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Developments in Medications for Sleep Apnea

Sleep allows the body and mind to recharge; without it, the human brain cannot function properly, and the body becomes more susceptible to disease. Sleep apnea involves brief stoppages in breathing that cause a person to wake repeatedly, which over time can increase risk of cardiovascular disease, depression, high blood pressure, and type 2 diabetes (O’Connor, 2019). For those with the condition, nightly sleep becomes a noisy struggle to breathe rather than a period of restoration. The most common type of sleep apnea is known as obstructive sleep apnea (OSA), which increases the risk of complications during surgery, and despite decades of research, there are no approved medications to treat the condition (Brody, 2019). However, in June of 2021, a team of researchers at Flinders University in Australia found promising results for a potential treatment. Their research, first published in the Journal of Physiology, found that a two-drug combination can reduce sleep apnea by at least 30% (Lim et al., 2021).

There are currently only a few therapies for sleep apnea patients. Continuous positive airway pressure (CPAP) therapy works to prevent a person’s airway from collapsing during sleep (Schein, 2014). CPAP machines, which are comprised of a mask, tube, and motor, use mild air pressure to keep the mask wearer’s airways open. While the CPAP therapy approach works for many, the most common side effects include nasal congestion or runny nose, feelings of claustrophobia, and difficulty falling asleep (Bakalar, 2021). Variable and bi-level positive airway pressure (VPAP and BPAP) therapies work similarly.

An alternative approach is a mandibular repositioning device; these are oral appliances designed to keep the airway open by bringing the wearer’s jaw forward or holding their tongue in place (Marques et al., 2019). However, these devices can be expensive, cause jaw pain, and are less reliable than PAP machines (Bakalar, 2021). Surgery is the last resort for sleep apnea: in the most common of these procedures, surgeons remove obstructive tissues that block the airway (Brody, 2019). Cheaper, over-the-counter approaches like nasal decongestant and breathing strips rarely work for diagnosed sleep apnea.

Researchers at Flinders University found that a combination of two medications – butylbromide and reboxetine – kept pharyngeal muscles active during sleep in people with sleep apnea, allowing for improvement in airway collapsibility and more regular and steady breathing (Lim et al., 2021). Butylbromide is an antispasmodic drug, while reboxetine is most often used to treat depression. While the medications had previously been shown to improve upper airway function during sleep for healthy individuals, its effect on sleep apnea severity was unknown until the Flinders researchers completed their study (Flinders Newsdesk, 2021). Out of fifteen original volunteers, twelve otherwise healthy individuals with OSA completed a double-blind, randomized, placebo-controlled trial (Lim et al., 2021). The research team observed participants for two nights. Each participant received either the two-drug combination or placebo immediately prior to sleep; using nasal masks, pneumotachographs (devices that record the rate of airflow), epiglottic pressure sensors, and more, researchers captured data to create estimates of OSA severity between the two groups. “Almost everyone we studied had some improvement in sleep apnea,” said Professor Danny Eckert, lead researcher and Director of Adelaide Institute for Sleep Health at Flinders (Flinders Newsdesk, 2021). “People’s oxygen intake improved. Their number of breathing stoppages was a third or more less.”

The research team will next look at the long-term effects of this drug combination and similar medications. For now, the findings of the recent study bode well for future developments in pharmacological treatment for OSA.

References 

Bakalar, Nicholas. (2021, May 31). For Sleep Apnea, a Mouth Guard May be a Good Alternative to CPAP. The New York Times. https://www.nytimes.com/2021/05/31/well/mind/sleep-apnea-treatment-mouth-guard.html 

Brody, Jane E. (2019, May 27). Sleep Apnea Can Have Deadly Consequences. The New York Times. https://www.nytimes.com/2019/05/27/well/mind/sleep-apnea-can-have-deadly-consequences.html 

Flinders Newsdesk. (2021, July 7). Drug combo cuts severity of sleep apnoea. Flinders University. https://news.flinders.edu.au/blog/2021/07/07/drug-combo-cuts-severity-of-sleep-apnoea/ 

Lim, R., Messineo, L., Grunstein, R.R., Carberry, J.C. and Eckert, D.J. (2021), The noradrenergic agent reboxetine plus the antimuscarinic hyoscine butylbromide reduces sleep apnoea severity: a double-blind, placebo-controlled, randomised crossover trial. J Physiol. https://doi.org/10.1113/JP281912 

Marques, M., Genta, P.R., Azarbarzin, A., Taranto-Montemurro, L., Messineo, L., Hess, L.B., Demko, G., White, D.P., Sands, S.A. and Wellman, A. (2019), Structure and severity of pharyngeal obstruction determine oral appliance efficacy in sleep apnoea. J Physiol, 597: 5399-5410. https://doi.org/10.1113/JP278164 

O’Connor, Anahad. (2019, April 10). A Guide to Sleep Apnea. The New York Timeshttps://www.nytimes.com/guides/well/sleep-apnea-guide 

Schein, A. S., Kerkhoff, A. C., Coronel, C. C., Plentz, R. D., & Sbruzzi, G. (2014). Continuous positive airway pressure reduces blood pressure in patients with obstructive sleep apnea; a systematic review and meta-analysis with 1000 patients. Journal of Hypertension, 32(9), 1762–1773. https://doi.org/10.1097/HJH.0000000000000250