Assessment and Diagnosis
Symptoms and Risk Factors
The symptoms of major depression are as follows:
- A depressed mood for most of the day and on most days.
- Diminished pleasure or interest in most activities.
- Significant change in appetite and sleep patterns.
- Psychomotor agitation or slowing.
- Feelings of worthlessness or excessive, inappropriate guilt.
- Poor concentration.
- Recurrent thoughts of death or suicide.
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):
- “Many people find themselves dwelling on thoughts about their cancer. What kinds of thoughts do you have?”
- “Do you find yourself ever thinking I brought this on myself, God is punishing me? How often? Only a few times a week, or all the time? Do you believe these thoughts are true?”
- “In spite of these thoughts, are you still able to go on with your life and find pleasure in things? Or, are you so preoccupied that you can't sleep, or feel hopeless?”
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. 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. 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. Heightened awareness of this facilitates early diagnosis and the use of appropriate interventions. 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.
Risk Factors for Depression in People With Cancer
- Cancer-related risk factors:
- Depression at time of cancer diagnosis.[8,9]
- Poorly controlled pain.
- Advanced stage of cancer.
- Increased physical impairment or discomfort.
- Pancreatic cancer.
- Being unmarried and having head and neck cancer.
- Treatment with certain chemotherapeutic agents:
- Noncancer-related risk factors:
- History of depression:
- Two or more episodes in a lifetime.
- First episode early or late in life.
- Lack of family support.
- Additional concurrent life stressors.
- Family history of depression or suicide.
- Previous suicide attempts.
- History of alcoholism or drug abuse.
- Concurrent illnesses that produce depressive symptoms (e.g., stroke or myocardial infarction).
- Past treatment for psychological problems.
- History of depression:
Because of the common underrecognition and undertreatment of depression in people with cancer, screening tools can be used to prompt further assessment. 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.
The following screening tools are commonly used:
- A single-item interview. In persons with advanced cancer, a single-item interview question has been found to have acceptable psychometric properties and can be useful. One example is to ask “Are you depressed?” Another example is to say, “Please grade your mood during the past week by assigning it a score from 0 to 100, with a score of 100 representing your usual relaxed mood.” A score of 60 is considered a passing grade.
- The Hospital Anxiety and Depression Scale. The Hospital Anxiety and Depression Scale may have limited utility in certain patient populations such as early-stage breast cancer  and palliative care.[22,23]
- The Psychological Distress Inventory.
- The Edinburgh Depression Scale.
- The Brief Symptom Inventory.
- The Zung Self-Rating Depression Scale.
- The Distress Thermometer.
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.
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.
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. 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.
It is important that screening instruments be validated in cancer populations and used in combination with structured diagnostic interviews. 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. 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  and women at high risk for the development of breast cancer.Clinical interview
Table 1. Suggested Questions for the Assessment of Depressive Symptoms in Adults With Cancera
|aAdapted from Roth et al.|
|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.
Possible Medical Causes of Depressive Symptoms in People With Cancer*
- Uncontrolled pain.[Level of evidence: II]
- Metabolic abnormalities:
- Sodium/potassium imbalance.
- Vitamin B12 or folate deficiency.
- Endocrine abnormalities:
- Hyperthyroidism or hypothyroidism.
- Adrenal insufficiency.
- Medications:[Level of evidence: I][39-41];[Level of evidence: II]
- Endogenous and exogenous cytokines, i.e., interferon-alfa and aldesleukin (interleukin-2 [IL-2]).
- Some antibiotics (e.g., amphotericin B).
- Some chemotherapeutic agents (e.g., procarbazine, L-asparaginase).
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.
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. 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.[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. 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.)References
- Jacobsen PB, Donovan KA, Weitzner MA: Distinguishing fatigue and depression in patients with cancer. Semin Clin Neuropsychiatry 8 (4): 229-40, 2003. [PUBMED Abstract]
- De Leeuw JR, De Graeff A, Ros WJ, et al.: Negative and positive influences of social support on depression in patients with head and neck cancer: a prospective study. Psychooncology 9 (1): 20-8, 2000 Jan-Feb. [PUBMED Abstract]
- Capuron L, Ravaud A, Neveu PJ, et al.: Association between decreased serum tryptophan concentrations and depressive symptoms in cancer patients undergoing cytokine therapy. Mol Psychiatry 7 (5): 468-73, 2002. [PUBMED Abstract]
- de Leeuw JR, de Graeff A, Ros WJ, et al.: Prediction of depression 6 months to 3 years after treatment of head and neck cancer. Head Neck 23 (10): 892-8, 2001. [PUBMED Abstract]
- Paice JA: Managing psychological conditions in palliative care. Am J Nurs 102 (11): 36-42; quiz 43, 2002. [PUBMED Abstract]
- Akechi T, Okuyama T, Sugawara Y, et al.: Major depression, adjustment disorders, and post-traumatic stress disorder in terminally ill cancer patients: associated and predictive factors. J Clin Oncol 22 (10): 1957-65, 2004. [PUBMED Abstract]
- Passik SD, Kirsh KL, Theobald D, et al.: Use of a depression screening tool and a fluoxetine-based algorithm to improve the recognition and treatment of depression in cancer patients. A demonstration project. J Pain Symptom Manage 24 (3): 318-27, 2002. [PUBMED Abstract]
- Nordin K, Glimelius B: Predicting delayed anxiety and depression in patients with gastrointestinal cancer. Br J Cancer 79 (3-4): 525-9, 1999. [PUBMED Abstract]
- Karnell LH, Funk GF, Christensen AJ, et al.: Persistent posttreatment depressive symptoms in patients with head and neck cancer. Head Neck 28 (5): 453-61, 2006. [PUBMED Abstract]
- Ciaramella A, Poli P: Assessment of depression among cancer patients: the role of pain, cancer type and treatment. Psychooncology 10 (2): 156-65, 2001 Mar-Apr. [PUBMED Abstract]
- Green AI, Austin CP: Psychopathology of pancreatic cancer. A psychobiologic probe. Psychosomatics 34 (3): 208-21, 1993 May-Jun. [PUBMED Abstract]
- Kugaya A, Akechi T, Okuyama T, et al.: Prevalence, predictive factors, and screening for psychologic distress in patients with newly diagnosed head and neck cancer. Cancer 88 (12): 2817-23, 2000. [PUBMED Abstract]
- Capuron L, Ravaud A, Gualde N, et al.: Association between immune activation and early depressive symptoms in cancer patients treated with interleukin-2-based therapy. Psychoneuroendocrinology 26 (8): 797-808, 2001. [PUBMED Abstract]
- Capuron L, Ravaud A, Dantzer R: Early depressive symptoms in cancer patients receiving interleukin 2 and/or interferon alfa-2b therapy. J Clin Oncol 18 (10): 2143-51, 2000. [PUBMED Abstract]
- Green BL, Krupnick JL, Rowland JH, et al.: Trauma history as a predictor of psychologic symptoms in women with breast cancer. J Clin Oncol 18 (5): 1084-93, 2000. [PUBMED Abstract]
- Burgess CC, Ramirez AJ, Richards MA, et al.: Does the method of detection of breast cancer affect subsequent psychiatric morbidity? Eur J Cancer 38 (12): 1622-5, 2002. [PUBMED Abstract]
- Passik SD, Dugan W, McDonald MV, et al.: Oncologists' recognition of depression in their patients with cancer. J Clin Oncol 16 (4): 1594-600, 1998. [PUBMED Abstract]
- Chochinov HM, Wilson KG, Enns M, et al.: "Are you depressed?" Screening for depression in the terminally ill. Am J Psychiatry 154 (5): 674-6, 1997. [PUBMED Abstract]
- Akizuki N, Akechi T, Nakanishi T, et al.: Development of a brief screening interview for adjustment disorders and major depression in patients with cancer. Cancer 97 (10): 2605-13, 2003. [PUBMED Abstract]
- Zigmond AS, Snaith RP: The hospital anxiety and depression scale. Acta Psychiatr Scand 67 (6): 361-70, 1983. [PUBMED Abstract]
- Love AW, Kissane DW, Bloch S, et al.: Diagnostic efficiency of the Hospital Anxiety and Depression Scale in women with early stage breast cancer. Aust N Z J Psychiatry 36 (2): 246-50, 2002. [PUBMED Abstract]
- Lloyd-Williams M, Friedman T, Rudd N: An analysis of the validity of the Hospital Anxiety and Depression scale as a screening tool in patients with advanced metastatic cancer. J Pain Symptom Manage 22 (6): 990-6, 2001. [PUBMED Abstract]
- Lloyd-Williams M, Spiller J, Ward J: Which depression screening tools should be used in palliative care? Palliat Med 17 (1): 40-3, 2003. [PUBMED Abstract]
- Morasso G, Costantini M, Baracco G, et al.: Assessing psychological distress in cancer patients: validation of a self-administered questionnaire. Oncology 53 (4): 295-302, 1996 Jul-Aug. [PUBMED Abstract]
- Lloyd-Williams M, Riddleston H: The stability of depression scores in patients who are receiving palliative care. J Pain Symptom Manage 24 (6): 593-7, 2002. [PUBMED Abstract]
- Derogatis LR, Melisaratos N: The Brief Symptom Inventory: an introductory report. Psychol Med 13 (3): 595-605, 1983. [PUBMED Abstract]
- Dugan W, McDonald MV, Passik SD, et al.: Use of the Zung Self-Rating Depression Scale in cancer patients: feasibility as a screening tool. Psychooncology 7 (6): 483-93, 1998 Nov-Dec. [PUBMED Abstract]
- Roth AJ, Kornblith AB, Batel-Copel L, et al.: Rapid screening for psychologic distress in men with prostate carcinoma: a pilot study. Cancer 82 (10): 1904-8, 1998. [PUBMED Abstract]
- Hegel MT, Moore CP, Collins ED, et al.: Distress, psychiatric syndromes, and impairment of function in women with newly diagnosed breast cancer. Cancer 107 (12): 2924-31, 2006. [PUBMED Abstract]
- Hegel MT, Collins ED, Kearing S, et al.: Sensitivity and specificity of the Distress Thermometer for depression in newly diagnosed breast cancer patients. Psychooncology 17 (6): 556-60, 2008. [PUBMED Abstract]
- Akizuki N, Yamawaki S, Akechi T, et al.: Development of an Impact Thermometer for use in combination with the Distress Thermometer as a brief screening tool for adjustment disorders and/or major depression in cancer patients. J Pain Symptom Manage 29 (1): 91-9, 2005. [PUBMED Abstract]
- Meyer HA, Sinnott C, Seed PT: Depressive symptoms in advanced cancer. Part 1. Assessing depression: the Mood Evaluation Questionnaire. Palliat Med 17 (7): 596-603, 2003. [PUBMED Abstract]
- Lynch ME: The assessment and prevalence of affective disorders in advanced cancer. J Palliat Care 11 (1): 10-8, 1995 Spring. [PUBMED Abstract]
- Lees N, Lloyd-Williams M: Assessing depression in palliative care patients using the visual analogue scale: a pilot study. Eur J Cancer Care (Engl) 8 (4): 220-3, 1999. [PUBMED Abstract]
- Patrick DL, Ferketich SL, Frame PS, et al.: National Institutes of Health State-of-the-Science Conference Statement: Symptom Management in Cancer: Pain, Depression, and Fatigue, July 15-17, 2002. J Natl Cancer Inst 95 (15): 1110-7, 2003. [PUBMED Abstract]
- Wellisch DK, Lindberg NM: A psychological profile of depressed and nondepressed women at high risk for breast cancer. Psychosomatics 42 (4): 330-6, 2001 Jul-Aug. [PUBMED Abstract]
- Roth AJ, Holland JC: Psychiatric complications in cancer patients. In: Brain MC, Carbone PP, eds.: Current Therapy in Hematology-Oncology. 5th ed. St. Louis, Mo: Mosby-Year Book, Inc., 1995, pp 609-18.
- Breitbart W, Holland JC: Psychiatric complications of cancer. Current Therapy in Hematology-Oncology 3: 268-74, 1988.
- Cancer chemotherapy. Med Lett Drugs Ther 29 (736): 29-36, 1987. [PUBMED Abstract]
- Drugs of choice for cancer chemotherapy. Med Lett Drugs Ther 33 (840): 21-8, 1991. [PUBMED Abstract]
- Drugs that cause psychiatric symptoms. Med Lett Drugs Ther 31 (808): 113-8, 1989. [PUBMED Abstract]
- Menzies H, Chochinov HM, Breitbart W: Cytokines, cancer and depression: connecting the dots. J Support Oncol 3 (1): 55-7, 2005 Jan-Feb. [PUBMED Abstract]
- Reuter K, Raugust S, Bengel J, et al.: Depressive symptom patterns and their consequences for diagnosis of affective disorders in cancer patients. Support Care Cancer 12 (12): 864-70, 2004. [PUBMED Abstract]
- Detmar SB, Aaronson NK, Wever LD, et al.: How are you feeling? Who wants to know? Patients' and oncologists' preferences for discussing health-related quality-of-life issues. J Clin Oncol 18 (18): 3295-301, 2000. [PUBMED Abstract]
- Nordin K, Wasteson E, Hoffman K, et al.: Discrepancies between attainment and importance of life values and anxiety and depression in gastrointestinal cancer patients and their spouses. Psychooncology 10 (6): 479-89, 2001 Nov-Dec. [PUBMED Abstract]