Understanding the Burden of Depression

Larry Culpepper, MD, MPH

Department of Family Medicine, Boston University School of Medicine and Boston Medical Center, Boston, Massachusetts

The 12-month prevalence of MDD in US adults is approximately 7%, and the lifetime prevalence is approximately 16%.1 The yearly financial burden is more than $80 billion in the United States, including direct health care costs, suicide mortality costs, and lost workplace productivity costs.2 Initial depressive onset typically happens in early adulthood but can occur during later stages of life3; about 3% of the elderly in the general community setting, 17% to 37% of primary care patients who are 65 years or older, and 12% to 30% of those in long-term care facilities experience major depression.4

Historically, depression has increased with economic hardship.5 Factors such as job loss6 can contribute to the already high risk of recurrent depression, which may last well beyond the resolution of financial troubles. Therefore, in light of the recent economic decline, physicians in the primary care and psychiatric settings should be aware of the burden of depression and the potential consequences of suboptimal treatment for MDD. See AV 1AV 1 for an example of a discussion between a physician and a patient about the role of the depressive burden in antidepressant therapy.


Burden of MDD

Among patients with MDD, almost 90% have moderate to very severe depression.1 Kessler et al1 reported that almost half of patients who experienced a depressive episode received no health care treatment during a 1-year follow-up, and of those who did, nearly 60% received inadequate treatment. Unfortunately, even among patients being treated adequately, response (ie, symptom reduction ≥ 50%)7 without remission is common; the STAR*D study8 found that initial treatment led to remission in only one-third of patients. Further, relapse occurred in 34% of patients who reached remission after 1 treatment step and 50% of patients who required 4 treatment steps to reach remission.


The impact of MDD on quality of life can be as great as or greater than that of chronic medical diseases such as diabetes.9,10 Depending on depression severity, an average of 59% of patients with MDD report severe or very severe role impairment in at least 1 of the following domains: work, home, relationship, and social roles (AV 2AV 2).1

Suicidality is also associated with MDD. Patients with affective disorders have a 2.2% lifetime risk of suicide compared with less than 0.05% for those without affective disorders.11

Impact of MDD on Medical Illness

The presence of MDD is associated with an increased incidence of a number of medical conditions, including diabetes,12 hypertension,13 and stroke.14 In patients who have existing medical conditions, the presence of MDD is associated with increased morbidity/mortality. For example, patients with stable coronary artery disease15 or with unstable angina16 are more likely to experience fatal or nonfatal cardiac events (eg, myocardial infarction) if they have comorbid depression. Survival after myocardial infarction appears to be reduced among patients with depression, especially those with first-episode depression.17 Among patients with congestive heart failure, the risk of death after 30-month follow-up is 8 times greater in depressed patients than in those without depression.18

The presence of depression appears to increase the risk of rehospitalization among patients with general medical conditions. A study19 of inpatients with a history of at least 1 prior admission within the previous 6 months found that those who screened positive for depression were 3 times more likely to be rehospitalized within 90 days.

Impact of MDD on Neuropathology

Depression may have a significant impact on brain physiology. A 3-year study20 found a decrease in gray matter density in depressed patients relative to control subjects in areas of the brain associated with higher cognitive functioning, executive functioning, and emotional functioning, including the hippocampus, the anterior cingulum, the right dorsomedial prefrontal cortex, and the left amygdala. Patients who achieved remission during the prospective study had less decrease in gray matter density than patients who were not able to achieve remission. Hippocampal volume, which is involved in memory processing and the use of memory in terms of our response to the world, decreases as the number of episodes of depressive illness increases.21


A number of individuals experience major depression as a component of Alzheimer’s disease, but MDD also increases the risk of dementia. A 30-year study22 found that individuals with 3 or more depression episodes that led to hospital admission had a greater incidence of subsequent dementia compared with those who had had 1 or 2 hospitalizations for depression (AV 2AV 3). A postmortem study23 of patients with Alzheimer’s disease showed that MDD was associated with a significant increase in both neuritic plaques (P<.005) and neurofibrillary tangles (P<.002)—the hallmark pathologies of Alzheimer’s disease—compared with patients without MDD. Among the patients with Alzheimer’s disease, those with a history of depression had had faster cognitive decline than those without depression (P<.004).

Burden of Treatment-Resistant MDD

A subset of patients with MDD has treatment-resistant depression,24 defined as depression that has not responded to at least 2 different antidepressants administered at an adequate dose for an adequate duration.25 Treatment-resistant depression leads to increased health care utilization and incurs higher costs than nonresistant depression. A study26 found that patients with treatment-resistant depression were hospitalized at least twice as often and, on average, had total medical costs that were 6 times greater than patients whose depression was not resistant. Additionally, among outpatients with treatment-resistant depression, more than half of patients reported suicidal ideation and prominent hopelessness.27

Treatment-resistant depression is associated not only with decreased quality of life but also with increased mortality.28 In patients with coronary heart disease, especially those who have had acute coronary syndrome, cardiac morbidity and mortality are greater among those with treatment-resistant depression.29 One 7-year follow-up study30 found a doubling of cardiac mortality among patients whose depression failed to improve during the 6 months following acute coronary syndrome. Treatment-resistant depression is also associated with about a 2-fold increase in mortality in patients with stable COPD31 and, in patients with diabetes, about a 2-fold increase in the likelihood of poor adherence to medications for diabetes, dyslipidemia, and hypertension.32


The burden of MDD on individuals includes impaired role functioning, decreased quality of life, the development of medical conditions, increased morbidity and mortality, and increased health care services utilization and cost. The burden is increased across all areas for individuals not achieving remission and especially for those with treatment-resistant depression. Low rates of remission and high rates of relapse and recurrence demonstrate the inadequacy of available treatment options. However, as many patients receive no treatment or suboptimal treatment for MDD, outcomes for many patients may still be improved while more effective treatments are being developed. For information about implementing up-to-date practice recommendations for MDD screening and treatment so as to minimize the burden of MDD on individuals and the health care system, see the rest of this series on “Depression: When Initial Therapy Fails.”

For Clinical Use


  • To reduce the burden of depression, provide adequate treatment to improve the chances of full remission
  • Screen patients with MDD, especially those with treatment resistance, for medical sequelae


Drug Names

No drugs were mentioned in this activity


COPD = chronic obstructive pulmonary disease, MDD = major depressive disorder, QIDS-SR = Quick Inventory of Depressive Symptomatology Self-Report, SDS = Sheehan Disability Scale, STAR*D = Sequenced Treatment Alternatives to Relieve Depression

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