Combined Medications Show Promise for Sleep Apnea Treatment

By Admin

New research on combined medications has shown reductions in sleep apnea symptoms as high as 30 percent. The medications, called reboxetine and hyoscine butylbromide, have been studied in the past for their combined effects on sleep-related breathing. Reboxetine, a type of drug called a noradrenergic, is used on its own to treat depression, while hyoscine butylbromide is an antispasmodic used to calm muscles and reduce cramps. For the study, the two drugs were repurposed to treat sleep apnea, which helped to keep muscles active during sleep and sustain regular breathing patterns. While previous studies found similar improvements in upper airway functioning when using this combination of drugs, current research has focused primarily on the reduction of sleep apnea symptoms, particularly for obstructive sleep apnea (OSA). These findings have further emphasized the importance of these vital autonomic systems for upper airway stability and breathing, and further research is expected.

While medications for sleep apnea have been extremely limited up to this point, research in this area is revealing new possibilities for improved pharmacological approaches in the future, either for use as a primary treatment option or as a complementary treatment used along with CPAP therapy.

Drug Mechanisms

While reboxetine and hyoscine butylbromide are different classes of drugs, both contribute to autonomic processes that regularize breathing and inhibit upper airway collapsibility. On one hand, reboxetine acts as a noradrenaline (also called norepinephrine) reuptake inhibitor (NaRI), which increases the amount of noradrenaline in the body by blocking reuptake after each synapse. Since noradrenaline stimulates the nervous system and increases blood flow to the peripheries, it can have a direct effect on respiration stability. Similarly, hyoscine butylbromide acts as an anticholinergic (antispasmodic), which blocks a transmitter called acetylcholine from stimulating nerves and muscles that control autonomic systems such as digestion and respiration. The balance achieved by the combined effects of the two drugs allowed for improvements in several areas, including reduction of the apnea/hypopnoea index (AHI) by 30 percent, an increase of oxygen saturation 6 percent, an increase in upper-airway muscle responsiveness, and improved airway collapsibility.

According to the head of research, Professor Danny Eckert, who works as the Principal Research Scientist at the Neuroscience Research Australia and Director of Adelaide Institute for Sleep Health at Flinders University, the study is just the beginning of the research planned for these types of drug combinations.

“Almost everyone we studied had some improvement,” Professor Eckert 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...and we will test whether these treatments can be combined with other existing medications to see if we can improve their efficacy even more.”

Study Description

Published in the Journal of Physiology, the full title of the study is “The noradrenergic agent reboxetine plus the antimuscarinic hyoscine butylbromide reduces sleep apnoea severity: a double-blind, placebo-controlled, randomised crossover trial.” As its description states, the study aimed to determine if the drugs in question could be combined at measured dosages to control airway collapse and induce healthy breathing in OSA patients. In addition, there were secondary aims to investigate the effects on specific airway functions and endotypic traits.

A total of 12 people with OSA aged between 40 and 65 years completed a double-blind, randomi\zed, placebo-controlled, trial. This means that neither the participants nor the experimenters knew who received the drugs and who received the placebo. To assess the results, in-laboratory sleep studies with complete polysomnography measures (i.e. nasal masks, epiglottic pressure sensors, fine-wire electrodes, etc.) were taken. The drug dosages used were 4 mg for reboxetine and 20 mg for hyoscine butylbromide, taken immediately prior to sleep.

Limitations

Currently, the drugs reboxetine and hyoscine butylbromide are not being prescribed to treat sleep apnea. The research on this drug combination is for experimental purposes only and further studies will need to be conducted in order to assess the full effects of the drugs on OSA symptoms. While a 30 percent reduction in primary symptoms is clinically relevant, the study authors state in their conclusion that it is yet uncertain how these findings can translate to clinically relevant treatments for the OSA-patient population.

It should also be noted that reboxetine is not approved for use in the United States at this time, and has yet to pass clinical trials required by the FDA. While the drug is approved for use in Europe and other countries, it is prescribed primarily for depression, ADHD, and other mental conditions associated with norepinephrine levels in the brain.

Another issue involved with drug combinations is the existence of potential side effects for each drug, as well as additional effects made possible by the combination of drug properties.

According to information available on Patient.Info.com, possible side effects for reboxetine and hyoscine butylbromide are as follows:

Insomnia
Dizziness
Dry mouth
Constipation
Nausea
Sweating

In addition, previous studies found that the combination of reboxetine and hyoscine butylbromide can reduce REM sleep, which is extremely important for both sleep and daily functioning. While research has focused mainly on the potential benefits of the drug combination, such limitations should be noted as a consideration for future research.

Key Takeaway

The primary focus of this research was on the noradrenergic and muscarinic processes that are key mechanisms in upper airway muscle control during sleep. Not only do these findings outline the important roles that these noradrenergic and muscarinic processes have on sleep-related breathing, but they also highlight the potential for pharmacotherapy to target these kinds of specific mechanisms to treat sleep-related breathing disorders more accurately.

These findings represent a breakthrough moment in the establishment of possible pharmacological treatments for sleep apnea, which could be a great help to those with persistent symptoms or those who have difficulties with PAP-therapy adherence, a common focus area for both patients and providers wishing to improve sleep apnea treatment throughout the country and world.