Researchers have found a combination of drugs that may help ease severe sleep apnea symptoms.
Sleep apnea causes you to stop breathing briefly dozens of times every night. It is a serious condition that causes daytime fatigue, high blood pressure, and heart problems. Having sleep apnea also increases your risk of insulin resistance, also known as type 2 diabetes. If you are unable to sleep well, you may develop metabolic syndrome, which causes high blood pressure, abnormal cholesterol levels, high blood sugar, and increased waist circumference. Liver problems, complications with medications and surgery, plus sleep deprived partners are also complications of sleep apnea.
Daytime sleepiness is an irritating problem in and of itself, and 13% of men and 6% of women, ages 30 to 70, who are sleep-deprived carry a very high risk for depression, cognitive impairment, and premature death.
What is the answer for sleep apnea?
Studies, clinical trials, lab experiments, and research have eluded scientists who have looked for drugs to ease obstructive sleep apnea symptoms. However, Boston researchers have found a combination of medications that have been used for other conditions. These medications seem to work while asleep to stimulate the muscles in the upper airway.
In a study of 20 patients, scientists used atomoxetine and oxybutynin in a pill to study the effects of these medications on sleep apnea. The study discovered that when taken together these two drugs helped prevent the patients' airways from being obstructed.
The apnea-hypopnea index (AHI) was changed from a median of 28.5 hourly obstructions to 7.5 with the pills. It was noted that 15 patients with the highest AHIs had a reduction of 74% and the other patients experienced at least a 50% reduction in apneas. The research also reported that blood oxygenation improved, too. These results were reported at the European Respiratory Society’s International Congress in Paris amid resounding cheers and congratulations.
Sigrid Veasey of the University of Pennsylvania (UPenn), a physician-researcher, says, “We’ve never had a drug combination, or any sort of a drug, that consistently improved everybody’s AHI. That’s actually unbelievably exciting.” Martina Mason, a sleep physician at the Royal Papworth Hospital in Cambridge, U.K., who co-authored a 2013 review of 30 previous, underwhelming drug trials, adds that it’s “a great first step.”
Dr. Wellman, a physician who has studied sleep apnea since 2001, began testing different drugs on sleep apnea, but nothing seemed to work. Then in 2015, a post-doc student knocked on his lab door. Wellman let him trial a drug combination that had been used on animals in different labs. Wellman wasn’t happy about these tests, but then data proving the safety and success started to arrive
Atomoxetine and Oxybutynin
The first drug, atomoxetine, was approved by the FDA in 2002 to treat Attention Deficit Hyperactivity Disorder (ADHD). The drug works by increasing the messaging in the brain by stimulating neurotransmitter norepinephrine. The levels of this neurotransmitter are generally reduced during sleep. Giving a stimulating drug to patients at bedtime seemed counterproductive, but it worked.
Richard Horner, who works as a sleep physiologist, injected rats with a norepinephrine-mimicking medication where the brainstem controls the hypoglossal nerve, which regulates the upper airway muscles. The drug significantly improved the activity of the large tongue muscles that keep the tongue down and the throat open. The drug was effective during non-rapid eye movement sleep, but not during REM sleep. Dr. Horner knew that another drug was needed to work during REM sleep.
The second drug, oxybutynin, improves the large tongue muscle responsiveness during REM sleep. More trials are ongoing to see if the drug reduces subconscious arousals and improves sleep quality. The combination of these two drugs worked in lab experiments.
Apnimed, Inc., a new Cambridge, Massachusetts company, formed to commercialize the discovery and recently received $25 million from Morningside Venture Capital in Newton, Massachusetts. These funds were granted to fund a plan to undertake Phase II trials, involving more than 100 patients. The study will determine the dosing ranges, plus any side effects.
Researchers and sleep physicians believe that some side effects might be unrelated to breathing, and may make the drug combination unusable for some sleep apnea patients. Those who are at risk for hypertension and heart attacks, the stimulant effect of oxybutynin may be prohibitive. Oxybutynin also effects the bladder muscles, which may prove challenging for someone with sleep apnea.
As exciting as this finding is, there are still problems. The drug combination reduced AHIs, but the number of subtle awakenings that leave patients exhausted stayed high. However, if the combination of these two drugs proves to be effective and safe in larger trials, it might free many sleep apnea patients from the unwieldy continuous positive airway pressure or CPAP machines. These machines blow air into the throat to keep the airway open. CPAP machines require users to wear uncomfortable masks and headgear at night.
Searching for sleep apnea treatments that are not as invasive as CPAP machines has been ongoing for years. The noncompliance of users with CPAP machines has been documented, and these users are at risk for long-term dangers. Something easier to use, like pills, needs to be found as soon as possible.
Even with the potential of medications being available for sleep apnea, it is essential to use your CPAP machine. These medications are still being tested and need FDA approval for use for sleep apnea. It could be years before your doctor can prescribe oxybutynin and atomoxetine for sleep apnea.
Your CPAP machine isn’t so bad; you will sleep more comfortable and healthier if you use your prescribed machine. Don’t worry that you are tied to a noisy device all night with tubes, masks, and straps hindering your movement. There are different types of CPAP machines available and much easier to get used to than CPAP devices from years ago.
If the mask you use is sealed, and the air pressure from the tube stays constant, your CPAP is very efficient. Try out different types to see what is most comfortable for you and what straps are best to hold your mask in place. You will need to try out a few before you find the one you are satisfied with, but the CPAP machine can save your life.