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.
Highlights
Obstructive sleep apnea (OSA) is a common and harmful medical condition that remains undertreated due to poor compliance with the leading therapy, continuous positive airway pressure (CPAP) [1,2]
A recent metanalysis on the effect of surgical weight loss on OSA [27] showed that there is no relationship between the amount of weight loss and apnea-hypopnea index (AHI) reduction in these patients likely because other factors are at play in determining the AHI even when the anatomical defect has been reduced
The patients lost 5.9% more weight (−10.2% from baseline) and their AHI was 36% lower compared to placebo (−71% from baseline of 44.2 events/h) suggesting that this combination could be very helpful in treating obese OSA patients
Summary
Obstructive sleep apnea (OSA) is a common and harmful medical condition that remains undertreated due to poor compliance with the leading therapy, continuous positive airway pressure (CPAP) [1,2]. In the last 15 years, researchers have shown that a number of key pathophysiological traits, or endotypes, contribute to the pathogenesis of OSA [5,7,8,9,10,11] (Figure 1) These include (1) a small, collapsible upper airway (2) reduced dilator muscle responsiveness, (3) reduced arousal threshold, and (4) an oversensitive ventilatory control system (high loop gain). EMGGG : genioglossus electromyography, V response/V disturbance: ratio between the ventilatory response to a preceding ventilatory disturbance, dimensionless While this endotype-based approach has so far been limited to the research setting, recent progresses have allowed measurements of the traits from the clinical polysomnography and will possibly be included in future software packages [13,14,15]. Upper airway muscles activity, may have sedative effects [19]
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