Focus on Depression

Depression: Overview, Risk Factors and Comorbidities

The leading cause of disability in the world is not, as many believe, cardiovascular disease or arthritis, but depression.^[1] Depressive disorders, a classification that encompasses several related but distinct diagnoses, affect an estimated 19 million American adults, or nearly 10% of the population over age 18.^[2]

Three of five patients with depression also face the challenge of one or more other behavioral comorbidities.^[3] Depressive disorders are most frequently associated with anxiety disorders, leading some researchers to believe that the two types of disorders share the same causes or reflect a similar genetic background.^[4][5]

Depressive and anxiety disorders, like other behavioral disorders, are classified in the United States according to the American Psychiatric Association’s Diagnostic and Statistical Manual (DSM-IV-TR™). The individual disorders that are classified as depression and anxiety are briefly described on the following pages, and the number of affected patients in the United States is shown in Table 1. These disorders are substantial contributors to both health care costs and disability; three (major depressive disorder, bipolar disorder, and obsessive-compulsive disorder [OCD]) are among the 10 leading causes of disability in the United States.^[2]

• Major depressive disorder involves persistent periods of depressed mood, and/or loss of interest or pleasure in nearly all activities, that last at least two weeks with symptoms present nearly all day, every day. Patients with major depressive disorder may also suffer from lethargy, disrupted sleep and appetite, difficulty concentrating, and feelings of worthlessness or guilt. The lifetime risk of suicide among patients who have been diagnosed with major depressive disorder may be as high as 15% and the rate of death, in general, is much higher than in the general population.^[6]
  


• Dysthymic disorder involves less severe symptoms of depression, which are present more days than not, that persist for a prolonged period (at least two years). Patients with dysthymic disorder frequently develop major depressive disorder as well.^[6]
  


• Bipolar disorder (mood disorder with depressive features) is characterized by episodes of mania - an abnormally elevated or irritable mood, usually accompanied by an inflated self-esteem, decreased sleep, excessive talkativeness, restlessness, distractibility, and/or inappropriate involvement in activities. Patients with bipolar disorder typically also experience episodes of depression and, as with major depression, are at high risk for suicide.^[6]
  

• Generalized anxiety disorder (GAD) is characterized by anxiety or worry about real or imagined events or activities that are far out of proportion to their actual impact. This anxiety impairs the ability of the patient to function, and the focus of the anxiety may shift over time.^[6]
  


• Panic disorder involves recurrent panic attacks - periods of intense fear in the absence of real danger. Between these attacks, the patient is concerned about the possibility or consequences of another attack.^[6]
  


• Obsessive-compulsive disorder (OCD) involves recurrent obsessions (inappropriate ideas or thoughts that cause anxiety or distress) or compulsions (repetitive behaviors that do not provide pleasure or gratification). These are severe enough to cause distress or are excessively time-consuming and the patient, at some point, recognizes their inappropriateness.^[6]
  


• Posttraumatic stress disorder (PTSD) is characterized by intense fear, helplessness, or horror for more than one month following an extremely traumatic event. Patients often feel as if they are reexperiencing the event, and their symptoms intrude on their ability to function normally.^[6]
  


• Social phobia is a persistent fear of embarrassment in social or performance situations that significantly impairs the patient’s ability to function. Patients often recognize the unreasonableness of the fear and usually try to avoid the feared situation; they suffer profound anxiety prior to an anticipated event.^[6]
  


• Agoraphobia is anxiety about being in places or situations from which the patient cannot escape or in which they may suffer a panic attack or panic symptoms. Patients usually respond to agoraphobia by avoiding social and other anxiety-producing situations; they may be unable to leave their homes. Agoraphobia and panic disorder frequently co-occur.^[6]
  

Research has shown that the chance that a person will develop depression is heightened by the presence of a number of risk factors. For example, most depressive and anxiety disorders are about twice as common among women as men; the prevalence of major depressive disorder is 6.5% among women and 3.3% among men. The exceptions to this pattern are bipolar disorder, OCD, and social phobia, which affect roughly equal numbers of women and men.[2]

A family history of depression (in a first-degree relative) increases the risk of major depressive disorder by about one and a half to three times the risk in people without such a history. This suggests that the tendency to develop depression may be, in part, inherited^[6]

The presence of another behavioral disorder, especially an anxiety disorder, strongly increases the risk of developing a depressive disorder. In fact, survey-based research suggests that most cases of major depressive disorder are secondary, occurring in people with a history of another behavioral disorder.^[7]

Although depressive disorders tend to begin in early adulthood, the elderly are also at increased risk. About two million of the 35 million Americans over age 65 have a depressive disorder, and an additional five million are estimated to have depressive symptoms that don’t reach the severity of a major disorder. In part, the risk of depression among the elderly is a consequence of the increased prevalence of chronic medical problems. Depressive disorders contribute to a disproportionate risk of suicide among the elderly, who account for 18% of suicides despite making up only 13% of the population.^[8]

Psychological stress contributes strongly to depressive disorders. Depressive episodes frequently follow severely stressful events, including divorce, serious illness (see next section), or death of a loved one. These events seem to contribute more strongly to an initial depressive episode than to recurrent ones.^[6]

The effect of emotional trauma in precipitating depressive and anxiety disorders is not limited to personal and private events. For example, the terrorist attacks of September 11, 2001, led to a dramatic increase in the prevalence of PTSD, especially for those living in close proximity to the World Trade Center. Among those near the site, the prevalence was 20%, compared with 8% in Manhattan generally.^[9]

Depressive disorders are strongly linked to physical illness. The prevalence of clinical symptoms of depressive disorders is estimated to be three- to nine-fold greater in patients with nonpsychiatric medical conditions than in the general population.10 Depression has been shown to increase the risk of disability and mortality and to slow the rate of recovery associated with specific conditions.^[10] Depression is a prominent feature of chronic illnesses, neurodegenerative diseases, serious infectious diseases, and cancer, among other conditions. Following, the relationship between depression and some selected illnesses is described.

• Coronary heart disease: The rate of depressive symptoms following a myocardial infarction (MI) ranges from 40% to 65%, and 18% to 25% of patients develop major depressive disorder following an MI. In patients with coronary heart disease and major depressive disorder, depression is associated with an added degree of disability equivalent to the heart disease itself. Post-MI patients with depressive symptoms have a much higher risk of death than nondepressed patients. In addition, they are slower to return to work and experience more social problems and stress.^[11]
  


• Diabetes: Major depressive disorder is about three-fold more common among patients with diabetes than among the population at large. Depression in diabetic patients can lead to poor disease management (poorly controlled blood glucose), which in turn leads to an increased risk of complications.^[10]
  
• Chronic pain: Many patients with chronic pain syndromes develop depressive symptoms. The lifetime prevalence of major depressive disorder among patients with fibromyalgia has been estimated at 71%.^[10],[11]
  


• Dementia: The diagnosis of depression in patients with dementia can be extremely difficult, as many of the symptoms of depression (apathy, memory loss, poor concentration) are the same as those of early dementia. The relationship of depressive disorders and dementia may be two-way; both major depressive disorder and bipolar disorder have been linked to an increased risk for later development of dementia. About 30% to 40% of patients with Alzheimer’s disease are estimated to have depressive symptoms.^[10],[12]
  
• Cancer: Because cancer is such a devastating disease, most patients experience substantial behavioral and mood symptoms immediately following diagnosis. Although many patients rebound from this period of turmoil, some go on to develop depressive disorders. Estimates of prevalence vary, but one large study suggested that the prevalence of depressive disorders among cancer patients is 13%. The risk of major depressive disorder rises in patients with advanced cancer and/or those with substantial pain or disability. In addition, some drugs used in cancer treatment are associated with effects on mood. Depression in cancer patients leads to poor functioning and reduces the ability to follow medical recommendations.^[10]
  
• HIV/AIDS: Depression affects an estimated 20% to 32% of HIV-positive patients. Untreated depression in HIV-positive individuals is associated with increased resource utilization and higher rates of risky behaviors. In addition, depression has been linked to more rapid disease progression and shortened life span.^[13],[14]
  


• Trauma: Severe physical injury can lead to a number of behavioral disorders. A recent study of patients following a lower-limb injury found that 48% demonstrated evidence of a depressive or anxiety disorder. These symptoms are notable for their persistence. Two years after the injury, the rate was 45%, and symptoms (especially for depression and phobic anxiety) remained severe in one of five patients.^[15]
  

HOW ARE WE DOING? RECOGNITION AND TREATMENT OF BEHAVIORAL DISORDERS

As with many other health conditions, the personal, social, and economic toll exacted by behavioral disorders could be substantially reduced by closing existing gaps in quality related to both diagnosis and treatment. Of even more concern is that, in contrast to the gradual but steady progress noted in the treatment of other chronic illnesses, the quality of management of depression and related disorders seems to be stagnant, and in some instances, even declining.^[16]

These trends are documented in NCQA’s The State of Health Care Quality, 2003, which tracks specific indicators of treatment effectiveness for many conditions, including depression. Figure 1 illustrates one such indicator. Antidepressant Medication Management: Optimal Practitioner Contact for Medication Management (Optimal Practitioner Contact) assesses the percentage of patients who received the recommended three or more follow-up office visits with a primary care physician (PCP) or mental health provider in the 12-week, acute-treatment phase after a diagnosis of depression and subsequent prescription of antidepressant medication.^[16],[17]

• The proportion of patients receiving appropriate care actually declined during the period of 1998 to 2002 from 22.8% to 19.2%.^[16],[17]
  


• The variance in quality between health plans is as alarming as the overall decline. Although the worst performing plans improved somewhat, there was still a three-fold difference between plans at the 10th and 90th percentiles in 2001.1^[16],[17]
  

Another HEDIS measure of the quality of depression management, Antidepressant Medication Management: Continuation Phase Treatment (Continuation Phase Treatment), addresses continuity of care. Figure 2 illustrates the percentage of patients who received effective treatment by remaining on antidepressant medication continuously in the six months after beginning medication for a new episode of depression.

• The 2002 results improved somewhat over the illustrated 2001 results--from 40.1% to 42.8%.^[16]
  


• The variance between health plans is similar to that observed for the Optimal Practitioner Contact measure, with a two and half-fold difference between plans at the 10th and 90th percentiles.^[16],[17]
  

This lack of progress stands in contrast to the uniform improvement in other HEDIS measures of Effectiveness of Care and to the expansion in the number of available depression treatment options, now comprising over two dozen prescription drugs with seven completely distinct mechanisms of action.^[18] This lack of progress is most likely attributable to the existence of multiple diagnosis and treatment barriers, which will be reviewed in detail in the next chapter. The effectiveness of antidepressant medications in both acute and continuation care has been demonstrated in multiple clinical studies. Many of these medications are effective in the treatment of a range of anxiety disorders as well, further suggesting an intimate relationship between depression and anxiety. For example, selective serotonin reuptake inhibitors (SSRIs) offer side effect profiles that have led to improvements in compliance and persistency in major depressive disorder, PTSD, and social phobia, among others.^[19]-[21] In addition to pharmacological approaches, several different types of psychosocial therapy (“talk therapy”) have demonstrated efficacy in depression management.^[22] For example, cognitive-behavioral therapy has been evaluated in over 80 controlled clinical studies, and has been shown to be at least as effective as pharmacological approaches in some patients.

Combinations of talk therapy and pharmacological therapy have also been evaluated in a number of studies. The combination approach has demonstrated superior effectiveness in several studies to treatment with either talk therapy or pharmacological therapy alone. Several studies have shown it to be especially useful in preventing relapse into depression among patients who had only a partial response to pharmacological therapy alone.^[23]

• In a 2000 survey of patients with bipolar disorder, the mean time between the onset of symptoms and seeking treatment was less than one year for only 36% of patients and was greater than 10 years for 31%. These numbers, although sobering, reflect some degree of improvement over the 1992 survey (30% and 36%, respectively).^[24]
  


• Only 5.4% of patients with social phobia seek treatment, although 33.5% report that the disorder has a considerable impact on their lives.^[25]
  


• Fewer than 40% of people reporting a serious mental illness in a recent survey received stable treatment during the preceding year.^[26]
  

AN URGENT NEED FOR IMPROVEMENT: THE COSTS OF INADEQUATE TREATMENT

Untreated or inadequately treated behavioral illnesses contribute to societal, economic, health, and personal costs:

• Lost productivity: The overall cost of depression in 2000 was estimated at $83.1 billion. Over three fifths of this cost ($51.5 billion, or 62%) was attributable to work-place costs, far exceeding the direct cost of treatment ($26.1 billion, or 31%).^[29] A 2003 study estimated the productivity cost of depression at $44 billion, emphasizing that most of this cost was due not to absenteeism, but to reduced on-the-job productivity (“presenteeism”).^[28],[29]
  


• Exacerbation of medical conditions: Some of the work impairments and lost productivity in individuals with hypertension, arthritis, asthma, and ulcers have been shown to be the result not of physical illness, but of comorbid behavioral disorders.^[30]
  


• Marital instability: A higher risk of divorce contributes to 23 million and 48 million lost years of marriage among men and women, respectively.^[31]
  


• Teenage pregnancy/parenthood: Behavioral disorders that occur during childhood and adolescence are associated with a two- to 12-fold increase in the risk of teen parenthood among both males and females.^[32]
  

Suicide is the most devastating consequence of untreated behavioral illness. Of the nearly 30,000 suicides annually in the United States, over 90% can be traced to a diagnosable behavioral disorder; nearly 60% involve major depressive disorder. In the year 2000, suicide was the third leading cause of death among adolescents and young adults ages 15 to 24 years.^[2][18]

With both high prevalence and devastating impact, depression outranks all other disease as a contributor to disability in the United States, incurring productivity losses that dwarf the resources devoted to its care. The immense toll exacted by depression is measured not only in economic terms, but also in shortened lives and damaged families. For the health care community, depression represents a largely unmet challenge-despite expanded and increasingly effective therapeutic alternatives, far too many patients remain undiagnosed or undertreated. Only by understanding the barriers standing in the way of effective management will it become possible to reduce personal and societal costs of depression.

[1] - Murray CJL, Lopez AD, eds.
Summary: The global burden of disease: a comprehensive assessment of mortality and disability from diseases, injuries, and risk factors in 1990 and projected to 2020. Cambridge, MA: Published by the Harvard School of Public Health on behalf of the World Health Organization and the World Bank, Harvard University Press, 1996. Internet summary available at http://www.who.int/msa/mnh/ems/dalys/intro.htm Accessed March 19, 2004.

[2] - National Institute of Mental Health, National Institutes of Health. The numbers count; mental disorders in America. Available at: http://www.nimh.nih.gov/publicat/numbers.cfm#3 Accessed January 7, 2004.

[3] - Wittchen HU, Lieb R, Wunderlich U, Schuster P. Comorbidity in primary care: presentation and consequences. J Clin Psychiatry. 1999;60(suppl 7): 29-36, discussion 37-38.

[4] - Gorwood P. Generalized anxiety disorder and major depressive disorder comorbidity: an example of genetic pleiotropy? Eur Psychiatry. 2004;19:27-33.

[5] - Wittchen HU, Beesdo K, Bittner A, Goodwin RD. Depressive episodes-evidence for a casual role of primary anxiety disorders? Eur Psychiatry.2003;18:384-393.

[6] - American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Washington, DC: American Psychiatric Associations; 2000.

[7] - Kessler RC, Nelson Captain Bonneville, McGonagle KA, Liu J, Swartz M, Blazer DG. Comorbidity of DMS-III-R major depressive disorder in the general population: results from the US National Comorbidity Survey. Br J Psychiatry Suppl. 1996;(30):17-30.

[8] - . National Institute of Mental Health. National Institutes of Health. Older adults: depression and suicide facts. Available at http://www.nimh.nih.gov/publicat/elderlydepsuicide.cfm> Accessed March 8, 2004

[9] - Galea S, Ahem J, Resnick H, et al. Psychological sequelae of the September 11 terrorist attacks in New York City. N Engl J Med. 2002;346:982-987.

[10] - Agency for Health Care Policy and Research (AHCPR). Depression in Primary Care: Volume 1. Detection and diagnosis. 1993. Available at http://www.mentalhealth.com/bookah/p44-d1a.html#Head0 Accessed March 3, 2004.

[11] - Frasure-Smith N, Lesperance F, Talajic M. Depression and 18-month prognosis after myocardial infarction. Circulation. 1995;91:999-1005.

[12] - Kessing LV, Nilsson FM. Increased risk of developing dementia in patients with major affective disorders compared to patients with other medical illnesses. J Affect Disord. 2003;73:261-269.

[13] - Valente SM. Depression and HIV disease J Assoc Nurses AIDS Care. 2003;14:41-51.

[14] - Farinpour R, Miller EN, Satz P, et al. Psychosocial risk factors of HIV morbidity and mortality: findings from the Multicenter AIDS Cohort Study (MACS). J Clin Exp Neuropsychol. 2003;25:654-670.

[15] - McCarthy ML, MacKenzie EJ, Edwin D, Bosse MJ, Castillo RC, Starr A, for the LEAP study group. Psychological distress associated with severe lower-limb injury. J Bone Joint Surg Am. 2003;85-A:1689-1697.

[16] - National Committee for Quality Assurance. The State of Health Care Quality, 2003. Industry trends and analysis. Washington, DC: National Committee for Quality Assurance; 2003.

[17] - National Committee for Quality Assurance. The State of Health Care Quality, 2002. Antidepressant medication management. http://www.ncqa.org/sohc2002/SOHC_2002_AMM.html Accessed March 8, 2004.

[18] - Nierenberg AA. Current perspectives on the diagnosis and treatment of major depressive disorder. AM J Manag Care.2001;7(suppl 11):S353-S366.

[19] - Brady K, Pearlstein T, Asnis GM, et al. Efficacy and safety of sertraline treatment of posttraumatic stress disorder: a randomized controlled trial. JAMA. 2002;283:1837-1844.

[20] - Van Ameringen MA, Lane RM, Walker JR, et al. Sertraline treatment of generalized social phobia: a 20-week, double-blind, placebo-controlled study. Am J Psychiatry.2001;158:275-281.

[21] - Reimherr FW, Chouinard G, Cohn CK, et al. Antidepressant efficacy of sertraline: a double-blind, placebo- and amitriptyline-controlled, multicenter comparison study in outpatients with major depression. J Clin Psychiatry.1990;51(suppl B):18-27.

[22] - Agency for Health Care Policy and Research (AHCPR). Depression in Primary Care: Volume 2 - Treatment of Major Depression. 1993. Available at: http://www.mentalhealth.com/bookah/p44-d2.html Accessed March 3, 2004

[23] - American Psychiatric Association. Practice guideline for the treatment of patients with major depression. Available at: http://www.psych.org/psych-pract/treatg/pg/Depressoin2e.book.cfm Accessed January 7, 2004.

[24] - National Depressive and Manic-Depressive Association. Living with bipolar disorder: how far have we really come? Available at: http://www.dbsalliance.org/pdf/bphowfar1.pdf Accessed January 8, 2004.

[25] - Lepine JP. The epidemiology of anxiety disorders: prevalence and societal costs. J Clin Psychiatry.2002;63(suppl 14):4-8.

[26] - Kessler RC, Berglund PA, Bruce ML, et al. The prevalence and correlates of untreated serious mental illness. Health Serv Res.2001;36(6, pt1):987-1007.

[27] - Greenberg PE, Kessler RC, Birmbaum HG, et al. The economic burden of depression in the United States: how did it change between 1990 and 2000? J Clin Psychiatry.2003;64:1465-1475.

[28] - Avrichir BS, Elkis H. Prevalence and underrecognition of dysthymia among psychiatric outpatients in Sao Paulo, Brazil. J Affect Disord.2002;69:193-199.

[29] - Stewart WF, Ricci JA, Chee E, Hahn SR, Morganstein D. Cost of lost productive work time among US workers with depression. JAMA.2003;289:3135-3144.

[30] - Kessler RC, Ormel J, Demler O, Stang PE. Comorbid mental disorders account for the role impairment of commonly occurring chronic physical disorders: results from the National Comorbidity Survey. J Occup Environ Med. 2003;45:1257-1266.

[31] - Kessler RC, Walters EE, Forthofer MS. The social consequences of psychiatric disorders, III: probability of marital stability. AM J Psychiatry. 1998;155:1092-1096.

[32] - Kessler RC, Berglund PA, Foster CL, Saunders WB, Stang PE, Walters EE. Social consequences of psychiatric disorders, II: teenage parenthood. Am J Psychiatry.1997;154:1405-1411.