Anxiety and Depression in Chronic Obstructive Pulmonary Disease: Recognition and Management

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Anxiety and depression are common in patients with chronic obstructive pulmonary disease (COPD), occurring more frequently than in the general population1-4 or patients with other chronic diseases such as hypertension, diabetes, cancer, or musculoskeletal disorders.5,6 Their presence is associated with worse outcomes of COPD, and increased morbidity, mortality, disability, and health care expenditure.6-8 In spite of this, both anxiety and depression are frequently overlooked and undertreated in patients with COPD,9 and symptoms of anxiety and depression can overlap significantly, as well as overlap with COPD symptoms.7,10

Comorbid depressive disorders that may occur in patients with COPD include major depressive disorder, dysthymias (chronic depressive symptoms of mild severity), and minor depression.11 Depressive disorders are characterized by feelings of sadness, emptiness, and/or irritability, along with cognitive and somatic symptoms, which have a detrimental effect on the patient’s ability to function.11 Anxiety disorders include generalized anxiety disorder (GAD), phobias, and panic disorders.11 The main features of anxiety disorders, such as excessive fear and anxiety, may be accompanied by behavioral disturbances related to these symptoms, such as panic attacks and avoidance.11,12

The reported prevalence of depression in COPD varies widely between studies, owing to differences in sampling methods and degrees of illness severity used in assessment of depression6; rates have been reported to range from 10% to 42% in patients with stable COPD,6,13 and from 10% to 86% in patients with acute COPD exacerbation.14 Individuals with severe COPD are twice as likely to develop depression than patients with mild COPD.10

Prevalence rates for clinical anxiety in COPD range from 13% to 46% in outpatients and 10% to 55% among inpatients. GAD, panic disorders, and specific phobias are reported most frequently.15 Patients with COPD are 85% more likely to develop anxiety disorders compared with matched controls without COPD,4 and panic disorder is reported with a prevalence that is up to 10-fold higher than in the general population.16

Global prevalence rates of anxiety and depression are 1.8- and 1.4-fold higher in women than men, respectively17; the same gender difference is observed in patients with COPD.6 The higher prevalence rates of anxiety and depression in women are thought to be a result of sex differences in brain structure, function, and stress responses, as well as differences in exposure to reproductive hormones, social constraints, and experiences between women and men.18 However, psychologic comorbidity is an issue for both men and women with COPD, so it is important that clinicians are vigilant in recognizing anxiety and depression in both sexes, and are careful not to underestimate the burden in the male patient population.

It is also important to note that depression and anxiety often occur simultaneously in patients with COPD, with prevalence estimates of 26% to 43%.9,19,20 COPD patients with both depression and anxiety are at a heightened risk of suicidal ideation, increased physical disability, and chronic depressive symptoms versus those with either disorder alone.10,15 It is therefore important that comorbid anxiety and depression is not overlooked in patients with COPD.

Ensuring that anxiety and depression are recognized and treated effectively in patients with COPD is essential for optimizing outcomes. Primary care practitioners are well placed to diagnose anxiety and depression, and to ensure these conditions are suitably managed alongside treatments of COPD.

Potential mechanisms of anxiety and depression in COPD

Growing evidence suggests that the relationship between mood disorders—particularly depression—and COPD is bidirectional, meaning that mood disorders adversely impact prognosis in COPD, whereas COPD increases the risk of developing depression.21 For example, in a study of
60 stable patients with COPD, elevated dyspnea and reduced exercise capacity were the predominant mechanisms leading to anxiety and depression symptoms associated with the condition.22 In addition, the risk of new-onset depression was increased in COPD patients with moderate-to-severe dyspnea in a 3-year follow-up study.23 Conversely, depression has been shown to be a significant risk factor for disabling dyspnea (modified Medical Research Council score ≥2) in patients with COPD.24

COPD can lead to feelings of hopelessness, social isolation, reduced physical functioning, and sedentary lifestyle, all of which are associated with an increased level of depressive symptoms.25 Similarly, inadequate social support increases the risk of anxiety in patients with COPD.26 Therefore, ensuring that patients with COPD have high-quality support is very important for reducing anxiety and depressive symptoms.27

The exact mechanisms for the association between mood disorders and COPD remain unclear.7,10 Research to date indicates that the relationship between depression and impaired pulmonary function may be partly mediated by chronic inflammation7,10; systemic inflammation has been associated with other comorbidities of COPD (eg, muscle wasting and osteoporosis),28 and emerging data appear to show that proinflammatory cytokines partly mediate the association between depressive symptoms and pulmonary function.29 Smoking and hypoxemia may also influence the prevalence of depression in COPD, but symptom severity and impaired quality of life remain the most important determinants.6,30

Clinical studies have demonstrated that a number of patient-related factors, including female gender, younger age, current smoking, greater severity of airflow limitation, and lower socioeconomic status, are associated with a higher prevalence and/or increased risk of depression and/or anxiety in COPD.3,4,30,31 Frequent episodes of rehospitalization, and comorbidities such as hypertension, arthritis, cancer, and heart disease, have been found to increase the risk of anxiety and depression in patients with COPD.3,32 Risk of anxiety has been shown to increase with greater dyspnea severity.4 Pain, a frequently overlooked symptom in COPD, has been shown to be associated with symptoms of both anxiety and depression in patients with COPD.33 This is driven by worsened quality of life and sleep quality, decreased physical activity, and an increased fear of movement that occur as a result of pain.34

The impact of anxiety and depression in COPD

Comorbid anxiety and depression have a significant detrimental impact on morbidity and mortality in patients with COPD. Both disorders have been associated with an increased risk of death in COPD.13,35-37 Indeed, of 12 comorbidities proposed to be predictors of mortality in a cohort of 187 female outpatients with COPD, anxiety was associated with the highest risk of death.35,36

In addition, patients with COPD and anxiety and/or depression have a higher risk of COPD exacerbations,4,8,23,36,38-40 hospitalization,41,42 rehospitalization,14,36,43 longer hospital stays,37,41,44 and mortality after exacerbations,14,36,41 compared with patients without these comorbidities. Patients with COPD who have elevated anxiety symptoms also often experience their first hospitalization earlier in the natural course of COPD than those without anxiety.36

Psychologic comorbidities are also associated with worse lung function, dyspnea, and respiratory symptom burden in patients with COPD.37,40 Patients with COPD and anxiety are more likely to experience greater dyspnea at an earlier stage of disease than those without anxiety.36 Persistent smoking at 6 months after hospitalization for an acute exacerbation of COPD is also more likely to be seen in patients with depression.37

Patient-centered outcomes are worse in COPD patients with mood disorders. Both anxiety and depression have been shown to correlate with significantly reduced health-related quality of life (HRQoL), poorer physical health status, functional limitations, and reduced exercise capacity.4,23,37,40,45 The presence of either anxiety or depression at baseline has been shown to correlate with reduced HRQoL at 1-year follow-up, but depression appears to be the stronger predictor of low future HRQoL than anxiety.45

Additionally, mood disorders—particularly depression—reduce physical activity in patients with COPD.46,47 Emotional responses to COPD symptoms, such as dyspnea, can further decrease activity and worsen deconditioning, resulting in a downward spiral of reduced inactivity, social isolation, fear, anxiety, and depression.48

COPD patients with any comorbidity exhibit lower rates of medication adherence than those without comorbidities.49-51 Clinical studies have demonstrated that anxiety and depression are significant predictors of poor adherence to COPD interventions, including pulmonary rehabilitation (PR).51-55 Nonadherence to COPD therapies is associated with poor clinical outcomes, including higher hospitalization rates and increased emergency department visits, and increased costs.56,57 Health care expenditure, in terms of both specific COPD-related costs and general “all-cause” costs, is significantly higher in COPD patients with anxiety and/or depression than in those without.8

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