Targeting Endotypic Traits with Medications for the Pharmacological Treatment of Obstructive Sleep Apnea. A Review of the Current Literature

Abstract

Obstructive sleep apnea (OSA) is a highly prevalent condition with few therapeutic options. To date there is no approved pharmacotherapy for this disorder, but several attempts have been made in the past and are currently ongoing to find one. The recent identification of multiple endotypes underlying this disorder has oriented the pharmacological research towards tailored therapies targeting specific pathophysiological traits that contribute differently to cause OSA in each patient. In this review we retrospectively analyze the literature on OSA pharmacotherapy dividing the medications tested on the basis of the four main endotypes: anatomy, upper airway muscle activity, arousal threshold and ventilatory instability (loop gain). We show how recently introduced drugs for weight loss that modify upper airway anatomy may play an important role in the management of OSA in the near future, and promising results have been obtained with drugs that increase upper airway muscle activity during sleep and reduce loop gain. The lack of a medication that can effectively increase the arousal threshold makes this strategy less encouraging, although recent studies have shown that the use of certain sedatives do not worsen OSA severity and could actually improve patients’ sleep quality.

Zolpidem increases sleep efficiency and the respiratory arousal threshold without changing sleep apnoea severity and pharyngeal muscle activity

“…Additionally, increasing arousal threshold with zolpidem might be of benefit in the context of new combination therapy approaches to treat OSA, some of which have unwanted wake promoting properties (Taranto‐Montemurro et al . 2019 b ).…”

“…Given these properties, further work to investigate potential beneficial effects of short-term zolpidem in people with comorbid OSA and insomnia, including to facilitate CPAP tolerance and adherence, are warranted. Additionally, increasing arousal threshold with zolpidem might be of benefit in the context of new combination therapy approaches to treat OSA, some of which have unwanted wake promoting properties (Taranto-Montemurro et al 2019b).…”

“…The Therapeutic Goods Administration regulatory body in Australia classifies sleep apnoea as a contraindication for zolpidem usage (Sanofi-Aventis Australia). These recommendations are based largely on case reports (Mendelson et al 1981), early works on unselected patients (Dolly & Block, 1982) and animal studies (Bonora et al 1985) with concern that these potential negative effects would translate clinically into worse subjective sleep quality and daytime symptoms, with car accidents as a potential life-threatening consequence (Teran-Santos et al 1999;Leufkens et al 2009). However, zolpidem has less next-morning residual effect when compared to benzodiazepines (Uchimura et al 2006).…”

Modulation of TASK-1/3 channels at the hypoglossal motoneuron pool and effects on tongue motor output and responses to excitatory inputs in vivo: implications for strategies for obstructive sleep apnea pharmacotherapy

“…Overall, despite the interest and theoretical potential for TASK channel blockers acting at the hypoglossal motoneuron pool to increase tongue motor tone and provide a new strategic direction of OSA pharmacotherapy, the results of the present studies performed across a range or preparations suggest that this direction is not currently supported, at least with the agents currently available in the public domain. Other strategies also rooted in basic mechanistic studies in pre-clinical animal models have recently proved more effective for OSA pharmacotherapy [ 71 , 72 ].…”

A New Wearable System for Home Sleep Apnea Testing, Screening, and Classification

“…The most used intervention for OSA is the continuous positive airway pressure (CPAP), which opens the collapsed airways and guarantees their patency. Surgery can be a solution in case of anatomical anomalies [19,22]. For people affected by CSA, therapeuthic options are nocturnal supplemental oxygen, adaptive servo-ventilation, bilevel positive airway pressure (BPAP), and acetazolamide.…”