Symptoms and Risk Factors
Screening and Assessment for Depression
        Clinical interview
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.
• Fatigue.[1]
• 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 the Suggested Questions For the Assessment of Depressive Symptoms in Adults With Cancer table):

• “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.[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, 8 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] For some cancer populations, such as those status-post stem cell transplantation, preliminary data suggest an association between depressive symptoms and survival. If confirmed, diagnosis and treatment of depression may afford an opportunity to impact mortality as well as quality of life.[8] 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.[9,10]
  • Poorly controlled pain.[11]
  • Advanced stage of cancer.[11]
  • Increased physical impairment or discomfort.
  • Pancreatic cancer.[12]
  • Being unmarried and having head and neck cancer.[13]
  • Treatment with certain chemotherapeutic agents:
    • Corticosteroids.
    • Procarbazine.
    • L-Asparaginase.
    • Interferon-alfa.[14,3]
    • Interleukin-2.[15,14,3]
    • Amphotericin-B.



• 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.[9]
  • Additional concurrent life stressors.[16]
  • Family history of depression or suicide.
  • Previous suicide attempts.
  • History of alcoholism or drug abuse.
  • Concurrent illnesses that produce depressive symptoms (i.e., stroke or myocardial infarction).
  • Past treatment for psychological problems.[17]

Because of the common underrecognition and undertreatment of depression in people with cancer, screening tools can be used to prompt further assessment.[18] 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. 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?”[19] 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.[20] Other screening tools that have been used and validated in cancer populations include the Hospital Anxiety and Depression Scale,[21] the Psychological Distress Inventory,[22] and the Edinburgh Depression Scale.[23] The Hospital Anxiety and Depression Scale may have limited utility in certain patient populations such as early-stage breast cancer [24] and palliative care.[25,26] The Brief Symptom Inventory, the Zung Self-Rating Depression Scale, and the Distress Thermometer are commonly used screening tools.[27-29] 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.[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.[34,7] 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 (i.e., diagnosis, recurrences, progression) is recommended. General risk factors for depression are noted in the list above. Other risk factors may pertain to specific populations, i.e., patients with head and neck cancer [4] and women at high risk for the development of breast cancer.[36]

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]

Possible Medical Causes of Depressive Symptoms in People With Cancer*

• Uncontrolled pain.[11]
• Metabolic abnormalities:
  • Hypercalcemia.
  • Sodium/potassium imbalance.
  • Anemia.
  • Vitamin B12 or folate deficiency.
  • Fever.
• Endocrine abnormalities:
  • Hyperthyroidism or hypothyroidism.
  • Adrenal insufficiency.
• Medications:[15,39-41,3]
  • Steroids.
  • Endogenous and exogenous cytokines, i.e., interferon-alfa and aldesleukin (interleukin-2, IL-2).[42]
  • Methyldopa.
  • Reserpine.
  • Barbiturates.
  • Propranolol.
  • 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.[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] 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 Normal Adjustment and the Adjustment Disorders for further information.)

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