Overview

Depression is a comorbid disabling syndrome that affects approximately 15% to 25% of cancer patients.[1-4] Depression is believed to affect men and women with cancer equally, and gender-related differences in prevalence and severity have not been adequately evaluated.[5] Individuals and families who face a diagnosis of cancer will experience varying levels of stress and emotional upset. Depression in patients with cancer not only affects the patients themselves but also has a major negative impact on their families. A survey in England of women with breast cancer showed that among several factors, depression was the strongest predictor of emotional and behavioral problems in their children.[6] Fear of death, disruption of life plans, changes in body image and self-esteem, changes in social role and lifestyle, and financial and legal concerns are significant issues in the life of any person with cancer, yet serious depression or anxiety is not experienced by everyone who is diagnosed with cancer.

Just as patients require ongoing evaluation for depression and anxiety throughout their course of treatment, so do family caregivers. In a study of family caregivers of patients in the palliative phase of illness, both male and female caregivers experienced significantly more anxiety than normal samples, while there was an increased incidence of Hospital Anxiety and Depression Scale–defined depression among women.[7]

There are many myths about cancer and how people cope with it, such as the following:

• All people with cancer are depressed.
• Depression in a person with cancer is normal.
• Treatments are not helpful.
• Everyone with cancer faces suffering and a painful death.

Sadness and grief are normal reactions to the crises faced during cancer. All people will experience these reactions periodically. Because sadness is common, it is important to distinguish between normal degrees of sadness and depressive disorders. An end-of-life consensus panel review article describes details regarding this important distinction and illustrates the major points using case vignettes.[8] A critical part of cancer care is the recognition of the levels of depression present and determination of the appropriate level of intervention, ranging from brief counseling or support groups to medication and/or psychotherapy. For example, relaxation and counseling interventions have been shown to reduce psychological symptoms in women with a new diagnosis of gynecological cancer.[9] Some people may have more difficulty adjusting to the diagnosis of cancer than others and will vary in their responses to the diagnosis. Major depression is not simply sadness or a blue mood. Major depression affects approximately 25% of patients and has recognizable symptoms that can and should be diagnosed and treated because they have an impact on quality of life.[10,11] Depression is also an underdiagnosed disorder in the general population. Symptoms evident at the time of a cancer diagnosis may represent a preexisting condition and warrant separate evaluation and treatment.

Depression and anxiety disorders are common among patients receiving palliative care and contribute to a greatly diminished quality of life in these patients.[12] In the Canadian National Palliative Care Survey, patients receiving palliative care for cancer (n = 381) were evaluated for depressive and anxiety disorders and for the impact of these disorders on quality of life. The primary assessment tool was a modified version of the Primary Care Evaluation of Mental Disorders (PRIME-MD). A significant number of participants (24.4%; 95% confidence interval, 20.2–29.0) were found to fulfill diagnostic criteria for at least one depressive or anxiety disorder (20.7% prevalence for depressive disorder and 13.1% for anxiety disorder). Participants diagnosed with a disorder were significantly younger than the other participants (P = .002), had lower performance status (P = .017), had smaller social networks (P = .008), and participated less in organized religious services (P = .007). They also reported more severe distress about physical symptoms, social concerns, and existential issues, suggesting significant negative impact on other aspects of their quality of life.[12] The importance of psychological issues was underscored by another study conducted in terminally ill cancer patients (n = 211) with life expectancies of less than 6 months. Using specific validated psychometrics (e.g., visual analog scale), investigators evaluated patient “sense of burden to others” and its correlation with physical, psychological, and existential issues. The variables most highly correlated with sense of burden to others included depression (r = 0.460, P < .0001), hopelessness (r = 0.420, P < .0001), and outlook (r = 0.362, P < .0001). In multiple regression analysis, four variables emerged predicting perception of burden to others: depression, hopelessness, level of fatigue, and current quality of life. No association between sense of burden to others and actual degree of physical dependency was found, implying that this perception is mainly mediated through psychological distress and existential issues. A subanalysis of patient groups from different settings suggested that these findings were consistent across the inpatient and outpatient settings, with some minor variations.[13]

Normally, a patient's initial emotional response to a diagnosis of cancer is brief, extending over several days to weeks, and may include feelings of disbelief, denial, or despair. This normal response is part of a spectrum of depressive symptoms that range from normal sadness to adjustment disorder with depressed mood to major depression.[8] Other syndromes described include dysthymia and subsyndromal depression (also called minor depression or subclinical depression). Dysthymia is a chronic mood disorder in which a depressed mood is present on more days than not for at least 2 years. In contrast, subsyndromal depression is an acute mood disorder that is less severe (some, but not all, diagnostic symptoms present) than major depression.

The emotional response to a diagnosis of cancer (or cancer relapse) may begin as a dysphoric period marked by increasing turmoil. The individual will experience sleep and appetite disturbance, anxiety, ruminative thoughts, and fears about the future. Epidemiologic studies, however, suggest that at least one half of all people diagnosed with cancer will successfully adapt. Markers of successful adaptation include maintaining active involvement in daily life; minimizing the disruptions caused by the illness to one's life roles (e.g., spouse, parent, employee); regulating the normal emotional reactions to the illness; and managing feelings of hopelessness, helplessness, worthlessness, and/or guilt.[14] Some studies suggest an association between maladaptive coping styles with higher levels of depression, anxiety, and fatigue symptoms.[15,16] Examples of maladaptive coping behaviors include avoidant or negative coping, negative self-coping statements, preoccupation with physical symptoms, and catastrophizing. One study conducted in a group of 86 mostly late-stage cancer patients suggested that maladaptive coping styles and higher levels of depressive symptoms are potential predictors of the timing of disease progression.[16] Another study examining coping strategies in women with breast cancer (n = 138) concluded that patients with better coping skills such as positive self-statements have lower levels of depressive and anxiety symptoms.[15] The same study found racial differences in the use of coping strategies, with African American women reporting and benefiting more from the use of religious coping strategies such as prayer and hopefulness than did Caucasian women.[15] Preliminary data suggest a beneficial impact of spirituality on associated depression, as measured by the Functional Assessment of Chronic Illness Therapy—Spiritual Well-Being (FACIT-Sp) and the Hamilton Depression Rating Scale.[17]

The following indicators may suggest a need for early intervention:

• A history of depression.
• A weak social support system (not married, few friends, a solitary work environment).
• Evidence of persistent irrational beliefs or negativistic thinking regarding the diagnosis.
• A more serious prognosis.
• Greater dysfunction related to cancer.

As shown by a study of adult cancer patients (n = 48) and their adult relatives (n = 99), family functioning is an important factor that impacts patient and family distress. Families that were able to act openly, express feelings directly, and solve problems effectively had lower levels of depression, and direct communication of information within the family was associated with lower levels of anxiety.[18] Depressive symptoms in spouses of patients with cancer can also have a negative impact on their marital communication. A preliminary study investigated 19 potential predictors of depression in spouses (n = 206) of women with nonmetastatic breast cancer.[19] Spouses were more likely to experience depressive symptoms if they were older, were less well educated, were more recently married, reported heightened fears over their wife's well-being, worried about their job performance, were more uncertain about their future, or were in less well-adjusted marriages.[19]

Risk factors may be different, especially pain and other physical symptoms.[20] When the clinician begins to suspect that a patient is depressed, he or she will assess the patient for symptoms. Mild or subclinical levels of depression that include some, but not all, of the diagnostic criteria for a major depressive episode can cause considerable distress and may warrant interventions such as supportive individual or group counseling, either by a mental health professional or through participation in a self-help support group.[21] Evidence-based recommendations have been published describing various approaches to the problems of cancer-related fatigue, anorexia, depression, and dyspnea.[22] Even in the absence of any symptoms, many patients express interest in supportive counseling, and clinicians should try to accommodate those patients by a referral to a qualified mental health professional. When symptoms are more intense, longer lasting, or recurrent after apparent resolution, however, treatment to alleviate symptoms is essential.[11,23,24] Anxiety and depression in early treatment are good predictors of these same problems at 6 months.[25] In a study of older women with breast cancer, a recent diagnosis of depression was associated with both a greater likelihood of not receiving definitive cancer treatment and poorer survival.[26]

The pathophysiology of cancer-related depression remains unclear and probably encompasses many mechanisms. A study of patients with advanced metastatic cancer showed that both plasma interleukin-6 (IL-6) concentrations and hypothalamic-pituitary-adrenal (HPA) axis dysfunction were markedly higher in patients with clinical depression.[27] A cut-off value of 10.6 pg/mL for IL-6 yielded a sensitivity of 79% and specificity of 87%, while a cut-off value of 33.5% for cortisol variations yielded a sensitivity of 81% and specificity of 88%. One limitation of this study was that neither pain levels nor fatigue levels were measured, which might independently affect these relationships.

In this summary, unless otherwise stated, evidence and practice issues as they relate to adults are discussed. The evidence and application to practice related to children may differ significantly from information related to adults. When specific information about the care of children is available, it is summarized under its own heading.

References

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