Depression and Anxiety
Kimberly Miller
Mary Jane Massie
Emotional distress is a normal response to a catastrophic event such as the diagnosis of cancer or any other life-threatening medical disease. The diagnosis of cancer induces stresses that are caused by the patient’s perceptions of the disease, its manifestations, and the stigma commonly attached to this disease. For most individuals, the primary fear is a painful death. Patients also fear becoming disabled and dependent, having altered appearance and changed body function, and losing the company of those close to them. Each of these fears is accompanied by a level of psychological distress that varies from patient to patient. This variability is related to medical factors (e.g., site and stage of illness, treatments offered, course of the cancer, and the presence of pain); psychological factors (e.g., prior adjustment, history of losses, coping ability, emotional maturity, the disruption of life goals, and the ability to modify plans); cultural, spiritual and social factors (e.g., availability of emotional support from family, friends, and coworkers); and financial stability (1). Understanding these factors allows the clinician to predict and manage distress that exceeds a threshold arbitrarily defined as normal. The presence of intolerable or prolonged distress that compromises the usual function of the patient requires evaluation, diagnosis, and management.
Normal Responses to the Stress of Cancer
Individuals who receive a diagnosis of cancer, or who learn that relapse has occurred or that treatment has failed, often show a characteristic emotional response: a period of initial shock and disbelief, followed by a period of turmoil with mixed symptoms of anxiety and depression, irritability, and disruption of appetite and sleep. The ability to concentrate and carry out usual daily activities is impaired, and thoughts about the diagnosis and fears about the future may intrude (2). These normal responses to crisis or transitional points in cancer resemble the response to stress associated with other threatened or actual losses.
These symptoms usually resolve over days to weeks with support from family, friends, and a physician who outlines a treatment plan that offers hope. Interventions beyond those provided by physicians, nurses, and social workers are generally not required, unless symptoms of emotional distress interfere with function or are prolonged or intolerable. Prescribing a hypnotic (e.g., zolpidem) for insomnia and anxiolytics (e.g., a benzodiazepine, such as alprazolam or lorazepam) to reduce anxiety can help the patient through this crisis period.
Some patients continue to have high levels of depression and anxiety (both are usually present, although one may predominate) that persist for weeks or months. This persistent reactive distress is not adaptive, often impairs social or occupational functioning and frequently requires psychiatric treatment. These disorders are classified in the current Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) (3) as adjustment disorders with depressed mood, anxiety, or mixed anxiety and depressed mood, depending on the predominant manifestation. For these patients, mental health professionals working in oncology use short-term supportive psychotherapy, which offers emotional support, provides information to help the patient adapt to the crisis, emphasizes past strengths, and supports previously successful ways of coping. Anxiolytic or antidepressant drugs are prescribed as indicated and as symptoms improve, medication can be reduced and discontinued. Having the patient talk with another patient who has been through the same treatment is often a helpful adjunct.
Prevalence of Psychiatric Disorders in Patients with Cancer
There are many myths about the psychological problems of patients with life-threatening illness. The assumptions may range from “all patients are in distress and require psychiatric treatment” to “distress is part of the cancer experience and people cope in their own way over time.” One of the first efforts in the field of psycho-oncology was to obtain objective data on the type and frequency of psychological problems in patients with cancer.
Using criteria from the Diagnostic and Statistical Manual of Mental Disorders Third Edition (DSM-III) (4) classification of psychiatric disorders, the Psychosocial Collaborative Oncology Group (PSYCOG) determined the psychiatric disorders in 215 randomly selected hospitalized and ambulatory adult patients with cancer in three cancer centers (5). Although slightly over half (53%) the patients evaluated were adjusting normally to stress, the remainder (47%) had clinically apparent psychiatric disorders. Of the 47% with psychiatric disorders, over two thirds (68%) had reactive or situational anxiety and depression (adjustment disorders with depressed or anxious mood), 13% had a major depression, 8% had an organic mental disorder, 7% had a personality disorder, and 4% had a preexisting anxiety disorder. The authors concluded that nearly 90% of the psychiatric disorders observed were reactions to, or manifestations of, disease or treatment.
Interestingly 39% of those who received a psychiatric diagnosis were experiencing significant pain. Although in contrast, only 19% of patients who did not receive a psychiatric diagnosis had significant pain. The psychiatric diagnosis of the patients with pain was predominately adjustment disorder with depressed or mixed mood (69%); however, it is of note that 15% of patients with significant pain had symptoms of major depression. In a study of cancer pain syndromes, unmanaged pain emerged as a causal factor in patient’s reports of increased anxiety (6).
Both data and clinical observation suggest that the psychiatric symptoms of patients who are in pain (i.e., acute anxiety, depression with despair, agitation, irritability, uncooperative behavior, anger, and inability to sleep may occur) must initially be considered a consequence of uncontrolled pain symptoms. Feelings of hopelessness, helplessness, and occasionally suicidal ideation occur when the patient believes that pain represents disease progression. These symptoms are not labeled as a psychiatric disorder unless they persist after pain is adequately controlled. Clinicians should manage pain (7) and then reassess the patient’s mental state after pain is controlled, to determine whether the patient has a psychiatric disorder.
Impact of Depression and Anxiety on the Management of Patients with Cancer
The timely diagnosis and effective management of depression and anxiety in patients with cancer contribute not only to an improvement in quality of life but also enhanced patient involvement in treatment. A meta-analysis of the effects of depression and anxiety on compliance with medical treatment suggests that patients who are depressed are three times more likely to be noncompliant than patients who are not depressed (8). Additionally, depression may impair patients’ capacity to understand and process information about their prognosis.
Screening for Psychological Distress in Patients with Cancer
The presence of psychological distress can have a significant impact on patients’ lives. However despite this understanding, in the context of a busy oncology clinic, the focus on psychological symptoms is not paramount. Coupled with clinic time pressure is many patients’ concern that alerting their health care providers to their psychological distress may divert their physicians from pursuing the most aggressive cancer regimen. To address this issue, brief pencil and paper screening measures or a visual analog scale measuring psychological distress can rapidly identify patients whose levels of distress warrant further evaluation (9). Teaching oncology staff members to use brief, semi-structured interviews can improve their recognition of anxiety and depressive symptoms.
Prevalence of Depression in Patients with Cancer
In Massie’s review of over 150 studies, the prevalence of major depression in patients with cancer ranged from 0% to 38% and the prevalence of depression spectrum syndromes ranged from 0% to 58% (10). Most of this variance can be attributed to the lack of standardization of methodology and diagnostic criteria. For example, in a study of 152 patients with cancer, Kathol et al. found a 13% difference (25% vs. 38%) in the prevalence of depression depending on the diagnostic system used (11).
The clinical rule of thumb is that 25% of patients with cancer are likely depressed enough at some point in the course of disease to warrant evaluation and treatment. Advanced disease has been correlated with a higher prevalence of depression in several studies. The reported prevalence of depression in patients with advanced cancer has been found to be as high as 26% (10, 12). Greater physical disability is associated with a higher prevalence of depression.
Diagnosis of Depression in Patients with Cancer
The diagnosis of depression in physically healthy people depends heavily on the presence of somatic symptoms, including anorexia, fatigue, insomnia, and weight loss; however, these indicators are of less value as diagnostic criteria for depression in patients with cancer, as they are common to both cancer and depression. In patients with cancer, the diagnosis of depression must depend on psychological (i.e., dysphoric mood, feelings of helplessness and hopelessness, loss of self-esteem, feelings of worthlessness or guilt, anhedonia, and thoughts of death or suicide) not somatic symptoms. Table 40.1 outlines the differential diagnosis of depression.
Table 40.1 Differential Diagnosis of Depression | ||||||||||||
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Mood Disorder Due to Cancer, Other Medical Conditions, or Substances
When evaluating patients who are depressed, it is imperative to determine whether organic factors underlie the depressive syndrome. A depressive syndrome caused by the direct physiologic effects of cancer is called mood disorder due to cancer in the current DSM-IV nosology. The key feature of this disorder is a prominent and persistent depressed mood that resembles a major depression. The presence of encephalopathy precludes the diagnosis of mood disorder due to cancer unless depression had been diagnosed before confusional symptoms developed. The patient with a delirium due to cancer may have cognitive deficits, such as disorientation, poor memory or decreased concentration, fluctuating level of consciousness, and altered perceptions, including hallucinations and delusions. Tumor involvement of the central nervous system, metabolic disturbances (i.e., hypothyroidism, hyperparathyroidism, adrenal insufficiency, folate and B12 deficiencies), and the presumed organic processes associated with carcinoma of the pancreas may be contributing factors to the mood disorder.
Table 40.2 Drugs Associated With Depressive Symptoms | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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DSM-IV defines disturbances in mood due to the direct physiologic effects of a substance (i.e., a drug of abuse or a medication) as a substance-induced mood disorder. This diagnosis would be appropriate when depression is related to drug therapies (Table 40.2), including anticancer drugs (Table 40.3). There are several reports of exogenously administered cytokines, such as interferon-α and interleukin-2 causing depression. These cytokine therapies have been shown to be associated with significant depressive symptoms in 30–50% of patients (13).
The evaluation of every patient who is depressed and has cancer should include a consideration of medical, endocrinologic, and neurologic problems in addition to screening for depressive symptoms. Many clinicians prefer to use an easily reproducible instrument [e.g., the Mini-Mental State Examination (MMSE)] (14) to document elements of the patient’s mental status at the time of the initial evaluation and subsequent evaluations. All such brief instruments have limitations because they assess only selected aspects of cognition. The MMSE can easily and quickly be administered at the bedside and detects impairments in cognition (e.g., orientation, memory, concentration, language, and comprehension). It provides a numerical score out of 30, while accounting for educational level. A change in cognition, especially if acute, should raise suspicion of a nonpsychiatric etiology of concurrent depressive symptoms.
If the depressive disorder is believed to be caused by a medical condition or by a drug, the clinician should first attempt to treat the condition or change the drug. Often, antidepressants are started concurrently in an effort to alleviate symptoms or because the clinician anticipates that the depression that complicates the underlying disorder will not be relieved by addressing the medical condition alone. Only when the primary cause of the depression cannot be corrected (e.g., the chemotherapeutic agent must be continued), should the antidepressant therapy be initiated.
Depression with Psychotic Features
Although rare, depression accompanied by delusions, hallucinations, or grossly disorganized behavior is sometimes
encountered in patients who are medically ill. In this population, the presence of depressive symptoms (e.g., flat affect, lack of interest in daily activities) coupled with psychotic symptoms more often reflect a delirium, and before the diagnosis of depression with psychotic features is made, the presence of the underlying organic causes of these mental status changes should be explored. When psychotic features are present, an antipsychotic and an antidepressant are usually started concurrently. High-potency typical antipsychotics (e.g., haloperidol) and novel antipsychotics (e.g., olanzapine and risperidone) are usually preferred to treat all forms of psychosis, including those associated with delirium and dementia. High-potency typical neuroleptics and risperidone have the lowest rate of seizures (15).
encountered in patients who are medically ill. In this population, the presence of depressive symptoms (e.g., flat affect, lack of interest in daily activities) coupled with psychotic symptoms more often reflect a delirium, and before the diagnosis of depression with psychotic features is made, the presence of the underlying organic causes of these mental status changes should be explored. When psychotic features are present, an antipsychotic and an antidepressant are usually started concurrently. High-potency typical antipsychotics (e.g., haloperidol) and novel antipsychotics (e.g., olanzapine and risperidone) are usually preferred to treat all forms of psychosis, including those associated with delirium and dementia. High-potency typical neuroleptics and risperidone have the lowest rate of seizures (15).
Table 40.3 Anticancer Drugs Associated With Depression | ||||||||||
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Depression in the Elderly
Older individuals are at increased risk for depression and suicidal acts, whether physically healthy or not. In addition to the loss of good health, the elderly patient with cancer often has sustained other losses, including physical ability (e.g., vision and hearing loss) and financial stability. Grief after the death of a spouse or friends may be unresolved, and self-esteem may be damaged through retirement or changed social standing. Although the clinical presentation of depression can be similar to that described for younger adult patients, other presentations are more typical of this phase of life. For example, the chief complaint may be cognitive, such as poor memory or concentration. By taking a thorough history and by interviewing relatives or friends to document the patient’s history, the clinician learns that depressive features may antedate the cognitive complaints. When asked specific questions, the patient often says “I don’t know” instead of attempting to answer. Objective testing (e.g., with the MMSE) often reveals better results than those expected on the basis of subjective complaints. This constellation is typical of the clinical syndrome depressive pseudodementia and often responds well to treatment with antidepressants.
Suicide
Suicidal ideation requires careful assessment to determine whether the patient has a depressive illness or is expressing a wish to have ultimate control over intolerable symptoms. Thoughtful clinical judgment is required to make this differentiation, especially in the patient with advanced disease. Factors that place a patient with cancer at risk for suicide (Table 40.4) include poor prognosis and advanced illness, depression and hopelessness, uncontrolled pain, delirium, history of poor impulse control or psychiatric illness, previous suicide attempts or family history of suicide, history of recent death of friends or spouse, current or previous alcohol or substance abuse, physical and emotional exhaustion, and social isolation. Other risk factors include male gender; advanced age (sixth and seventh decades), and the presence of fatigue.
Although few patients with cancer commit suicide, they may be at somewhat greater risk than the general population (16). Factors such as poor prognosis, delirium, uncontrolled pain, depression, and hopelessness often occur in a patient with advanced disease, increasing the risk of suicide. Hopelessness is an even stronger predictive factor than depression itself (17). Studies exploring the desire for early deaths have found that 1.4–17% of terminally ill patients with cancer who wish to have their lives end naturally or by suicide or euthanasia. Figures range depending on the assessment tools used and populations studied (18).
Table 40.4 Suicide Risk Factors in Patients With Cancer | ||||||||||||||||||||||
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The management of the patient with cancer and suicidal tendencies includes maintaining a supportive therapeutic relationship; conveying the attitude that much can be done to improve the quality, if not the quantity, of life even if the prognosis is poor; and actively eliciting and treating specific symptoms (e.g., pain, nausea, insomnia, anxiety, fatigue, and depression). The most useful psychotherapeutic modalities are based on a crisis intervention model using cognitive techniques (e.g., giving back a sense of control by helping the patient to focus on that which can still be controlled) and supportive methods, sometimes involving family and friends. One should keep in mind that the partner and other family members are also at increased risk for suicide and that they also often require evaluation and support.
When considering the need to hospitalize a patient with suicidal tendencies, evaluation of the risk factors (Table 40.4), including the presence of a plan and its lethality, and associated intent, ensues. If the patient with suicidal tendencies does not have any physiologic factors contributing to their psychiatric presentation, admitting the patient to a psychiatric unit may be indicated. However, during the palliative phase, when patients are too ill to be psychiatrically hospitalized, they may be admitted to oncology wards, where a 24-hour companion can be provided. Companions can provide constant observation, monitor the suicidal risk, and reassure the patient. Need for observation is evaluated daily; companions are discontinued when the patient is no longer suicidal and is judged to be in control and able to act rationally. Similarly, companions or nurses can be provided in hospice settings as well as in the home to ensure patient safety.
Treatment of Depression
Before planning an intervention, the patient should be evaluated for a history of depressive episodes and substance abuse; family psychiatric history, including depression and suicide; concurrent life stresses; losses secondary to cancer
(e.g., financial, social, and occupational) and the availability of social support. An assessment of the patient’s personal experience with cancer deaths, of the meaning of illness, and of the patient’s understanding of the medical situation (including prognosis) is essential. Patients with cancer who are depressed are usually treated with a combination of supportive psychotherapy and antidepressants; electroconvulsive therapy (ECT) is used less often.
(e.g., financial, social, and occupational) and the availability of social support. An assessment of the patient’s personal experience with cancer deaths, of the meaning of illness, and of the patient’s understanding of the medical situation (including prognosis) is essential. Patients with cancer who are depressed are usually treated with a combination of supportive psychotherapy and antidepressants; electroconvulsive therapy (ECT) is used less often.
Psychological Treatment
Evidence from meta-analyses has shown that psychologic treatments effectively treat anxiety and depression in patients with cancer (19, 20, 21). The goals of psychotherapy are to reduce emotional distress and to improve morale, coping ability, self-esteem, sense of control, and resolve problems. Patients with cancer are often referred for, or request for, psychiatric consultation at times of crisis in illness—at the time of initial diagnosis or recurrence, at the beginning of any new treatment, when standard or experimental treatments fail, or when patients perceive themselves as dying. The referral is often an emergency and, because of the acute crisis, the patient often readily accepts an intervention.
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