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FOCUS, VOL. 7, No. 3

CLINICAL SYNTHESIS | June 01, 2009

Psycho-Oncology: A Review for the General Psychiatrist

Fremonta Meyer, M.D.; Matthew Ehrlich, M.D.; John Peteet, M.D.

FOCUS 2009;7:317-331.

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CME Disclosure

Fremonta Meyer, M.D., Department of Psychosocial Oncology and Palliative Care, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Harvard Medical School, Boston, MA

No relevant financial relationships to disclose.

Matthew Ehrlich, M.D., Cambridge Health Alliance, Harvard Medical School, Boston, MA

No relevant financial relationships to disclose.

John Peteet, M.D., Dana-Farber Cancer Institute and Brigham and Women's Hospital, Harvard Medical School, Boston MA

No relevant financial relationships to disclose.

Address correspondence to Fremonta Meyer, M.D., 44 Binney Street SW411, Dana-Farber Cancer Institute, Boston, MA 02115; e-mail: fremonta_meyer@DFCI.HARVARD.EDU

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Abstract

This article provides an overview of psycho-oncology, including epidemiology of common psychiatric conditions in cancer, effects of cancer and chemotherapy on the brain, and effects of coping styles and other psychosocial factors on cancer treatment. It describes the assessment, differential diagnosis, and treatment of adjustment disorders, anxiety, depression, delirium, chemotherapy- and radiotherapy-induced cognitive dysfunction, character disorders, substance disorders, and major mental illness in oncology patients. Survivorship and bereavement are addressed, as are future directions for this growing field.

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DEFINITION

Psycho-oncology is a multidisciplinary subspecialty of oncology concerned with the emotional responses of patients, their families, and staff at all stages of disease. It also examines the psychological, social, and behavioral variables that influence cancer risk, prevention, and survival (1).

The formal history of psycho-oncology began in the mid-1970s in the United States. Only at this juncture had the stigma of cancer diminished to the point that most patients were told their diagnosis, allowing the study of their emotional responses. Social workers and nurses initially addressed the psychosocial problems of patients with cancer and their families, with early research in the field conducted mainly by consultation liaison psychiatrists. Subsequent investigators included health psychologists (studying theoretic models of coping and cognitive behavior interventions), behavioral psychologists (studying lifestyle changes such as smoking cessation and dietary modification to reduce cancer risk), and nursing researchers (studying symptom management and control, pain management, and psychological support). The field is notably multidisciplinary (2), although our review will highlight aspects of particular relevance to the practicing psychiatrist.

EPIDEMIOLOGY AND NATURAL HISTORY

Depression, anxiety

As one might expect with any severe illness, cancer tends to increase the prevalence of certain psychiatric symptoms and syndromes above baseline population levels. By far the most prevalent conditions are those that are also prevalent among nononcologic populations: depression and anxiety disorders. However, clinicians appear to underrecognize the severity of psychiatric illness in this population. One large study of depression found a concordance of only 13% between oncologist and patient scales in those with severe symptoms; nurses had no greater concordance (3, 4).

In advanced cancer, prevalence estimates of major mental illness vary widely, depending on the criteria used; use of small samples or non-DSM instruments can result in rates up to five times those found using more rigorous criteria. One study with strict criteria found that approximately 12% of patients met the criteria for at least one major mental illness. Rates of depression were 6.8%, panic disorder 4.8%, and generalized anxiety disorder 3.2% (5). Caregivers were equally affected; panic disorder was the most common (8%), followed by major depressive disorder (4.5%), posttraumatic stress disorder (PTSD) (4%) and generalized anxiety disorder (3.5%). If adjustment disorders are included, the prevalence of mental illness may be as high as 50% of all patients with advanced cancer, with high levels of comorbidity (6 —8). Subsyndromal disorders are quite prevalent, with high rates of significant anxiety symptoms, especially posttraumatic ones (9).

The prevalence of depression in cancer has possibly decreased in recent years, perhaps due to changes in outcomes, stigma, palliative care, and screening with treatment (10). The validity and prevalence of relevant constructs such as demoralization (11) and conservation-withdrawal (12), which may be mistaken for or overlap with depression, are contested.

Progressive disease may not cause substantially greater rates of illness than less symptomatic disease (7, 13). However, this finding has been disputed by other researchers who found that metastasis increases risk of depression (14, 15). Its effect on severity of symptoms is unclear: nearing death, existential distress increases with increased physical symptom burden, not with closeness to death (16). In terminal phases, some authors report that rates of depressive disorders may actually decrease and anxiety disorders may increase by only 1%—2% absolute prevalence (approximately a 20% relative increase) (7). Patients who are younger or have less social support have a greater risk (8).

Delirium

Delirium is a frequent complication in patients with advanced cancer, occurring in 28%—44% of hospital admissions and in 90% of patients before death (17). In the palliative care setting, hypoactive delirium is most prevalent, constituting up to 86% of delirium, and confers a worse prognosis (18). Hyperactive delirium occurs in 13%—46% of palliative care patients (19). A reversible etiology is discovered in less than 50% of patients with advanced cancer with delirium. The 1-month mortality rate may be up to 83% in this patient population (20).

Fatigue

More than 80% of outpatients undergoing chemotherapy or radiation treatment experience fatigue, which is also associated with stem cell or bone marrow transplantation and hormonal therapy. In up to 33% of patients, fatigue can persist for months or years after the conclusion of cancer treatment (21).

Bipolar disorder

Bipolar disorder has a prevalence of 0.4%—1.6% in the general population, which should be similar for cancer patients. Antidepressants, corticosteroids, stimulants, and interferon can all induce or exacerbate mania in patients with bipolar disorder (7).

Character disorders

Narcissistic, histrionic, and borderline personality disorders tend to cause the most problems in medical settings. The prevalence rate in patients with cancer is about the same as that in the general population, i.e., 2%—3% each for borderline and histrionic personality disorders and 1% for narcissistic personality disorder (6).

Schizophrenia

Prevalence rates of schizophrenia are 0.5%—1.5% worldwide. Despite some evidence that patients with schizophrenia have an increased overall cancer risk (16, 22), these rates should be similar in cancer patients. Any increased risk is probably attributable to specific lifestyle factors, particularly tobacco smoking and alcohol consumption.

Substance use disorders

Substance abuse diagnoses such as tobacco and alcohol dependence substantially increase the risk of lung and head/neck cancer. Prevalence rates of alcohol dependence among patients with cancer with pain may be elevated above baseline, perhaps as high as 28% (23). Alcoholism is associated with increased need for opioids (23, 24) and worse outcome in some cancers (25). The highest rates of alcohol dependence (33.6% in one study) are found in head/neck cancers (26).

Suicidality

Thoughts of suicide may be present in up to 17% of patients with cancer (27). Hopelessness is at least as strong a contributor as depression to suicidal ideation (28). Rasic et al. (29) found that among those aged 54 and younger, there was no increase in suicidal ideation with cancer, but for those older than 54, there was an odds ratio of 5.07 (which disappeared with adjustment for sociodemographic factors and mental disorders). The differential diagnosis of suicidal ideation in this population must always include encephalopathic conditions; the presence of hallucinations or delusions is a risk factor for suicide attempts (30).

Suicidality differs from a desire for hastened death. Ten to 30% of terminally ill persons with cancer report a desire for hastened death. This desire has two strong independent contributors, depression and hopelessness (31). An unknown but substantial frequency of patients with cancer demonstrate contingent suicidality, a situation in which patients link their suicidal intent to a future time point or particular life circumstance (32) (for example, severe pain or dyspnea as natural death approaches). Early reports suggest that a minority of family members of cancer patients who struggle with severe anticipatory grief are also at risk for contingent suicide upon the death of their loved one (33). Cancer is the only nonpsychiatric condition independently associated with completed suicide (odds ratio 2.3), and metastatic disease further raises the risk (34). Adjusted rates of suicide are 31.4/100,000 person-years among those with cancer, compared with 16.7 in the general population (35). Nonetheless, completed suicide is rare: only 0.03% of deaths in patients receiving palliative care and 0.2% of all deaths in patients with cancer are due to suicide (36).

Risk factors for suicide among those with cancer include male sex, white race, and unmarried status; lung cancer is associated with the highest rates, followed by stomach and oropharyngeal/laryngeal cancers (35). The risk is highest in the first 5 years after diagnosis, but remains elevated for at least 15 years (35). A mood disorder is present in 80% of completed suicides among those with cancer (37).

BIOPSYCHOSOCIAL UNDERPINNINGS

Biological effect of cancer and cancer treatments on psychiatric syndromes

Brain metastases.

During the course of their illness, 8%—10% of cancer patients will develop brain metastases. The frequency appears to be rising because of improved imaging modalities as well as longer survival after a cancer diagnosis due to improved treatment of systemic disease. The majority of brain metastases arise from one of three primary tumors: lung cancer (45%—50%), breast cancer (15%—25%), and melanoma (5%—20%). Of patients with brain metastases, 65% present with cognitive impairment. Other common presenting symptoms include headaches, seizures, neurologic deficits (38), and anxiety/depression (39).

Leptomeningeal carcinomatosis.

This complication is seen in 5%—8% of cancer patients, with the highest frequency in breast cancer, lung cancer, melanoma, leukemia, and lymphoma. It is usually a late occurrence in cancer and associated with active systemic disease. The clinical manifestations are protean, including headaches, nausea/vomiting, cranial nerve palsies, and spinal cord symptoms. Relevant to psychiatrists, somnolence and confusion may be the only presenting symptoms (40).

Chemotherapy.

Delirium may occasionally be observed as an adverse effect of several cytotoxic chemotherapies (41) (Table 1). Certain biological response modifiers can also cause acute neuropsychiatric toxicities (Table 2).

Table 1. Neuropsychiatric Toxicities of Chemotherapeutic Agents

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Table 2. Neuropsychiatric Toxicities of Biological Response Modifiers

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During and after chemotherapy, some patients experience more insidious difficulties with memory, attention, and executive function, a phenomenon known commonly as "chemo brain." Cognitive dysfunction has been reported in as many as 50% of women undergoing chemotherapy for breast cancer (42) and has also been observed in patients after stem cell transplantation (43) and after chemotherapy for other solid tumors (44). In a minority of patients, chemo brain is still perceptible and psychologically distressing 10 years after treatment (45).

Radiation therapy

Whole brain radiotherapy (WBRT) for metastatic disease offers tumor shrinkage and palliation, which has been associated in some studies with better preservation of neurocognitive functioning (46). However, WBRT itself is associated with cognitive impairment, specifically preferential adverse effects on hippocampal functions of learning, memory, and spatial information processing (47). Certain quality-of-life parameters, specifically fatigue, drowsiness, and appetite, may worsen after WBRT (39).

Paraneoplastic limbic encephalitis.

This rare autoimmune neuropsychiatric complication may either herald a malignancy or follow a cancer diagnosis. It presents with subacute memory loss and other limbic symptoms such as depression, seizures, hallucinations, and personality change (48). Typically associated malignancies are small cell lung cancer in approximately 40% of patients and seminoma in approximately 25% of patients, with nearly any other tumor associated at a lower rate (49). Clinical suspicion should prompt a lumbar puncture to rule out herpes simplex viral infection or leptomeningeal cancer spread and brain magnetic resonance imaging to rule out metastatic disease. If these studies are unrevealing, antineuronal antibodies (anti-Hu, anti-Ma, anti-Ta, and others) should be used as these are required for definitive diagnosis.

Effect of coping style/psychosocial factors on cancer

Mortality and survival.

How important are psychosocial factors to the mortality and survival time outcomes of cancer treatment? The evidence is strongest for ethnosocioeconomic factors, which affect treatment and outcome in many areas of health. African Americans have a lower 5-year survival rate for all cancers than whites (57% versus 68%) (50).

Depression may predict progression and mortality, although this theory is disputed (10, 51, 52). There is evidence that many psychological and social factors that appear to affect outcome are mediated by adherence to treatment (53, 54). For coping style, stress, and social support, constructs that are not widely validated or consistently used, evidence of an independent effect is mixed or inadequate (55, 56). Even for psychosocial interventions evidence of an effect is only weak or inconsistent apart from an effect on adherence (53, 54).

However, psychosocial interventions can be a key to increased adherence and improved outcomes: "meta-analyses show that adherence reduces the risk of a poor treatment outcome by 26% … and the odds of nonadherence is three times higher if comorbid depression exists." (53) The PROSPECT trial showed that patients with major depression in primary care practices with depression care algorithms were less likely to die from cancer than those in other practices (this algorithm included citalopram with or without interpersonal therapy) (57).

Health-related quality of life at baseline does appear to be of some prognostic value. However, despite the clear effect of many psychosocial interventions on quality of life, they do not appear to affect survival (55, 58).

Other outcomes: distress and quality of life.

The effect on quality of life and other outcomes is more robust. Cancer diagnosis, treatment, and disease progression are potentially severely impairing. According to Block (30), "Psychological distress impairs the patient's capacity for pleasure, meaning, and connection; erodes quality of life; amplifies pain and other symptoms; reduces the patient's ability to do the emotional work of separating and saying good-bye; and causes anguish and worry in family members and friends."

Defense mechanisms.

Less adaptive defense mechanisms such as denial and distortion are frequently brought to the forefront in discussions of cancer, based on the belief that facing death inevitably brings out primitive defenses. This belief has been challenged in recent years, as treatment advances have disentangled a cancer diagnosis from certain death, and the growing hospice and palliative care movement has enabled patients to discuss mortality and the death process openly and with some control.

However, denial is not infrequently present: a review of the literature found denial of diagnosis in 4%—47%, denial of impact in 8%—70%, and denial of affect in 18%—42% of patients with cancer (59). Denial itself is not a necessary precondition for hope, and the will to live is not necessarily reduced by the acknowledgment of mortality. Most patients with metastatic cancer say that they have both hope and the will to live, without denial or minimization (36, 60).

Idealization and devaluation of treatment team members is common; often idealized is the surgeon or oncologist in whose hands the patient imagines his or her life. Isolation of affect and intellectualization are commonly transitional defenses, especially in patients who have been wary of affect at baseline or who fear that their emotions might add to the burden on their loved ones. A surprising number of cancer patients and survivors prioritize altruism and humor, mature defenses that may assume greater prominence in their lives than before diagnosis.

Avery Weisman discussed two major features of patients' experience of cancer: coping and vulnerability. In his study, so-called "good copers" are self-fulfilling, in the sense that their key characteristic is the persistence of belief that they can cope; they are practical and address issues directly. "Bad copers" are characterized by self-pity and pessimism (61, 62). Vulnerability is divided into dysphoric and dispositional types, the former being based on patient reports of current experience and symptoms (resembling an axis I depression). Dispositional vulnerability instead reflects underlying character dynamics, including one's sense of the plight of being a cancer patient, and includes subdispositions of annihilation, alienation, endangerment, infringement, and denial (63).

Phases of illness.

Weisman (1979) also proposed a model of coping with cancer, taking into account the existential vulnerabilities associated with a diagnosis: annihilation, alienation, endangerment, and denial. These correspond, respectively, with emotional responses of anxiety, depression, anger, and inappropriate (elevated or dissociated) affect. He found four phases:

ASSESSMENT AND DIFFERENTIAL DIAGNOSIS

General issues

Several aspects of the initial psycho-oncology evaluation distinguish it from an intake assessment in general adult psychiatry. Asking about patients' religious or spiritual preferences may tap into crucial internal strengths and sources of external support or reveal existential distress (64). Referral to a chaplain may be indicated (65). A longitudinal history of the individual's coping style is useful, particularly as it relates to prior medical illnesses. Much information can be gleaned from the patient's account of events just before the cancer, including themes such as anger over a missed or delayed diagnosis or unresolved grief over recent losses. Asking about family members, friends, or acquaintances with cancer may expose the patient's preconceived ideas or fears about the illness. Because cancer often involves a loss of physical and sexual vitality, patients may find themselves sensitized to previously buried memories of prior deaths or losses. It is also essential to inquire into how cancer has affected marital/romantic relationships and dependent children (66). Finally, including in the outpatient setting, a comprehensive Mini-Mental State Examination (MMSE) and some measure of executive function (e.g., the Clock Drawing Test) are useful to obtain at baseline, given the high incidence of cognitive dysfunction seen over time. Neurocognitive decline should prompt consultation with oncologists regarding a CNS workup.

Depression

Diagnosis of depression in oncologic settings is vital, but not straightforward. Several of the diagnostic criteria for major depressive disorder are confounded by symptoms resulting from cancer or its treatment, specifically low energy, poor appetite, and impaired concentration. In addition, several other constructs have been proposed to describe psychological symptoms of low mood, interest, or rumination; some authors differentiate grief, demoralization, hopelessness, or conservation-withdrawal from depressive disorders overall.

Demoralization, in particular, deserves clarification. As Kissane et al. have proposed, it includes the following features, which can be assessed with the Demoralization Scale (11, 68):

In assessing major depression in this population, criteria of particular interest include anhedonia, early morning awakening, disability out of proportion to condition, and somatic preoccupation with intractable symptoms. The six-item Brief Edinburgh Depression Scale, initially developed for post-partum settings, may be useful as a screening tool for oncology practices (67). Even briefer, two questions ("Are you depressed?" and "Have you lost interest in things you usually enjoy?") are reasonably accurate in excluding depression, although they are inadequate for confirming depression (69).

Suicide/requests for hastened death

Suicidal ideation and/or requests for physician-assisted suicide require careful psychiatric evaluation. Contributing psychodynamic factors may include a need for control, ambivalence (i.e., communicating desires to the physician may reflect an underlying wish for rescue), or a split in the experience of the self (in which the medically ill self is experienced as an intrusive entity that needs to be eradicated for the good self to survive). Other possibilities include suicide as a means of revenge against loved ones, atonement for guilt (especially if the cancer was initially attributed to bad deeds and unacceptable emotions), and actualizing a "felt experience" of already being dead (70).

Anxiety

The differential diagnosis of anxiety in patients with cancer is broad and includes biological, psychological, and spiritual factors. Categories of particular importance include DSM-IV anxiety spectrum disorders, other DSM-IV disorders of which anxiety is merely an associated symptom, medical conditions (especially pulmonary), and social/spiritual factors (Table 3).

Table 3. Differential Diagnosis of Anxiety in Persons with Cancer

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