep promoting agents.

The data presented in this review indicated hypnotics may be useful for the treatment of some endotypes of OSA, potentially increasing respiratory arousal threshold. Additional studies are needed to explore the efficacy of combinatorial therapies and to determine best practices for patient stratification.

Disclosure: An author declared affiliations with industry. Please refer to the original article for a full list of disclosures.


Carter SG, Eckert DJ. Effects of hypnotics on obstructive sleep apnea endotypes and severity: Novel insights into pathophysiology and treatment. Sleep Med Rev. Published online April 22, 2021. doi:10.1016/j.smrv.2021.101492

This article originally appeared on Psychiatry Advisor