Obstructive Sleep Apnea

Overview

Obstructive sleep apnea (OSA) is a condition characterized by multiple episodes of sleep-related  apnea or hypopnea (loss or decrease in breathing) during sleep, resulting in symptoms such as   snoring, snorting/gasping, or breathing pauses during sleep; and daytime sleepiness, fatigue, or unrefreshing sleep despite sufficient opportunities to sleep.  It occurs in a significant number of people and is associated with major health risks.  Along with an increased risk of drowsy driving and motor vehicle accidents, there is a higher rate of hypertension, stroke, coronary artery disease, insulin resistance, type 2 diabetes mellitus, and perioperative complications.  Individuals with OSA have a 2- to 3-fold increased risk of all-cause mortality compared with those who do not have OSA. 1

Now, recent studies show that OSA and Major Depressive Disorder also tend to co-occur. A 4-year study with controls, run by Peppard and colleagues that included 1400 community-dwelling patients revealed a 2-fold increase in depression with mild OSA and a 2.6-fold increase in depression with moderate to severe OSA.

A large national study by Wheaton and associates 3 showed a high association of sleep apnea and an elevated Patient Health Questionnaire-9 (PHQ-9) score of more than 10 (indicative of moderate depression) with over double of the normal risk.

The prevalence of OSA in the general population differs by age and gender. In men aged 30 to 49 years, the prevalence is 10%; in older men (aged 50 to 70), it is 17% among the general population. The prevalence in women aged 30 to 49 is 3%, and in women aged 50 to 70 it is 9%. 4 it is estimated that 82% of men and 92% of women with moderate-to-severe sleep apnoea have not been diagnosed. 5

The reasons for the co-occurrence of OSA and MDD is not well established. Possible reasons are the fragmentation of sleep, low oxygen states, and disruption of the sleep-wake cycle. It has also been hypothesized that depression may exacerbate or impede recovery of the neuronal injury caused by OSA, specifically in sensitive brain regions responsible for affect and cognition.6 There may also be confounding risks or root causes for both MDD and OSA. These include age, gender, obesity, hypertension, diabetes, and cerebrovascular disease.

There are also neurotransmitters for both sleep and mood regulation, such as serotonin, dopamine, norepinephrine, and g-aminobutyric acid. Serotonin in particular is interesting given its role in depression and also the fact that it influences the strength of muscles in the upper airway that contribute to OSA and plays an important role in causing arousals from sleep.7

Diagnosis

In a general clinical setting, the diagnoses of OSA and MDD can be difficult to diagnose and differentiate from each other due to overlapping symptoms.  Symptoms and signs suggestive of OSA, such as snoring, insomnia, unrefreshing sleep, and excessive daytime sleepiness are often present. In general, patients with comorbid depression tend to report more sleepiness, which is also evidenced by higher Epworth Sleepiness Scale scores.8 A diagnostic polysomnograph (overnight sleep study) is necessary to complete the diagnosis.

Psychological scales that can effectively be used to screen for OSA are the STOP Bang9 questions or the Berlin Questionnaire.10

Treatment

Once the patient completes the PSG, the information from it can be empowering.  It indicates the amount of time spent in a low or zero breathing (apnea-hyponea index), the lowest oxygen saturation during the course of the night, the loudness of snoring, the presence of REM sleep, and periodic limb movements.

The treatment of choice for OSA is positive airway pressure (PAP) therapy, including continuous positive airway pressure (CPAP), bi-level PAP (BPAP), or auto-PAP (APAP). For those who are unable to tolerate PAP therapy, alternative treatments—such as a mandibular advancement device, upper airway surgery, or hypoglossal nerve stimulation therapy—might be considered. Improvement in depressive symptoms has been reported after the treatment of OSA.11-14

CPAP delivers a constant pressure based on a pressure titration study. The pressure keeps the airway open as a pressure column. BPAP delivers 2 different levels of pressure—one for inspiration and the other for expiration (IPAP and EPAP). With APAP the machine can automatically adjust the pressure slowly within a prescribed range based on the patient’s need.

The mandibular advancement device is an oral device that the patient wears inside of the mouth while asleep. This device pulls the mandible forward and opens up the airway in the back of the tongue. Hypoglossal nerve stimulation therapy uses an implanted device to stimulate cranial nerve XII (the hypoglossal nerve); the result is tongue protrusion, which opens up the airway in the back of the tongue as well.  Improvement in depressive symptoms has been reported after the treatment of OSA.8,14-16

References

  1. Young T, Palta M, Dempsey J, et al. Burden of sleep apnea: rationale, design, and major findings of the Wisconsin Sleep Cohort study. WMJ. 2009;108:246-249.
  2. Peppard PE, Szklo-Coxe M, Hla KM, Young T. Longitudinal association of sleep-related breathing disorder and depression. Arch Intern Med. 2006;166:1709-1715.
  3. Wheaton AG, Perry GS, Chapman DP, Croft JB. Sleep disordered breathing and depression among U.S. adults: National Health and Nutrition Examination Survey, 2005-2008. Sleep. 2012;35:461-467.
  4. Peppard PE, Young T, Barnet JH, et al. Increased prevalence of sleep-disordered breathing in adults. Am J Epidemiol. 2013;177:1006-1014.
  5. Ancoli-Israel S, Kripke DF, Klauber MR, et al. Sleep-disordered breathing in community-dwelling elderly. Sleep. 1991;14:486–95.
  6. Cross RL, Kumar R, Macey PM, et al. Neural alterations and depressive symptoms in obstructive sleep apnea patients. Sleep. 2008;31:1103-1109.
  7. Buchanan GF, Smith HR, Macaskill A, Richerson GB. 5-HT2A receptor activation is necessary for CO2-induced arousal. J Neurophysiol. 2015;114:233-243.
  8. Ishman SL, Cavey RM, Mettel TL, Gourin CG. Depression, sleepiness, and disease severity in patients with obstructive sleep apnea. Laryngoscope. 2010;120:2331-2335.)
  9. Farney RJ, Walker BS, Farney RM, et al. The STOP-Bang equivalent model and prediction of severity of obstructive sleep apnea: relationship to polysomnographic measurements of the apnea/hypopnea index. J Clin Sleep Med. 2011;7:459-465.
  10. Netzer NC, Stoohs RA, Netzer CM, et al. Using the Berlin Questionnaire to identify patients at risk for the sleep apnea syndrome. Ann Intern Med. 1999;131:485-491.
  11. Chung F, Yegneswaran B, Liao P, et al. STOP questionnaire: a tool to screen patients for obstructive sleep apnea. Anesthesiology. 2008;108:812–21.
  12. Chung F, Yegneswaran B, Liao P, et al. Validation of the Berlin questionnaire and American Society of Anesthesiologists checklist as screening tools for obstructive sleep apnea in surgical patients. Anesthesiology. 2008;108:822–30..
  13. Finkel KJ, Searleman AC, Tymkew H, et al. Prevalence of undiagnosed obstructive sleep apnea among adult surgical patients in an academic medical center. Sleep Med. 2009;10:753–8.
  14. Habukawa M, Uchimura N, Kakuma T, et al. Effect of CPAP treatment on residual depressive symptoms in patients with major depression and coexisting sleep apnea: contribution of daytime sleepiness to residual depressive symptoms. Sleep Med. 2010;11:552-557.
  15. Povitz M, Bolo CE, Heitman SJ, et al. Effect of treatment of obstructive sleep apnea on depressive symptoms: systematic review and meta-analysis. PLoS Med. 2014;11:e1001762.
  16. Ejaz SM, Khawaja IS, Bhatia S, Hurwitz TD. Obstructive sleep apnea and depression: a review. Innov Clin Neurosci. 2011;8:17-25.