As our understanding of the interrelationship between sleep and depression grows, it is becoming clear that treatment of one may help the other.
Depression as a whole for all age groups is one of the most prevalent and costly disorders in the United States.1 The direct and indirect costs of depression have been estimated at $43 billion each year, not including pain and suffering and diminished quality of life.2 Because the prevalence of depression and associated comorbidities is very high among working-age persons, up to 60% of the societal costs of depression are believed to be due to workplace costs.3
Depression affects as many as 12% of men and 25% of women at some point in their life; the estimated overall lifetime prevalence of depression in the United States is roughly 17%.4-6 Significant depressive symptoms are seen in nearly 40% of all medically ill patients.7 Those with stroke, dementia, diabetes, heart disease, and renal impairment have especially high rates of depression.8-12 The risk of developing major depression spans across ethnicity, education, income levels, and marital status, and persons of all ages may be affected.4 At any given time, about 6 million Americans suffer from depression.13 Furthermore, depression is one of the most frequent reasons for primary care visits.6
The correlation between sleep quality and depression is an important issue, and one that is growing in recognition. More than 80% of people with depression experience sleep disturbances, such as early morning waking or frequent awakenings throughout the whole night.14 Even in chronic low-grade depression, which affects roughly 3% of people, insomnia and/or sleepiness may be the most prominent symptom.15
Depression may be associated with other medical problems, including Alzheimer’s disease, cancer, chronic pain, diabetes, heart disease, human immunodeficiency virus (HIV) infection, stroke, and Parkinson’s disease (see Table 1, page 40).16,17 Despite these associations, however, it is important to view depression as a separate and treatable condition; hence, once any comorbid medical conditions have been identified and treated, teasing apart the possible causes for a patient’s depression may not be as useful as simply understanding that a comorbidity exists and treating the depression. The distinction between so-called endogenous depression and depression that is considered reactive is, for practical purposes, irrelevant. Depression can affect a patient’s prognosis and ability to adhere to treatment for other medical problems; hence, depression and associated comorbidities should be addressed carefully and managed appropriately.
Depression may also coexist with a number of other psychiatric disorders, such as anxiety and substance abuse. It is not always possible to make a precise diagnosis, particularly in practices in which patients are often seen at an early stage of illness; however, when possible, the physician should differentiate between depression and another psychiatric disorder, because doing so may make it easier to determine the prognosis and to provide effective management.
|Table 1. Conditions associated with an increased incidence of depressive symptoms.16,17|
Sleep Disorders and Depression
Sleep disorders associated with depression generally fall into one of two categories—sleep apnea and insomnia.
The results of a recent study show the interrelationship between depression and sleep apnea. A cross-sectional survey involving almost 19,000 randomly selected persons aged 15 to 100 years was carried out between 1994 and 1999.18 The questionnaire included a series of questions about sleep quality, breathing-related sleep disorder symptoms, mental disorders, and medical conditions. Just over 2% of the people surveyed were found to have OSA at the time of the interview, and 2.5% had some other type of breathing-related sleep disorder. As many as 18% of people with a major depressive disorder diagnosis also had a breathing-related sleep disorders diagnosis, and roughly 18% of people with a breathing-related sleep disorders diagnosis had a major depressive disorder diagnosis. Multivariate models showed that even after controlling for factors such as obesity and hypertension, the odds of having a breathing-related sleep disorders diagnosis was 5.26 for individuals with a major depressive disorder diagnosis. The investigators of this study—the first to show the strength of the link between the two disorders—concluded that the identification of either depression or a breathing-related sleep disorder should prompt the investigation of the other disorder, because nearly one fifth of people with one disorder also have the other disorder.
Insomnia can be treated with the use of drugs, behavioral therapy, or a combination of both. If depression has been determined to be an underlying cause of insomnia, then treatment of the depression may have a beneficial effect on the insomnia. If drug therapy is required for the treatment of insomnia, there are a number of over-the-counter and prescription products available. Behavioral approaches to the treatment of insomnia include:
• Stimulus control treatment (retraining the person with insomnia to associate the bed and bedroom with rapid sleep onset)
• Relaxation techniques
• Paradoxical intention treatment (persuading the person with insomnia to engage in the most feared behavior, which to that person is staying awake)
• Sleep restriction treatment (similar to paradoxical intention treatment, sleep restriction treatment uses a paradoxical approach in which less time is spent in bed; the idea is to create a mild state of sleep deprivation that will eventually cause a more rapid sleep onset, more efficient sleep, and consis- tent sleep duration);
• Cognitive behavioral treatment (the use of cognitive behavioral therapy combined with other behavioral treatments to help change incorrect beliefs and attitudes about sleep)
• Sleep hygiene education (educating the patient about health practices such as diet, exercise, substance use, and environmental factors such as light, noise, and temperature that can be positive or negative for one’s sleep).
Insomnia may occur as a result of depression, or may lead to depressive symptoms. Insomnia is associated with significant impairments in quality of life, and insomnia sufferers are more likely to be depressed than those who have good sleep.19 Although the association between insomnia and depression has long been recognized, the issue remains a question of which comes first—”the chicken or the egg?”
In order to address this issue, investigators performed a study to determine whether treating insomnia successfully without medication can cause depression to lift as well.20 A study sample consisting of 86 consecutive patients who presented as suffering from chronic insomnia was established. Two thirds of this sample were people who were also suffering from depression. During an initial hour-long interview, self-report estimates of key sleep parameters were recorded, and a depression questionnaire was administered. The subjects then used a “Sleep Better Without Drugs” self-help program (a book and three audio cassettes) at home to improve their sleep. At follow-up 6 to 8 weeks later, the sleep parameters were recorded again, and the depression questionnaire was administered again. For a person’s sleep to be classified as having “improved significantly,” that person must have fulfilled one or more of the following criteria: a reduction of at least 2 hours in the time taken to fall asleep; an increase of at least 2 hours in total sleep time during the night; a reduction of at least eight in the number of awakenings during the night; or elimination of usage of sleeping medication, with no deterioration in key sleep parameters. Using these strict criteria, 87% of all subjects were sleeping significantly better at follow-up. The key finding of the study was that 70% of the insomnia sufferers who were depressed before treatment and learned to sleep significantly better were no longer depressed, or were significantly less depressed, once their sleep had improved. In contrast, among people who did not learn to sleep significantly better, none experienced a significant reduction in depression.
Management of Sleep Apnea
Nonsurgical approaches to the management of OSA include behavioral modification, drug therapy, and use of mechanical devices. Behavioral modifications include avoidance of alcohol and sedative medications, alteration of sleep position, avoidance of sleep deprivation, and weight loss. Drug therapy for OSA is of limited clinical value, with the exception of thyroxine replacement in patients with hypothyroidism.
Nasal CPAP is the initial treatment of choice for OSA in adults and can reduce mortality associated with OSA.21 CPAP allows progressive restoration of air flow, as the pressure applied exceeds the airway opening pressure. Appropriate CPAP can resolve OSA in many patients. It works by pneumatically splinting the collapsible upper airway. Although effective, CPAP is uncomfortable or intolerable for some patients, and variable patient compliance remains a significant problem. Studies have found that up to 25% of patients discontinue CPAP therapy.22,23
There are also surgical options for the management of severe OSA. Tracheostomy was the initial surgical procedure performed for OSA and is effective in decreasing the morbidity and mortality of the disorder. Because tracheostomy bypasses the collapsible upper airway, it is the definitive surgical treatment for OSA. This procedure, however, is associated with complications and significant emotional and physical morbidity. From the patient’s perspective, tracheostomy is aesthetically and socially undesirable. Nevertheless, tracheostomy remains an important surgical option in patients with severe OSA who cannot tolerate CPAP, and for whom other interventions are ineffective or unacceptable.
Uvulopalatopharyngoplasty (UPPP) is currently the most commonly performed surgical procedure for the treatment of OSA. UPPP is a procedure that enlarges the retropalatal upper airway by excising a portion of the posterior soft palate and uvula with trimming and reorientation of the tonsillar pillars. The tonsils, if present, are excised as well. Historically, UPPP has been considered effective in about 50% of patients with OSA.24 These suboptimal results are due largely to unresolved obstruction of the upper airway in sites other than the retropalatal region. Preoperative screening studies are now used to identify patients in whom the retropalate is the primary site of obstruction and in whom UPPP is more likely to be effective. Significant weight gain after UPPP may also contribute to suboptimal results.
Laser-assisted uvulopalatoplasty (LAUP) has been developed for the treatment of snoring and OSA. It is performed under local anesthesia on an outpatient basis. LAUP is a multistaged procedure that involves carbon dioxide laser excision of the uvula and a small portion of the soft palate at each stage. The goal of staging is to excise the least amount of palatal tissue needed to reduce snoring effectively while reducing the risk of velopharyngeal insufficiency. LAUP has been reported to reduce morbidity, such as pain and bleeding, as compared to traditional UPPP. LAUP is also less expensive and requires less time off from work.
Additional surgical procedures used in selected patients with severe OSA, all of which are designed to enlarge the retropalatal airway, include uvulopalatopharyngoglossoplasty; linguoplasty; laser midline glossectomy; inferior sagittal mandibular osteotomy and genioglossal advancement with hyoid myotomy and suspension (GAHM); and maxillomandibular osteotomy (MMO). Laser midline glossectomy involves laser extirpation of a portion of the posterior midline tongue. Laser lingual tonsillectomy, reduction of the aryepiglottic folds, and partial epiglottectomy may be performed in selected patients. Linguoplasty involves additional extirpation of posterior and lateral tongue tissue. In GAHM, the glenoid tubercle of the mandible (the anterior attachment of the tongue) is advanced by a limited osteotomy of the mandible. MMO enlarges the retrolingual airway maximally and provides some enlargement of the retropalatal airway as well. The major drawback of MMO is that it is a complex procedure limited to only a few institutions, and is associated with significant postoperative morbidity.
It is well established that depression can lead to insomnia. New research indicates that the reverse is also true—that having chronic insomnia can lead to depression. For patients who suffer from both depression and chronic insomnia, treating the insomnia successfully may eliminate or significantly reduce the depression.
If symptoms of depression occur in a patient with a known sleep disturbance, appropriate treatment may require looking at both the treatment for the sleep disturbance and the possibility that the patient has a depressive disorder.
1. Hirschfeld RM, Keller MB, Panico S, et al. The National Depressive and Manic-Depressive Association consensus statement on the undertreatment of depression. JAMA. 1997;277:333-340.
2. Finkelstein SN, Berndt ER, Greenberg PE. Economics of depression: a summary and review. Presented at: the National Depressive and Manic-Depressive Association sponsored Consensus Conference on the Undertreatment of Depression; January 17-18, 1996; Washington, DC.
3. Birnbaum HG, Barton M, Greenberg PE, et al. Direct and indirect costs of rheumatoid arthritis to an employer. J Occup Environ Med. 2000;42:588-596.
4. Pincus HA, Pettit AR. The societal costs of chronic major depression. J Clin Psychiatry. 2001;62:S5-S9.
5. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Text Revision. Washington, DC: American Psychiatric Association; 2000.
6. Way K, Young CH, Opland E, Whitehouse D, Hughes T. Antidepressant utilization patterns in a national managed care organization. Drug Benefit Trends. 1999;11:6BH-11BH.
7. Agency for Health Care Policy and Research. Treatment of Major Depression: Vol 2. Treatment of Major Depression, Clinical Practice Guideline No 5. Rockville, Md: Agency for Health Care Policy and Research; 1993. AHCPR Publication No. 93-0551.
8. Sartorius N. The economic and societal burden of depression. J Clin Psychiatry. 2001;62:S8-S11.
9. Department of Health and Human Services, National Institute for Mental Health, Office of the Assistant Secretary for Planning and Evaluation. Access and utilization of new antidepressants and antipsychotic medications. 2000. Available at: http://www.aspe.hhs.gov/health/reports/
psychmedaccess. Accessed April 8, 2005.
10. Theobald DE, Kasper M, Nick-Kresl CA, Rader M, Passik SD. Documentation of indicators for antidepressant treatment and response in an HMO primary care population. J Managed Care Pharm. 2000;6:494-498.
11. Goodnick PJ, Henry JH, Buki VM. Treatment of depression in patients with diabetes mellitus. J Clin Psychiatry. 1995;56:128-136.
12. Feldman E, Mayou R, Hawton K, et al. Psychiatric disorder in medical in-patients. QJ Med. 1987;63:405-412.
13. US Public Health Service. Depression in adults. Am Fam Physician. 1995;51:1701-1704.
14. Ohayon MM, Morselli PL, Guilleminault C. Prevalence of nightmares and their relationship to psychopathology and daytime functioning in insomnia subjects. Sleep. 1997;20:340-348.
15. Morselli PL, Elgie R. GAMIAN-Europe/BEAM survey I—global analysis of a patient questionnaire circulated to 3,450 members of 12 European advocacy groups operating in the field of mood disorders. Bipolar Disord. 2003;5:265-278.
16. Agency for Health Care Policy and Research. Depression in Primary Care: Detection and Diagnosis. Vol 1. Detection and Diagnosis, Clinical Guideline Number 5. Rockville, Md: Agency for Health Care Policy and Research; 1993. AHCPR Publication No. 93-0550.
17. Dubovsky SL, Buzan R. Mood disorders. In: Hales RE, Yudofsky SC, Talbott JA, eds. The American Psychiatric Press Textbook of Psychiatry. 3rd ed. Washington, DC: American Psychiatric Press; 1999:479-565.
18. Ohayon MM. The effects of breathing-related sleep disorders on mood disturbances in the general population. J Clin Psychiatry. 2003;64:1195-1200.
19. Zammit GK, Weiner J, Damato N, Sillup GP, McMillan CA. Quality of life in people with insomnia. Sleep. 1999;22:S379-S385.
20. Morawetz D. Insomnia and depression: which comes first? Sleep Research Online. 2003;5:77-81. Available at: http://www.sro.org/2003/Morawetz/
77/. Accessed April 8, 2005.
21. He J, Kryger MH, Zorick FJ, et al. Mortality and apnea index in obstructive sleep apnea: experience in 385 male patients. Chest. 1988;94:9-14.
22. Reeves-Hoche MK, Meck R, Zwillich CW, et al. Nasal CPAP: an objective evaluation of patient compliance. Am J Respir Crit Care Dis. 1994;149:149-154.
23. Waldhorn RE, Herrick TW, Nguyen MC, et al. Long-term compliance with nasal CPAP therapy of obstructive sleep apnea. Chest. 1990;97:33-38.
24. Masdon JL, Magnuson JS, Youngblood G. The effects of upper airway surgery for obstructive sleep apnea on nasal continuous positive airway pressure settings. Laryngoscope. 2004;114:205-207.
John D. Zoidis is a contributing writer for Sleep Review.