Current Management of Depression in Cancer Patients

Depression is a relatively common but regrettably underdiagnosed condition among cancer patients. Comprehensive care should, however, encompass not only a good understanding of the physical domains of patient care, but include attentiveness to the psychological, spiritual, and existential concerns of patients facing malignant illness. Depression can influence a patient’s will to live, as well as diminish the quality and perceived meaning of life. Therefore, health-care staff who care for patients with cancer—particularly patients nearing the terminal phase of their cancer—must be aware of the impact of depression on the patient’s sense of meaning and desire to go on living in the face of a life-threatening illness.

The underdiagnosis of depression in a cancer treatment or palliative care setting occurs for a variety of related reasons. These include uncertainty as to how to make a diagnosis of depression in medically ill patients, the false assumption that all cancer patients are "understandably depressed," physician discomfort with probing too deeply into the psychological distress of patients, and discomfort in using, or lack of familiarity with, the treatment options available to treat depression.[1,2]

All patients with a life-threatening condition and particularly those with a terminal prognosis will understandably experience some periods of profound sadness. Such a reaction to vulnerability and loss is inherently human. Clinical depression or depressive syndrome, however, may complicate a patient’s cancer illness and is marked by a persistent, prominent sad mood, loss of interest in almost all activities, overwhelming helplessness, hopelessness, worthlessness, feelings of guilt, and preoccupation with thoughts of suicide or death. In addition to these psychological symptoms, people with major depression also experience a variety of physical symptoms including fatigue, poor concentration, anorexia, weight loss, and insomnia.

Not surprisingly, clinical depression may lead some patients to a heightened desire for hastened death. Studies of terminally ill patients and ambulatory AIDS patients have demonstrated that the most significant predictor of support for physician-assisted suicide was depression and psychological distress.[3,4] Patients with cancer or other terminal illnesses are at increased risk of suicide, compared to the general population.[5] Suicide risk factors include poorly controlled pain, depression, delirium, and various disabilities resulting from advanced illness. In one study of psychiatric disorders in suicidal cancer patients, 39% were thought to have a major depression, 54% were diagnosed with an adjustment disorder with anxious and/or depressed features, and 20% were delirious.[6]

The elderly are at greater risk for both depression and suicide, due to numerous losses they may experience—loss of good health, financial losses, loss of spouse or friends, and so forth. Depressed elderly patients may not describe themselves as depressed, but instead may complain of loss of interest in activities, or problems with memory or concentration. Careful history-taking will demonstrate that depressive features often antedate these changes.[7]

Depressive symptoms may occur in many patients with advanced cancer, and 10% to 20% of these patients meet diagnostic criteria for major depression.[6,8] One study suggested that the greater the physical disability suffered by the patient, the more likely they were to present with significant depressive symptoms.[9] Physicians must be aware of the possible existence of depression in seriously ill patients, and the effect this may have on their desire for death. Ambivalence or apathy about continued treatment may, in fact, be due to feelings of hopelessness engendered by a clinical depression. As such, there is the risk that these patients will receive less than optimal care, should depression be misperceived as a "normal reaction" to serious physical illness. It is therefore essential for physicians to screen for and treat depression in this patient population.

In this article, we will examine techniques for the assessment of depression in cancer patients, as well as current strategies for the treatment of depression in these patients. A combination of supportive psychotherapy and appropriate pharmacotherapy is the most effective treatment for severe depression; both approaches are discussed, with particular emphasis on their application in the cancer care setting.

Assessment of Depression in Cancer Patients

Case Presentation

Ms. J. is a 48-year-old woman with stage IV breast cancer. She has been married for 17 years and has a 12-year-old daughter. Several months after starting on paclitaxel(Drug information on paclitaxel) and tamoxifen(Drug information on tamoxifen), she discloses the fact that she has been feeling profoundly depressed for nearly a year. She reports feeling depressed most of the time, along with decreased interest in many activities and an avoidance of all social contact. She thinks constantly about death, and no longer sees a point in living. She denies suicidal ideation but states that going to sleep and not waking up would be a welcome relief. She reports significant difficulty with sleep, libido, energy, memory, and concentration.

Upon examination, she cries throughout the consultation, endorsing feelings of helplessness, hopelessness, and worthlessness. She feels she has become a burden to everyone that has contact with her. There is no evidence of delusions or psychosis, but she does seem to have psychomotor retardation. There is also a significant family history of depression (mother, several siblings, and a paternal aunt).

This case presentation illustrates one particular reaction to a diagnosis of advanced cancer. Is this a normal response? While emotional distress is a normal reaction to a cancer diagnosis, profound and unremitting depressed mood, excessive guilt, anhedonia (an inability to experience pleasure), and loss of interest in all activities are not. Patients who are newly diagnosed with cancer and those who learn of a relapse, or that treatment has failed, frequently demonstrate a response marked by a period of initial shock or disbelief. This is often followed by a period of turmoil, marked by symptoms of anxiety and depression, irritability, and sleep and appetite disruption. After a period of several weeks, a tolerable degree of resolution usually occurs.[10]

Symptoms

Depression, as defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV),[11] is characterized by a constellation of symptoms, which must occur at a certain level of severity, for a defined duration, and result in impairment in functional and social roles. There are two core criterion symptoms for major depression in the DSM-IV: depressed mood and anhedonia (a marked loss of interest or pleasure in all activities). In order to qualify for the diagnosis, one of these core symptoms must be consistently present for a minimum of 2 weeks, along with at least four other symptoms from the DSM-IV depression symptom list. In the severely ill, however, symptoms such as fatigue, reduced appetite, weight loss, sleep problems, and poor concentration may not be helpful in making the diagnosis of major depression, as these symptoms can be caused by the patient’s underlying medical illness.[12]

Screening

Despite the nonspecificity of these somatic symptoms, we have reported that asking patients if they are feeling depressed "most of the time" is a very simple and effective way to screen for clinical depression. Recent work has compared various brief screening measures for depression in terminally ill patients. A single-item screening approach, which essentially asked patients if they felt depressed most of the time, correctly identified the eventual diagnostic outcome of every patient and was superior to other self-report measures for assessing depression. Inclusion of questions concerning loss of interest or pleasure in activities did not improve diagnostic accuracy but might be appropriate in a brief screening interview, as it provides for complete coverage of core depressive symptoms and reduces the possibility of missing the diagnosis.[13]

Organic Causes

Physicians should also consider the possibility of organic mental disorders, which are prevalent in patients with advanced disease and may play a role in the patient’s presentation. Delirium, dementia, anxiety disorders, and organic mood syndromes are easy to mistake for a (functional) psychiatric disturbance. Symptoms such as disbelief, denial, numbness, irritability, hopelessness, and suicidal ideation are found in major depression, anxiety disorders, and adjustment disorders. However, in progressive dementias, the organic nature of the presenting symptoms usually becomes more obvious.

Neuropsychological testing may help distinguish dementia from a depression or an adjustment disorder. Other issues, such as the potential duration of the organic mental syndrome and its effect on competency should also be considered. It has been estimated that approximately 25% of hospitalized medical and surgical patients suffer from dementia, and that the prevalence of delirium in dying patients approaches 80%. Indeed, the magnitude of this problem is compelling.[14]

Risk Factors

Risk factors for depression in patients suffering from cancer include a past personal or family history of depression and/or previous suicide attempts by the patient. Other risk factors include increasing physical disability, which appears to correlate with measures of depression and distress in cancer patients, as well as physical pain. Numerous studies have found an association between increased pain and reports of depression or other psychiatric complications. Spiegel et al found that patients with the highest pain levels were two to four times more likely to be diagnosed with a depressive disorder than patients with lower pain levels.[15] Of note, chronically discomforting pain may cause some patients to become depressed, and conversely, depression may result in an amplification of the pain experience.[6] However, a strong social network has been shown to be a protective factor against depression.[16]

Disease processes that directly affect the central nervous system cause depressive symptoms, although organic mood disorders can also result from disorders with no direct neurologic involvement (eg, Cushing’s syndrome due to pituitary tumors has been linked with depression). Hypercalcemia, which is often associated with breast or lung cancer, has also been associated with depression.[17,18] In addition, patients with oral, pharyngeal, and lung cancers are at increased risk of suicide, possibly because these diseases are often associated with premorbid alcohol(Drug information on alcohol) and substance abuse and may result in profound facial disfigurement and associated impairments.

Pancreatic cancer has been associated with a high prevalence of depressive and suicidal states,[19] ostensibly because of tumor-induced changes in the neuroendocrine system. However, pain, which is common with pancreatic cancer, may also be a causative factor.[20] In addition, the grave prognosis that this illness carries may give rise to depressive illness. Numerous anticancer drugs—including corticosteroids, procarbazine(Drug information on procarbazine) (Matulane), L-asparaginase (Elspar), interferon, vinblastine(Drug information on vinblastine), vincristine, tamoxifen, and cyproterone(Drug information on cyproterone) (Androcur)—have also been associated with depression. Poorly controlled severe nausea and vomiting may also contribute to depression.[10]

A Treatable Illness

Some sadness is inevitable in all patients facing a life-threatening or terminal condition. Clinical depression, on the other hand, is a treatable illness, and physician awareness and assistance can help patients to recover their ability to enjoy social interactions, and sometimes prior interests. Physical symptoms of depression such as poor energy, sleep, and appetite may be relieved. Finally, proper treatment of clinical depression can result in a renewed ability to find meaning in life, despite the uncertain or dire medical circumstances. Practical treatment strategies, and the considerations that underlie these approaches, will be discussed in the next section.