As much as the COVID-19 pandemic appears to have engulfed us and subsumed the world, certain other epidemics continue to fester, albeit quietly. The opiate crisis has affected communities everywhere and is one such smouldering healthcare concern. While it may have faded from the news headlines, the ailment has clearly not been eradicated. Opioids remain a serious danger to our society.

Recent evidence suggests that in a bid to numb their pain, direct and indirect sufferers of COVID-19 may have resorted to opiate use. Yet, we know that this will not be beneficial in the long run. Myriad unintended and deleterious consequences of chronic opioid use will likely emerge again, in the not so distant future.

So how do opioids and sleep apnea relate?

Numerous studies[1], [2], [3] have also implicated opioids as a contributory factor to sleep-disordered breathing. A specific but less recognized form of sleep apnea known as central sleep apnea (CSA) is often attributed to opioids, among a few other well-known causal factors for the condition. Mortality attributed to this form of central sleep apnea has been reported to be as high as 33% in some cohorts. That means, one in every three persons dying, among a group of patients taking long acting opioid medications. A truly scary statistic.

Unfortunately, for the most part, central sleep apnea has been largely poorly detected, insufficiently monitored and as such, inadequately treated. Effective, sustainable treatment or control of such a silent killer has eluded sleep medicine for decades, while progression of the opioid crisis has been relentless.

Could a solution for sleep disordered breathing associated with opioid use come from an unexpected breakthrough?  

Recent reports[4], [5] suggest that a hormone called leptin, produced naturally by fat cells in our bodies, may hold the key to alleviating the genuinely life-threatening problem of opioid-induced sleep disordered breathing.

What is leptin, and what is its role in our body?

Simply stated, leptin is a protein produced by fat cells in humans and animals.

Leptin is believed to be primarily an appetite-regulating hormone. Deficiency of the hormone or resistance to its effects is thought to be responsible in part, for obesity. Essentially, low levels of leptin are associated with poor satiety. An insatiable appetite promotes excessive calorie intake. This in turn causes uncontrolled weight gain. Being overweight or obese is a definite risk factor for obstructive sleep apnea, diabetes mellitus and other chronic health problems.

Further, leptin is thought to have several positive effects on breathing. These include helping the lungs to exchange oxygen and carbon dioxide better. 

More importantly, the hormone helps keep our upper airway open during sleep. As such, deficiency of leptin or ineffective leptin effect as observed in obesity, heightens the risk of an unstable airway while we sleep. Paradoxically, obstructive sleep apnea is associated with leptin resistance.

Leptin and obesity – how is it all connected?

In a more complex way, excess leptin in the body has been observed in sleep apnea patients. This is associated with resistance of the body to the effects of leptin, similar to insulin resistance which very well known to occur in obese individuals who then suffer from diabetes.

Effects of opioids on breathing during sleep

During sleep, opioids have been shown to impair a regular breathing pattern, even in persons without sleep-disordered breathing. As depicted below, such respiratory depression caused by opioids aggravates an already unstable airway that is observed during sleep, in individuals who suffer from sleep apnea.

Such unstable airways are highly prone to further compromise. Regular exchange of oxygen and carbon dioxide fails to occur, leading to fatal events described as opioid-related death. This can be potentially mitigated with a high degree of clinical suspicion, early diagnosis and initiation of treatment.

The Challenge

The vast majority of sleep apnea patients are undiagnosed. Fortunately, those who use opioids (prescribed or recreational) are often aware that they consume these medications. While they may have minimal control of their opioid use, help is now at hand for sleep-related breathing problems arising as a consequence of this widely used class of drugs.

However, treatment of one form of sleep apnea does not necessarily improve other co-existing forms of sleep-disordered breathing. While central sleep apnea can be successfully treated by discontinuation of chronic opioid use, co-existent obstructive sleep apnea often persists, especially in the presence of other major risk factors such as obesity.

Also, some of the most effective and currently available modes of treatment for sleep apnea are not always acceptable to all patients with sleep apnea. This has led to an active search for effective, user-friendly treatment options for sleep apnea.

A promising future

Are we getting closer to the day when a nasal spray could be available as an antidote for some forms of Sleep Apnea? Recent animal studies point to such a reality.

An intranasal spray of leptin has been shown to decrease the frequency of apneas, improve obstructive sleep apnea and prevent opioid-induced respiratory depression during sleep in patients with obesity. Firstly, it is important to find out if you suffer from obstructive sleep apnea. Ognomy can help as we provide fully remote diagnosis, testing and treatment of sleep apnea from the comfort of your home.

Explore Ognomy.com to find out more or install the app to meet with one of our board-certified sleep doctors. Better sleep is simply better health!

 

 

 

[1] Chronic Opioid Therapy and Sleep: An American Academy of Sleep Medicine Position Statement. Rosen IM, Aurora RN, Kirsch DB, Carden KA, Malhotra RK, Ramar K, Abbasi-Feinberg F, Kristo DA, Martin JL, Olson EJ, Rosen CL, Rowley JA, Shelgikar AV; American Academy of Sleep Medicine Board of Directors.J Clin Sleep Med. 2019 Nov 15;15(11):1671-1673.
[2] Opioids Cause Central and Complex Sleep Apnea in Humans and Reversal With Discontinuation: A Plea for Detoxification. Javaheri S, Patel S.J Clin Sleep Med. 2017 Jun 15;13(6):829-833.
[3] Obstructive sleep apnea and chronic opioid use. Guilleminault C, Cao M, Yue HJ, Chawla P.Lung. 2010 Dec;188(6):459-68. 
[4] Intranasal Leptin Prevents Opioid-induced Sleep-disordered Breathing in Obese Mice. Freire C, Pho H, Kim LJ, Wang X, Dyavanapalli J, Streeter SR, Fleury-Curado T, Sennes LU, Mendelowitz D, Polotsky VY.Am J Respir Cell Mol Biol. 2020 Oct;63(4):502-509.
[5] Intranasal Leptin Relieves Sleep-disordered Breathing in Mice with Diet-induced Obesity. Berger S, Pho H, Fleury-Curado T, Bevans-Fonti S, Younas H, Shin MK, Jun JC, Anokye-Danso F, Ahima RS, Enquist LW, Mendelowitz D, Schwartz AR, Polotsky VY.Am J Respir Crit Care Med. 2019 Mar 15;199(6):773-783.