PAP or Pill? Pharmaceutical Alternatives to Sleep Apnea

Would you rather wear positive airway pressure (PAP) therapy each night or take a pill before bed? For most, it would seem they would love to choose the latter option as PAP machines can be viewed as burdensome. Wearing a mask to bed has long been an issue for many sleep apnea sufferers who are seeking a better night of sleep. As sleep apnea treatment continues to evolve, there is a growing population of patients interested in taking a pill before bed and not worrying about wearing a mask throughout the night. However, is it worth throwing out the mask and taking the chance that a pill can be as effective as the tried-and-true PAP machine?

The current gold standard of treatment for obstructive sleep apnea (OSA) is PAP therapy. The most commonly prescribed PAP device used to treat straightforward OSA, in patients without additional factors like chronic respiratory failure or central sleep apnea (CSA), is continuous positive airway pressure, or CPAP. This approach to OSA treats the underlying mechanisms of sleep apnea by providing an airway shunt with each breath, allowing optimal airflow and eliminating the nocturnal hypoxic effects of airway closure. Compliance with CPAP has been shown to eliminate OSA and hypoxemia caused by nocturnal airway closure, as well as reduce secondary negative effects of chronic hypoxemia on endocrine and cardiopulmonary systems. The downside to using a PAP device is that it must be worn each night - one-time use is not a cure. The average national compliance for PAP use in the clinical setting is only between 30%-60%.¹ Many people dislike wearing a mask to bed, finding it to be uncomfortable and cumbersome in new social scenarios, especially when the patient begins to co-sleep with a partner.

As OSA treatments continue to evolve, a new alternative treatment has arisen - a pharmaceutical approach, which includes a handful of options, such as selective serotonin reuptake inhibitors (SSRIs), tricyclic anti-depressants, acetazolamide, medroxyprogesterone and the more recent dopamine/ norepinephrine reuptake inhibitor (DNRI), Solriamfetol.² Each of these medications are primarily prescribed by medical providers for a conventional purpose other than treating OSA.³

SSRIs are conventionally prescribed as anti-depressant medications that are considered non-stimulating. Protryptyline in particular is a tricyclic anti-depressant drug increasingly thought to have a positive effect on breathing at night. In relation to improvement of OSA as a secondary effect, it is thought the improvement in patients' excessive daytime sleepiness occurs by means of suppressing rapid eye movement (REM) sleep and shortening the time spent in the most severe period of OSA expression with the lowest oxygenation.⁴

There is also the very mild stimulating effect of SSRI's with a serotonin increase that could provide enough upper airway nerve stimulation to maintain airway compliance. The findings being observed in the laboratory setting include an increase in blood flow and volume in association with increased upper airway tone for patients taking SSRIs that also express sleep apnea. The effect is considered incomplete and SSRIs should not be seen as a primary approach for the treatment of OSA at this time.

Acetazolamide, a carbonic anhydrase inhibitor, is typically prescribed to reduce the effects of damage to the heart by increasing ventilation via metabolic acidosis. Increasing metabolic acidosis also increases the ventilatory drive, thereby increasing the patient's respiratory rate. The increased ventilatory drive is thought to be the reason behind the reduction of severity in CSA, otherwise known as the "other type of apnea." In CSA, there is an absence of respiratory effort and a pause in airflow and breathing, which can result in a decrease in minute ventilation. For many reasons, some patients with CSA are observed to have periodic breathing where they are no longer breathing in a stable pattern and the airflow and effort channels show intermittent waxing and waning for multiple rounds of periodicity during an overnight in-lab polysomnography study (PSG). The increased ventilation that occurs when taking acetazolamide however has been shown to change CSA to OSA.⁵ The transference of apneas from central to obstructive appears to occur due to an increased respiratory drive however, there is no additional stimulation to maintain upper airway tone to eliminate obstruction.

This approach to improvement in sleep pathology is a positive step that supports the conventional purpose for the prescription of the medication - cardiac improvement via reduction in retaining carbon dioxide.⁶ However, the switch from central to obstructive apnea does not resolve pathologic breathing and leaves much room for treatment still needed.

Medroxyprogesterone is an estrogen hormonal replacement therapeutic and has been observed to reduce the effects of obesity hypoventilation syndrome. The increased ventilation has also not been seen as effective on treating obstructive apneas. The best improvement is in the patient population using hormonal therapy that express a combination of hypercapnic hypoxemia and OSA.⁷

Solriamfetol, a DNRI recently found to improve daytime OSA symptoms, is used to decrease daytime fatigue and excessive tiredness in the narcoleptic population. However, it can improve excessive daytime sleepiness in patients with OSA that are also being treated with CPAP. It is important to note that this class of medication is used to increase daytime wakefulness and not to correct the underlying obstruction of the airway when sleeping.⁸

These medications are among a handful of the others in the same pharmaceutical classes that can be used for similar approaches; however, they all have something in common. They affect OSA in a manner only to be considered as a minor improvement and not as a primary approach to the treatment of OSA. The gold standard treatment for OSA is CPAP, which is still the leading line of defense to resolve the core mechanisms of nocturnal airway collapse. These medications are possible new steps to take in the overall treatment plan, especially for those who struggle with CPAP compliance.

References

1. Rotenberg BW, Murariu D, Pang KP. Trends in CPAP adherence over twenty years of data collection: a flattened curve. J Otolaryngol Head Neck Surg. 2016;45(1):43. doi:10.1186/s40463-016-0156-0
2. Solriamfetol (Rx). Retrieved from https://reference.medscape.com/drug/sunosisolriamfetol-1000266
3. Mayo Clinic. Fluoxetine (Oral Route). Retrieved from https://www.mayoclinic.org/drugssupplements/fluoxetine-oral-route/precautions/drg20063952
4. Medline Plus. Protriptyline. Retrieved from https://medlineplus.gov/druginfo/meds/a604025.html
5. Medline Plus. Acetazolamide. Retrieved from https://medlineplus.gov/druginfo/meds/a682756.html#:~:text=Acetazolamide%20is%20used%20to%20treat,the%20pressure%20in%20the%20eye
6. Saunders NA, Sullivan CE. Sleep and Breathing (Lung Biology in Health and Disease). 1994;71:405-448. Published by Marcel Dekker Inc
7. com. Medroxyprogesterone. Retrieved from https://www.drugs.com/medroxyprogesterone.html#:~:text=Medroxyprogesterone%20is%20a%20progestin%20(a,periods%2C%20or%20abnormal%20uterine%20bleeding
8. Obstructive Sleep Apnea (OSA) Medication. Retrieved from https://emedicine.medscape.com/article/295807-medication