Obstructive Sleep Apnea

by Stephen Beesley, PhD

During my teens and early twenties, I became progressively aware that I was waking up more fatigued than when I initially went to sleep. It would take me the majority of the first waking hour to finally feel 'awake'. Having completed my graduate studies in circadian biology, I considered myself relatively well educated on matters concerning sleep, yet I was ignorant of sleep apnea and its impact on day-to-day life. It wasn't until my mid-30s and after my daughter was born that I sought medical advice (at my wife's behest). It turned out to be a significant leap forward to better and more restful sleep. I was diagnosed with mild obstructive sleep apnea (OSA), where I would stop breathing (the apnea part) around 8 times per hour. A number, on first hearing, sounded somewhat more than the 'mild' diagnosis that was given; however, upon investigation, I discovered that this number can go upwards of 30, leading to a multitude of adverse effects. I considered myself lucky. I was given the most common and, I suppose, the least invasive treatment available, a Continuous Positive Airway Pressure (CPAP) machine, although not without its particular set of challenges. That said, after persevering for a good 6 months, I adjusted to the positive pressure, and my sleep and daytime hours were significantly improved, to the point that I was waking up refreshed for the first time in a good 20 years. It worked. However, one comment struck me as I was being fitted for the CPAP unit. I asked how long I will need to use this machine for. Shockingly, the answer was 'for life'. That was it! No mention of other options, treatments or therapies, just 'for life'.

So what is OSA?

OSA is a common disease with close to a billion people worldwide affected (ClevelandClinic.org). This is a remarkable number given a world population of 8.2 billion. OSA is defined by repeated episodes of partial or complete upper airway collapse during sleep, leading to cyclic intermittent hypoxia (low oxygen), exaggerated intrathoracic pressure swings (breathing in and out becomes exaggerated), and sleep fragmentation (waking up multiple times per night) (Balachandran, JS et al., 2014). These OSA episodes can result in excessive daytime sleepiness, leading to an increased risk of accidents, especially motor vehicle accidents; increased risk of hypertension and coronary artery disease, an increased risk of metabolic disease and cognitive impairment (Levy, P et al, 2015). Overall, OSA can have a profound negative effect on a person's quality of life. In addition to the primary patient, the effects of OSA can also negatively impact their partner, friends and colleagues.

Risk Factors Associated with OSA

Whilst obesity is cited as the main risk factor of OSA and a direct correlation has been shown between an increase in body mass index (BMI) and the apnea-hypopnea index (AHI) (Peppard, PE et al., 2013), it is not the only risk factor. A family history of OSA, simply being male, the use (even moderate use) of alcohol and opiates, and craniofacial abnormalities are all associated risk factors (Abid, R et al., 2014). Therefore, identifying first that you have sleep impairment, then seeking medical professional help and working closely with them to identify the root cause of your OSA is very important. Being armed with the knowledge to ask insightful questions regarding your health allows for a more accurate diagnosis and treatment options.

Treatment Options

My own ongoing treatment for OSA is the CPAP machine, yet this go-to treatment option needs to be re-evaluated. As in my case, the effectiveness of the CPAP is high (albeit taking some time to adjust and adapt to the setup); however, general long-term compliance is low and lacks a patient-specific approach to care (Abid, R et al., 2014). Indeed, there are other options available to treat OSA. Treatments beyond or in conjunction with the CPAP include lifestyle modification, positional therapy, maxillofacial surgery, hypoglossal nerve stimulation, and pharmacological solutions.

Whilst a high BMI may not be the only cause, general health always benefits from a more moderate BMI and is often the first option to consider when dealing with OSA. Weight loss has been shown to decrease AHI, improve overall sleep quality, and decrease daytime sleepiness (Abid, R et al., 2014). Furthermore, in late 2024, the US Food and Drug Administration (FDA) approved Zepbound (tirzepatide; a GLP-1 agonist) for the treatment of moderate to severe OSA in adults with obesity (Mifsud, C et al., 2025 and FDA.gov). This marks the first drug to treat OSA and marks a major shift in thinking from a symptom management approach to a targeted weight-loss approach.

Here, we bridge the gap between lifestyle modifications and pharmacological solutions can and use them in combination treatment to better support the patient. Other potential (not yet FDA-approved) pharmacological solutions include Fluoxetine, a serotonin reuptake inhibitor (SSRI) used to treat depression. SSRIs have been studied as a method of treating OSA and have been found to significantly decrease AHI from events per hour in patients treated with Fluoxetine relative to untreated control groups (Hansel, D et al., 1991). The combination of Atomoxetine and Oxybutynin is another ongoing (yet unapproved) option. Weak muscle tone in the throat often leads to collapse during sleep, blocking the airway. Atomoxetine increases norepinephrine and boosts muscle activity. Oxybutynin works synergistically with atomoxetine to stabilize the upper airway during sleep and reduce AHI (Taranto-Montemurro L et al., 2019).

Positional therapy is simple in theory yet challenging in practice. It involves lying on one's side to prevent upper airway collapse or blockage during sleep. This can be achieved with a simple tennis ball taped to your back to make it uncomfortable to sleep supine (on your back) (Bignold J et al., 2009). This form of therapy is not recommended for all and not for those with shoulder issues. Also, long-term compliance is low due to the limitation of sleep position and potential sleep loss due to a remedy as well as the disorder (Oksenberg A et al., 1997 and Bignold J et al., 2009).

A more invasive technique is to have surgery on the upper airway, which aims to improve the general anatomy to prevent pharyngeal collapse. The most widely used form of upper airway surgery is uvulopalatopharyngoplasty (UPPP). UPPP is used to prevent pharyngeal collapse and increase the overall volume of the throat through removal of the uvula and soft palate. A tonsillectomy is often added to this surgery to further improve the airway opening during sleep (Abid R et al., 2024). In an analysis of almost 40 UPPP studies, the authors found that there was an average reduction in AHI score by 18.5 (Stuck B et al., 2018). This is a significant improvement to overall sleep and can be an effective therapeutic option.

Another surgical technique is hypoglossal nerve stimulation. A technique where there is electrical stimulation of the hypoglossal nerve, which causes the tongue to protrude and stiffen against the anterior pharyngeal wall (back of the throat), significantly increasing the diameter of the upper airway. This intervention is FDA-approved and has had a significant impact on AHI scores, with a 70% reduction in apnea events reported in some instances (Strollo P et al., 2014).

Conclusion

OSA is a disorder that affects the best part of 1 billion people, with the majority being unaware that they are affected. This has a tremendous knock-on effect for both the patient and those who are closely connected (family, friends, and co-workers), even more so if neither party is aware of the underlying diagnosis. There are mechanical, surgical, and passive treatment options, together with a pharmacological approach to improve causal factors. The one-size-fits-all CPAP is not and should not be the only 'for life' option that was told to me at the beginning of my diagnosis. Talking honestly about options with your physician is a must; there are more treatments to be considered and evaluated, and more will emerge as research and understanding progress.

References

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2. https://my.clevelandclinic.org/health/diseases/24443-obstructive-sleep-apnea-osa

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6. https://www.fda.gov/news-events/press-announcements/fda-approves-first-medication-obstructive-sleep-apnea

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