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National Cancer Institute
Last Modified: June 30, 2011
Depression is a comorbid disabling syndrome that affects approximately 15% to 25% of cancer patients. 1 2 3 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 Scaledefined depression among women. 7
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, 20.229.0) 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 TherapySpiritual Well-Being (FACIT-Sp) and the Hamilton Depression Rating Scale. 17
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.
Cognitive symptoms may express themselves as repeated and ruminative thoughts such as I brought this on myself," "God is punishing me," or "I'm letting my family down, and as fatalistic expectations concerning prognosis, despite realistic evidence to the contrary. Such thinking may predominate or may alternate with more realistic thinking, yet remain very stressful. Some individuals will share negativistic thoughts freely, and family members may be aware of them. Other patients will not volunteer such thinking but will respond to brief inquiries such as the following (other examples are listed in Table 1):
It is possible for a physician or nurse to ask these types of questions without becoming engaged in providing counseling themselves. Merely asking these questions will express concern and increase the likelihood that the patient will be receptive to suggestions for further counseling.
A statement such as the following can then follow these questions:
Many people with cancer sometimes have these feelings. You are not alone. But talking to someone else about them can greatly help. I'd like to suggest that you consider doing that. Would you be willing to talk to someone who has a lot of experience helping people cope with the stress of having cancer?
It is preferable at this time both to encourage the patient to seek out someone already known to him or her and to inform him or her of other resources in the community. Particularly for patients who have completed cancer treatment and who have manageable physical symptoms, higher perceived availability of social support has been associated with fewer depressive symptoms. 2 In some instances, referral to a clergy person or therapist may also be appropriate. Most therapists can address general issues of grief or fears about death; some will specialize in clinical health psychology, medical social work, or even working primarily with cancer patients. For the hesitant patient, suggesting multiple resources will increase the likelihood that some assistance will be sought. For other patients, a formal direct referral may be appropriate.
Evaluation of depression in people with cancer should include careful assessment of symptoms, treatment effects, laboratory data results, physical status, and mental status. Although the etiology of depression is largely unknown, many risk factors for depression are known (see list below). Limited data suggest that depressive symptomatology in cancer patients undergoing cytokine therapy with interferon-alfa and interleukin-2 may be mediated by changes in availability of neurotransmitter precursors. 3 For patients with head and neck cancer treated with curative intent, eight pretreatment variables (tumor stage, sex, depressive symptoms, openness to discuss cancer in the family, perceived available support, received emotional support, tumor-related symptoms, and size of the informal social network) can be used to predict which patients are likely to become depressed up to 3 years after treatment. 4 5 A prospective study of terminally ill Japanese patients who were assessed for psychiatric illness by structured clinical interview at the time of registration (baseline) and again at admission to a palliative care unit (follow-up) found that 5 (42%) of the 12 patients diagnosed with adjustment disorder at baseline progressed to major depression at follow-up. Only the Hospital Anxiety and Depression Scale was significantly predictive of psychiatric diagnoses at follow-up. 6 Heightened awareness of this facilitates early diagnosis and the use of appropriate interventions. 7 In the medically ill, early manifestations of delirium may be mistaken for anxiety or depression. These disorders should be considered among the differential diagnoses in individuals who present with depressive symptoms.
Because of the common underrecognition and undertreatment of depression in people with cancer, screening tools can be used to prompt further assessment. 17 Among the physically ill, in general, instruments used to measure depression have not been shown to be more clinically useful than an interview and a thorough examination of mental status. Simply asking the patient whether he or she is depressed may improve the identification of depression.
One study of women with newly diagnosed breast cancer (n = 236) successfully utilized brief screening instruments such as the Distress Thermometer and the Patient Health Questionnaire (PHQ-9) to identify women requiring further assessment to detect clinically significant levels of distress and psychiatric symptoms. 29
In a study of 321 women with newly diagnosed stage I to stage III breast cancer, the ability of the single-item Distress Thermometer to specifically predict depression, as measured by a self-report questionnaire of the nine Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) symptoms for major depressive disorder, was investigated. Sensitivity and specificity characteristics were evaluated, and the optimal cutoff score of 7 was identified, resulting in a sensitivity of 0.81 and a specificity of 0.85 for detecting depression. Therefore, individuals scoring 7 or above should undergo a more thorough psychosocial evaluation. 30
A modification of the Distress Thermometer, the Impact Thermometer, to be used in combination with the Distress Thermometer, has improved specificity for the detection of adjustment disorders and/or major depression, as compared with the Distress Thermometer. The revised tool has a screening performance comparable to that of the Hospital Anxiety and Depression Scale and is brief, potentially making it an effective tool for routine screening in oncology settings. 31 The Mood Evaluation Questionnaire, a cognitive-based screening tool for depression, has moderate correlation with the structured clinical interview for DSM-III-R and good acceptability in the palliative care population. With further validation, it may become a useful alternative in this population because it can be used by clinicians who are not trained in psychiatry. 32
It is important that screening instruments be validated in cancer populations and used in combination with structured diagnostic interviews. 33 A pilot study of 25 patients used a simple, easily reproduced visual analog scale suggesting the benefits to a single-item approach to screening for depression. This scale consists of a 10-cm line with a sad face at one end and a happy face at the other end, on which patients make a mark to indicate their mood. Although the results do suggest that a visual analog scale may be useful as a screening tool for depression, the small patient numbers and lack of clinical interviews limit conclusions. Furthermore, although very high correlations with the Hospital Anxiety and Depression Scale were reported (r = 0.87), no indication of cut-offs was given. Finally, it should be emphasized that such a tool is intended to suggest the need for further professional assessment. However, if validated further, this simple approach could greatly enhance assessment and management of depression in cognitively intact advanced cancer patients. 7 34 Other brief assessment tools for depression can be used. To help patients distinguish normal anxiety reactions from depression, assessment should include discussion about common symptoms experienced by cancer patients. Depression should be reassessed over time. 35 Because of the increased risk of adjustment disorders and major depression in cancer patients, routine screening with increased vigilance at times of increased stress (e.g., diagnosis, recurrences, progression) is recommended. General risk factors for depression are noted in the list above. Other risk factors may pertain to specific populations, for example, patients with head and neck cancer 4 and women at high risk for the development of breast cancer. 36
|How well are you coping with your cancer? Well? Poorly?||Well-being|
|How are your spirits since diagnosis? During treatment? Down? Blue?||Mood|
|Do you cry sometimes? How often? Only alone?||Mood|
|Are there things you still enjoy doing, or have you lost pleasure in things you used to do before you had cancer?||Anhedonia|
|How does the future look to you? Bright? Black?||Hopelessness|
|Do you feel you can influence your care, or is your care totally under others' control?||Helplessness|
|Do you worry about being a burden to family/friends during cancer treatment?||Guilt|
|Do you feel others might be better off without you?||Worthlessness|
|Physical symptoms (evaluate in the context of cancer-related symptoms)|
|Do you have pain that isn't controlled?||Pain|
|How much time do you spend in bed?||Fatigue|
|Do you feel weak? Fatigue easily? Rested after sleep? Any relationship between how you feel and a change in treatment or how you otherwise feel physically?||Fatigue|
|How is your sleeping? Trouble going to sleep? Awake early? Often?||Insomnia|
|How is your appetite? Food tastes good? Weight loss or gain?||Appetite|
|How is your interest in sex? Extent of sexual activity?||Libido|
|Do you think or move more slowly than usual?||Psychomotor slowing|
Organic Mood Syndromes or Mood Syndromes Related to Medical Condition (MSRMC), as they are now referred to in the Diagnostic and Statistical Manual for Mental Disorders, 4th Edition (DSM-IV), often mimic the mood syndromes in their presentation. The assumption is made (perhaps based on their time course or laboratory data) that an organic or medical factor has a role in the etiology of the syndrome. The DSM-IV suggests that prominent cognitive abnormalities may be accompanying factors and therefore are useful in making the diagnosis. The DSM-IV also highlights profound apathy as a sign of MSRMC. Consideration should be given to obtaining laboratory data to assist in detection of electrolyte or endocrine imbalances or the presence of nutritional deficiencies. Clinical experience suggests that pharmacotherapy is more advantageous than psychotherapy alone in the treatment of depression that is caused by medical factors, particularly if the dosages of the causative agent(s) (i.e., steroids, antibiotics, or other medications) cannot be decreased or discontinued. 38
To make a diagnosis of depression, the clinician should confirm that these symptoms will have lasted a minimum of 2 weeks and are present on most days. The diagnosis of depression in people with cancer can be difficult due to the problems inherent in distinguishing biological or physical symptoms of depression from symptoms of illness or toxic side effects of treatment. This is particularly true of individuals who are receiving active treatment or those with advanced disease. Cognitive symptoms such as guilt, worthlessness, hopelessness, thoughts of suicide, and loss of pleasure in activities are probably the most useful in diagnosing depression in people with cancer. One German study comparing cancer patients who had a current affective disorder with those who had a single depressive symptom found loss of interest, followed by depressed mood, to yield the highest power of discrimination between the two groups on multivariate analysis. 43
The evaluation of depression in people with cancer should also include a careful assessment of the person's perception of the illness, medical history, personal or family history of depression or thoughts of suicide, current mental status, and physical status, as well as treatment and disease effects, concurrent life stressors, and availability of social supports. It is important to understand that more than 90% of patients indicate that they prefer to discuss emotional issues with their physician, but over one quarter of patients feel that the physician must initiate any discussion of that topic. 44 Suicidal ideation, when it occurs, is frightening for the individual, the health professional, and the family. Suicidal statements may range from an offhand comment resulting from frustration or disgust with a treatment course: If I have to have one more bone marrow aspiration this year, I'll jump out the window, to a reflection of significant despair and an emergent situation: I can no longer bear what this disease is doing to all of us, and I am going to kill myself. Exploring the seriousness of the thoughts is imperative. If the suicidal thoughts are believed to be serious, a referral to a psychiatrist or psychologist should be made immediately and attention should be given to the patient's safety. Additional information on suicide can be found in the Suicide Risk in Cancer Patients section.
The most common form of depressive symptomatology in people with cancer is an adjustment disorder with depressed mood, sometimes referred to as reactive depression. This disorder is manifested when a person has a dysphoric mood that is accompanied by the inability to perform usual activities. 45[Level of evidence: II] The symptoms appear to be prolonged and in excess of a normal and expected reaction but do not meet the criteria for a major depressive episode. When these symptoms significantly interfere with a person's daily functioning, such as attending to work or school activities, shopping, or caring for a household, they should be treated in the same way that major depression is treated (i.e., consider using crisis intervention, supportive psychotherapy, and medication, especially with drugs that quickly relieve distressing symptoms). Basing the diagnosis on these symptoms can be problematic when the individual has advanced disease and the illness itself is undermining functioning. It is also important to distinguish between fatigue and depression, which are often interrelated. The different mechanisms that give rise to these conditions can be treated separately. 1 In more advanced illness, focusing on despair, guilty thoughts, and a total lack of enjoyment of life is helpful in diagnosing depression. (Refer to the PDQ® summary on Adjustment to Cancer: Anxiety and Distress for further information.)
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