Summary: Two existing medications have been repurposed to treat sleep apnea. Researchers report the medications reduce symptoms of sleep apnea by 30%.
Source: The Physiological Society
New research published in The Journal of Physiology shows that researchers have successfully repurposed two existing medications to reduce the severity of sleep apnea in people by at least 30 percent.
Affecting around 1.5 million adults in the UK, sleep apnea is a condition where the upper airway from the back of the nose to the throat closes repetitively during sleep, restricting oxygen intake and causing people to wake as often as 100 times or more per hour.
Those with untreated sleep apnea are more likely to develop cardiovascular disease, dementia and depression, and are two to four times more likely to crash a car than the general population.
Despite almost thirty years of research, there are no approved drug therapies to treat the condition.
Professor Danny Eckert, Principal Research Scientist at NeuRA and Professor and Director of Adelaide Institute for Sleep Health at Flinders University, has brought scientists one step closer by repurposing two existing medications to test their efficacy in people in sleep apnea.
Previous research showed two classes of medication, reboxetine and butylbromide, were able to keep muscles active during sleep in people without sleep apnoea, and assist their ability to breathe.
By repurposing the medications, researchers used a multitude of recording instruments to measure whether reboxetine and butylbromide could successfully target the main causes of sleep apnoea.
This included balancing the electrical activity of muscles around the airway, preventing the throat from collapsing while people were sleeping, and improving the regulation of carbon dioxide and breathing during sleep.
Results from the study showed these medications did in fact increase the muscle activity around participants’ airways, with the drugs reducing the severity of participants’ sleep apnoea by up to one third.
Almost everyone we studied had some improvement in sleep apnoea. People’s oxygen intake improved, their number of breathing stoppages was a third or more.
These new findings allow researchers to further refine these types of medications so that they have even greater benefit than what has currently been found.
Commenting on the study, Professor Eckert said:
“We were thrilled because the current treatment options for people with sleep apnoea are limited and can be a painful journey for many,” he said. Next, we will look at the effects of these and similar medications over the longer term. We will assess whether we can harness the benefits of one drug without needing to use them both.”
“Equally, we will test whether these treatments can be combined with other existing medications to see if we can improve their efficacy even more,” he continued.
Until now, the main therapy for sleep apnoea involves wearing a mask to bed, or Continuous Positive Airway Pressure Therapy (CPAP), which benefits millions. However, many people find it uncomfortable and half the people that try it find it hard to tolerate.
Plus, the efficacy of second line therapies, such as mouthguards fitted by dentists, can be unpredictable and expensive.
Funding: This study was funded by the National Health and Medical Research Council of Australia.
The noradrenergic agent reboxetine plus antimuscarinic hyoscine butylbromide reduces sleep apnoea severity: A double-blind, placebo-controlled, randomised crossover trial
The noradrenergic agent reboxetine combined with the anti-muscarinic hyoscine butylbromide has recently been shown to improve upper airway function during sleep in healthy individuals. However, the effects of this drug combination on obstructive sleep apnoea (OSA) severity are unknown.
Accordingly, this study aimed to determine if reboxetine plus hyoscine butylbromide reduces OSA severity. Secondary aims were to investigate the effects on key upper-airway physiology and endotypic traits. 12 people with OSA aged 52±13 years, BMI = 30±5 kg/m2 completed a double-blind, randomised, placebo-controlled, cross-over trial (ACTRN12617001326381). Two in-laboratory sleep studies with nasal mask, pneumotachograph, epiglottic pressure sensor and bipolar fine-wire electrodes into genioglossus and tensor palatini muscles were performed separated by approximately 1-week.
Each participant received either reboxetine (4mg) plus hyoscine butylbromide (20mg), or placebo immediately prior to sleep. Polysomnography, upper-airway physiology and endotypic estimates of OSA were compared between conditions. Reboxetine plus hyoscine butylbromide reduced the apnoea/hypopnoea index by (mean±SD) 17±17 events/h from 51±30 to 33±22 events/h (p = 0.005) and nadir oxygen saturation increased by 6±5% from 82±5 to 88±2% (p = 0.002).
The drug combination increased tonic genioglossus muscle responsiveness during non-REM sleep (median [25th, 75th centiles]: -0.007[-0.0004, -0.07] vs. -0.12[-0.02, -0.40] %maxEMG/cmH2O, p = 0.02), lowered loop gain (0.43±0.06 vs. 0.39±0.07, p = 0.01), and improved airway collapsibility (90[69, 95] vs. 93[88, 96] %eupnea, p = 0.02), without changing the arousal threshold (p = 0.39).
These findings highlight the important role that noradrenergic and muscarinic processes have on upper airway function during sleep and the potential for pharmacotherapy to target these mechanisms to treat OSA.