ABSTRACT: Depression is a common complication of cancer, occurring in about 25% of all patients. If left untreated, depression can contribute to poor treatment compliance, increased hospital stays, and mortality. Medical issues, as well as psychosocial stressors, can complicate the diagnosis of depression in people with cancer. This article describes the clinical presentation of depression in cancer patients, reviews the differential diagnosis, and discusses various treatment options, including antidepressants. [ONCOLOLOGY 13(9):1293-1301, 1999]
An estimated 25% of all cancer patients will experience major depression at some point in their illness.[1-5] People with cancer are three times more likely than the general population and almost two times more likely than other hospitalized medical patients to develop major depression.[6,7] The prevalence of depression is even higher in cancer patients with the greatest disability and distressing physical symptoms, especially uncontrolled pain.
Because many clinicians believe that they themselves would be depressed if they had cancer, depression is sometimes viewed as being “appropriate” in cancer patients. However, it is never appropriate for cancer patients to suffer with significant depression. Cassem notes that although massive bleeding is an “appropriate” sequela of a ruptured spleen, it is unthinkable to just stand by and allow a patient to bleed to death.
Similarly, depression is treatable. Untreated, it can lead to decreased compliance with medical care, prolonged hospital stays, and increased morbidity and, possibly, mortality.[9-11] Some patients who are depressed are more likely to request euthanasia or physician-assisted suicide; depressed cancer patients are more likely to commit suicide than other depressed patients.[12,13]
Given the seriousness of depression, it is important for caregivers to recognize and treat it. Past studies have shown that oncologists and primary care providers have difficulty recognizing depressive symptoms in cancer patients.[14,15] Major depression is a clinical entity with specific signs, symptoms, and treatments. It is more than just sadness. Just as one would not immediately diagnose pneumonia in a patient who has a cough, a patient who is crying may not necessarily have a major depressive episode.
The two major diagnoses for significant depressive symptoms are adjustment disorder (reactive depression) and major depression. When mental health professionals diagnose depressive syndromes, they usually use the criteria set forth in the fourth edition of the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders (DSM IV). As shown in Table 1, the DSM IV defines major depression as having at least five of the following symptoms ³ 2 weeks: (1) depressed mood most of the day; (2) loss of interest or pleasure; (3) change in appetite and/or change in weight; (4) insomnia or hypersomnia; (5) psychomotor retardation or agitation; (6) loss of energy; (7) feelings of worthlessness or guilt; (8) poor concentration; and (9) thoughts of death or suicidal ideation. Referred to as the “neurovegetative symptoms” of depression, some of these symptoms are related to bodily functions.
In order to meet the criteria for major depression, one of the patient’s symptoms must be either depressed mood or loss of interest/pleasure, and the individual must also be experiencing distress or impairment in social, occupational, or other important areas of functioning. Major depression is usually distinguished from an adjustment disorder by the degree, duration, or amount of symptoms.
Making the diagnosis of depression can be more complicated in cancer patients, however. Many of the neurovegetative symptoms of depression— especially loss of energy, loss of appetite, and sleep disturbance—overlap with common symptoms of cancer or other medical illnesses, and with side effects of medical treatments used in cancer patients.
Because these criteria may not be specific for depression in medical illnesses, a set of psychological criteria is often used in their place. Endicott suggested substituting the psychological symptoms of self-pity, brooding, crying spells, and pessimism for the neurovegetative symptoms. Some clinicians highlight the importance of the cognitive symptoms of depression, such as depressed thoughts, hopelessness about appreciating any degree of quality in their lives, guilt or worthlessness, or persistent suicidal ideation. It is important to remember that someone who is acutely dying often becomes withdrawn and hypoactive and may exhibit neurovegetative symptoms. This is usually part of the dying process, not an episode of major depression.
Since depression is both prevalent and treatable in cancer patients, caregivers should routinely screen patients for its presence. Several predisposing factors have been correlated with the development of depression in cancer patients. These include a history of psychiatric illness, early maladjustment to cancer, poor social support, and low performance status.
Assessment for depression with a rapid mental status examination is feasible and should be done in the context of a regular medical visit. Using the questions listed in Table 2, the clinician can rapidly (ie, within 5 to 10 minutes) assess the patient for depression. Three areas should be assessed: (1) the patient’s mood, (2) physical signs of depression (which must be evaluated clinically to determine whether fatigue, insomnia, and low libido are caused by depression or by the cancer or cancer treatment), and (3) the severity of depression.
Suicidal risk must also be assessed, as patients do not readily discuss suicidal thoughts with their caregivers. The clinician should explore how serious the thoughts are and whether the individual has personal factors (ie, prior psychiatric disorder, particularly depression or substance abuse; recent bereavement; and/or few social supports) or medical factors (ie, poorly controlled pain, advanced stage of disease with debilitation, mild delirium with poor impulse control, and/or hopelessness or helplessness in the context of depression) that may contribute to the depression. These risk factors for suicide are summarized in Table 3.
If suicidal ideation is present, a psychiatrist should be asked to evaluate the patient. If the individual appears to be at high risk, he or she should be sent to an emergency room for evaluation and possible hospitalization.
In a busy practice where this type of questioning may seem too time-consuming to ask of all patients routinely, screening tools could be given to patients in the waiting room for quick, timely assessment. Patients who report some depressive symptoms or distress on those screening instruments could be evaluated further in an interview.
Some screening tools used in oncology settings include the Hospital Anxiety and Depression Scale (HADS), Primary Care Evaluation of Mental Disorders (PRIME-MD), and the Zung Self-Rating Depression Scale.[20-22]. Memorial Sloan-Kettering Cancer Center has been using a one-item, rapid screening tool, the “distress thermometer,” that has been easily completed by patients in clinic waiting rooms.
One interesting study found that the one question that correlated most highly with the presence of major depression in terminally ill patients was simply, “Are you depressed?” This single-item screening tool outperformed questionnaires and other screening tools for the eventual diagnostic outcome of evaluations.
Once depressive symptoms have been identified, the clinician should eliminate other possible diagnoses besides major depression. Symptoms typically associated with depression can be seen with other situations related to cancer. This section reviews common medical problems and psychiatric disorders that must be considered and ruled out before diagnosing major depressive disorder in a cancer patient.
Reaction to Bad News—When confronted initially with a diagnosis of cancer, most patients experience a short period of shock, such that the diagnosis may actually be disbelieved for several days. The second phase that follows is characterized by more visible distress: sadness, depressed mood, anxiety, anorexia, insomnia, and irritability that may last up to 2 weeks. There is a sense of sadness and uncertainty about the future, and patients’ thoughts often are preoccupied with illness, death, and anticipated losses. All of these feelings are normal at this time. Some patients cannot carry out daily activities and have trouble processing information and concentrating.
Within a few weeks, however, most patients have adapted to the new reality, and symptoms resolve, usually as treatment is undertaken and optimism about the future begins to return. This is not a major depressive episode. Committing a person in this situation to a long course of antidepressants for symptoms that are usually limited in duration to a few weeks is not beneficial to the patient and only increases the risk of drug-induced side effects. Support from oncologists and nurses or brief psychotherapy, on the other hand, can be helpful.
The same series of reactive depressive symptoms can recur at transition points in the illness that carry a negative connotation: ie, notification of failed or failing treatment results; evidence of continued disease on bone marrow aspirate; development of graft-vs-host disease; or evidence of disease progression or relapse. Debilitating symptoms, such as recurrent nadir fevers, a new significant pain, or severe, continuous nausea and vomiting, can also engender feelings of despair and an inability to cope.
These normal responses are usually adequately addressed by listening to the patient’s concerns, acknowledging their appropriateness, explaining the situation, and offering reassurance about treatment. This support, called “normalizing” feelings, is helpful as the physician validates the legitimacy of the patient’s distress.
Physical Illness—As noted above, it is important to try to distinguish between symptoms resulting from the medical illness and neurovegetative symptoms of depression. If the diagnosis is still in question after applying the Endicott substitution criteria, it may be beneficial to institute a trial of antidepressant therapy to see whether symptoms improve.
Adjustment Disorder—When a patient has significant depressive symptoms that develop after an identifiable stressor, such as a cancer diagnosis or recurrence, but does not fully meet the criteria for a major depressive episode, a diagnosis of adjustment disorder is made. If symptoms are severe or prolonged enough, a trial of antidepressants may be beneficial. Sometimes an adjustment disorder can progress into a major depressive episode.
Medical Causes of Depressive Symptoms—Many aspects of medical illnesses, including the disease itself, metabolic abnormalities, treatments, and medications for the illness, can lead to depressive symptoms. Because the depression is the direct result of medical illness, psychiatrists technically call it a mood disorder secondary to a medical condition. Treatment in such cases would first focus on correcting the medical problem, but psychiatric interventions, such as antidepressants, anxiolytics, and hypnotics, would also be employed.
Pain—Several common medical conditions and medications can produce mild to severe depressive symptoms (Table 4). The most common cause of depressed mood in cancer patients is uncontrolled pain. It is accompanied by anxiety and a sense of anguish that life is intolerable unless the pain is relieved. Relief of the pain, or even acknowledgment of its existence and an attempt to relieve it, often leads to an improvement in depressive symptoms.
Metabolic and Endocrinologic Abnormalities—Metabolic abnormalities that can alter mood include hypercalcemia, related to either bone metastases or a neuroendocrine effect of the tumor; potassium and sodium imbalances; anemia; and vitamin B12 deficiency. Endocrinologic abnormalities that should be looked for include hyperthyroidism or hypothyroidism, Cushing’s syndrome, hyperparathyroidism, and adrenal insufficiency. Depression occurs with greater frequency and severity in patients with pancreatic cancer, although the mechanism is not fully understood.
Neurologic problems can also mimic or produce depression. Depressive symptoms can be seen with primary central nervous system lesions or brain metastases, particularly right-sided or frontal lesions. Neurologic problems unrelated to cancer, such as cerebral vascular disease, Parkinson’s disease, and Huntington’s disease, have also been known to produce depression.
Drugs Used in Cancer Treatment—Medications commonly used in cancer treatment can also cause depressive symptoms. The glucocorticosteroids, prednisone and dexamethasone frequently cause alterations in mood, which range from euphoria to irritability to severe depression, as well as delirium and psychosis. Interferon-alfa (Intron A, Roferon-A) and interleukin-2 (aldesleukin [Proleukin]), which are also frequently given to cancer patients, may cause depressive symptoms, as well as cognitive deficits.
Although a significant number of chemotherapeutic agents are known to have potentially severe side effects, relatively few of these drugs cause depression. Those that do are vincristine, vinblastine, and asparaginase (Elspar). Procarbazine (Matulane), ironically a mild monoamine oxidase inhibitor, also has been reported to cause depression. Other medications, such as methyldopa, reserpine, barbiturates, benzodiazepines, propranolol, and some antibiotics, such as amphotericin B, can cause depressive symptoms as well.
Often, a reduction in the dose or discontinuation of the causative medication will reduce the depressive symptoms. However, if the dose cannot be tapered, antidepressant therapy may be necessary.
Delirium may present with such symptoms as depressed mood and crying. However, patients with delirium manifest a waxing and waning course of attentional and cognitive disturbances and also experience hallucinations, usually visual. Depression can sometimes have psychotic features, but hallucinations are not typically visual. Moreover, unlike depression, delirium develops over a relatively short period.
Dementia—When patients have difficulty with memory and concentration, it may be difficult to tell whether the symptoms are due to dementia or major depression. A thorough medical evaluation, along with a cognitive examination, such as the Mini-Mental Status Examination, should be done. The history, including the onset, time course of depressive and cognitive symptoms, course of illness, and responses to treatment, is often helpful in making this determination. In patients with dementia, there is usually a history of slowly declining cognitive function, whereas in those with major depressive episode, there is usually an abrupt onset of cognitive difficulties associated with the depression.
Neuropsychological testing may be helpful in distinguishing between dementia and the pseudodementia of depression. Depressed patients are usually able to do the cognitive tasks with significant coaxing and motivation.
Bipolar Disorder—It is important to ask the patient about any personal history of manic episodes or a family history of bipolar disorder (ie, symptoms of episodic euphoria, grandiosity, increased energy and physical activity despite sleeplessness, spending sprees, or hypersexuality), as the treatments for depression and bipolar disorder differ. Antidepressants may actually exacerbate the mood of a bipolar patient. Mood stabilizers are the treatment of choice and referral to a psychiatrist is suggested.
Personality Disorders—The experience of cancer can often exacerbate preexisting coping abilities in patients with personality disorders. Patients with personality disorders, particularly borderline personality disorder, describe lifelong histories of depression and long-standing patterns of intense, conflictual relationships, self-destructive behaviors, and chronic feelings of emptiness. They may, however, also experience a comorbid episode of depression and require psychotropic medication.
Patients with personality disorders are frequently the most difficult to manage, and nonmedical interventions are often most useful. These include having regularly scheduled visits; establishing good communication between all caregivers to prevent the pitting of one caregiver against another; setting limits on behaviors; and sometimes having a designated coordinator of care.
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