James L. Levenson, MD
Vice-Chairman of the Department of Psychiatry; Professor of Psychiatry, Medicine, and
Surgery; Chairman of Consultation/Liaison Psychiatry at the Virginia Commonwealth University Medical Center.
Disclosure: Dr. Levenson has served as a consultant for Lilly.
This column reviews psychologic factors affecting the
incidence and course of cancer, the most common comorbid psychiatric disorders
(depression, anxiety, and delirium), psychiatric issues in selected specific
cancers, psychiatric aspects of cancer treatments, and psychiatric treatment in
cancer patients. More comprehensive review of these issues is available
PSYCHOLOGIC FACTORS AFFECTING CANCER RISK AND PROGRESSION
The role of psychologic factors in cancer onset and progression is controversial.2 The large epidemiologic Western Electric study reported that depressive symptoms were associated with twice as high risk of death from cancer 17 years later and with a higher-than-normal incidence of cancer for the first 10 years and at 20-year follow-up.3,4 However, other studies, including recent prospective large cohort studies, found no effect of depression on cancer risk.5 In the year after diagnosis of breast cancer, 50% of women have clinically significant depression, anxiety, or both,6 prompting a large number of studies examining how emotional states affect recurrence or mortality. However, results have been mixed. Depression may affect the course of illness in patients with cancer because it results in poorer pain control, poorer compliance, and less desire for life-sustaining therapy. Research over the past 25 years has both supported and refuted the belief that cancer development or mortality is
influenced by coping, defensive style, or personality traits.2
Bereavement often has been assumed to be a risk factor in cancer onset and progression. A meta-analysis of 46 studies found only a modest association between separation or loss experiences and development of breast cancer.7 Considering retrospective, prospective, clinical, and population-based studies, bereavement has not to date been convincingly shown to influence cancer onset or progression.2 Some early studies linked stressful life events to progression or recurrence of cancer, but later reports have found no effect of stressful life events on relapse or progression.
PSYCHIATRIC DISORDERS IN CANCER PATIENTS
An individual’s psychologic response to cancer is influenced by specific aspects of the cancer. A person’s ability to manage a cancer diagnosis and treatment commonly changes over the course of the illness and depends on medical, psychologic, and social factors. These include the disease itself (ie, site, stage, clinical course, cancer treatments, and their complications); prior personality, coping style, and mental health; stage of life; social support; and cultural and religious background.
Cancer is associated with a higher rate of depression than in the general population comparable to other serious medical illnesses8 and may represent a normal reaction, a psychiatric disorder, or a somatic consequence of cancer or its treatment. Cancer types particularly associated with depression include oropharyngeal, pancreatic, breast, and lung.
Because cancer may itself cause anorexia, weight loss, fatigue, and other vegetative symptoms, diagnosis of clinical depression relies more heavily on psychologic symptoms like social withdrawal, anhedonia, dysphoric mood, feelings of worthlessness or guilt, poor self-esteem, and suicidal thoughts. Thus, there is a risk both of underdiagnosis of depression in cancer patients (misattributing depressive symptoms to the cancer and a normal reaction) and overdiagnosis (misattributing cancer-caused symptoms and normal emotional upset to clinical depression). An increased risk of suicide in cancer patients is associated with advanced stage of disease, poor prognosis, delirium, inadequately controlled pain, depression, history of psychiatric illness, substance abuse, previous suicide attempts, and social isolation.1 Passive suicidal thoughts are far more common than true suicidality in cancer patients, yet may be expressed in some patients’ noncompliance with or refusal of treatment.
Anxiety leads some patients to deny or ignore cancer symptoms and delay seeking medical attention.
Symptoms of anxiety are common after initial diagnosis of cancer, in making treatment decisions, and when worrying about recurrence or progression, but the rate of full anxiety disorders may not be higher than in the general population.9 Specific anxiety syndromes can interfere with treatment. Patients with claustrophobia have difficulty tolerating magnetic resonance imaging scans, radiation therapy, or isolation because of neutropenia. Needle phobia may interfere with chemotherapy, and fear of anesthesia gets in the way of
surgery. Radiation phobia makes some patients reluctant to accept radiation treatment.1 Chemotherapy can cause conditioned responses of nausea, vomiting, and intense anticipatory anxiety, but this has become less common with improved antiemetic drugs. The traumatic experiences of cancer and its treatment may give rise to posttraumatic stress disorder. The differential diagnosis of acute anxiety in cancer patients includes antiemetic-induced akathisia, undertreated pain, pulmonary emboli, and delirium.
Psychosis and Delirium
Mania in cancer patients is usually due to preexisting bipolar disorder or high-dose corticosteroids,
and only rarely due to other drugs (eg, interferon) or brain tumors. Delirium is common in cancer patients as a result of the disease and its treatment, and particularly in the terminal stage of illness. Specific causes include brain tumors (metastatic or primary),antineoplastic drugs (eg, cytarabine, methotrexate, ifosfamide, asparaginase, procarbazine, fluorouracil), immunotherapeutic agents (eg, interferon and interleukins), infection (especially in immunosuppressed patients), some antimicrobials (eg, amphotericin), opioids, hypercalcemia, and the rare paraneoplastic syndrome, limbic encephalopathy.
PSYCHIATRIC ASPECTS OF SPECIFIC CANCERS
Psychologic responses to breast cancer and its treatment vary with women’s age, personality, and family
and relationship circumstances because of the varying relevance of fertility, body image, side effects of treatment (eg, alopecia, premature menopause with hot flashes, irritability, and depression), and genetic testing. Family and relationship issues include marital status; the partner’s role; family history of cancer; sexual, pregnancy, and breast-feeding history; and desire to have (more) children. Genetic testing can now identify women at risk for the hereditary breast cancer/ovarian cancer syndrome. Women at high risk are confronted with decisions about prophylactic mastectomy or prophylactic oophorectomy, and how and when to inform their mothers, sisters, daughters, and granddaughters. Some women at high risk request prophylactic mastectomy without having had genetic testing, in which case, psychiatric evaluation should be considered.
Almost 90% of lung cancers are attributable to cigarette smoking. While many smokers with cancer experience guilt, many continue to smoke. Smokers are at higher risk for depression. Some patients and their physicians take a fatalistic attitude and conclude there is no point in trying to stop smoking once the diagnosis of lung cancer has been made. However, continued smoking is associated with decreased survival after diagnosis of lung cancer, so early antismoking intervention is warranted. In terminal lung cancer, if the patient derives pleasure from smoking, there is nothing to be gained from cessation efforts.
Cognitive dysfunction may be the result of brain metastases (very common in lung cancer), leukoencephalopathy caused by chemotherapy and cranial radiation, paraneoplastic syndromes with small-cell lung cancer (eg, hyperadrenalism, hyponatremia, limbic encephalitis), and pulmonary emboli.
Head and Neck Cancers
Head and neck cancers are most frequent in patients with a history of alcohol abuse and smoking. Treatment often causes facial deformity, loss of speech, problems with eating because of mucositis, pain, dysphagia, and dry mouth. Feeding tubes and tracheotomies are often necessary.
Patients’ psychologic reactions to colorectal cancer are mainly determined by the extent of surgery, the presence of a stoma and ostomy, and the prognosis. Concerns about body image, leakage, odor, and sexual functioning can lead to social withdrawal. For those with ostomies, self-help groups can provide support, education, and coping skills for patients and their families.
Depression has long been thought to be a common harbinger of pancreatic cancer, before physical signs appear. A recent epidemiologic study found that depression preceded pancreatic cancer more often than it did before other gastrointestinal malignancies (odds ratio 4.6).10 In a depressed patient, clues to the diagnosis of pancreatic cancer include abdominal pain and weight loss out of proportion to the degree of psychologic symptoms. However, the symptoms of pancreatic cancer are typically vague and nonspecific.1
The serum prostate specific antigen test has facilitated early detection of prostate cancer but considerable anxiety can follow because of treatment uncertainties. One uncertainty is when to actively treat because of the difficulty distinguishing between slow-growing prostate tumors with low risk for morbidity and mortality versus more aggressively malignant tumors. In addition, the choice between active treatments is difficult due to uncertainty of which treatment (surgery versus radiation) has the best benefit-to-burden ratio. The choice is often based on the potential consequences of urinary incontinence and impotence. Androgen deprivation therapy via orchiectomy or gonadotropin-releasing hormone agonists may cause hot flashes, diminished libido, fatigue, weakness, and muscle atrophy, and is associated with poorer quality of life.11
PSYCHIATRIC ASPECTS OF CANCER TREATMENTS
The neuropsychiatric side effects of common chemotherapeutic agents are described in detail elsewhere.1 The effects of chemotherapy on cognition have not yet been clearly elucidated.12 There are few clinically significant interactions between cancer drugs and most psychotropics, with the exception of procarbazine, which is a weak monoamine oxidase inhibitor.
Brain irradiation causes more profound fatigue than radiation treatment of other sites. Late sequelae of brain radiation may include radiation necrosis in focal areas or leukoencephalopathy.1
Bone Marrow Transplantation
Patients undergoing bone marrow transplantation (BMT) have been reported to experience high levels of depressive and anxiety symptoms.1 The greatest emotional distress may occur after hospital admission and prior to bone marrow infusion. However, during high-dose chemotherapy and irradiation, while patients are limited in contact with their family (and frequently in isolation) and experience profound nausea, vomiting, and fatigue, psychiatric disorders remain common, especially adjustment disorder with anxiety and depression. As many as 50% of BMT patients experience delirium during the posttransplantation period,13 with severe graft-versus-host disease as one possible cause. While chronic anxiety and depression are the most common psychiatric sequelae, long-term survivors of BMT show no difference in psychologic and social functioning than those who received standard chemotherapy. However, mild-to-moderate cognitive impairment is common.1
PSYCHIATRIC TREATMENT IN CANCER
Psychotherapy can help patients cope with the diagnosis and treatment of cancer, relieving psychic suffering while supporting patients’ morale, search for meaning, and desire for dignity at the end of life.14,15 Most studies of group therapy in cancer patients have shown improvement in mood, pain, and quality of life.16,17 Relaxation training and cognitive- behavioral therapy also have reduced anxiety and depression in cancer patients.1 Spiegel and colleagues17 performed a small randomized controlled trial of supportive group therapy with training in self-hypnosis for pain control in women with metastatic breast cancer. The subjects in the psychotherapy treatment group had less mood disturbance, fewer phobic responses, and less pain, but were also noted to have increased survival compared with the control group (34.8 versus 18.9 months). The possibility that a psychologic intervention might improve longevity in metastatic breast cancer patients was exciting and supported by some other studies.18 However, it was not supported by the definitive replication study16 and other studies. Thus, the evidence is that psychotherapy in cancer patients results in improvement in indices of quality of life such as mood, energy, and pain control. Patients can be told that group therapy contributes to living better, though not necessarily longer.
The selective serotonin reuptake inhibitors (SSRIs) may cause nausea and weight loss in some cancer patients, particularly those with cancer-related anorexia-cachexia. Mirtazapine and trazodone may be advantageous in such patients. Fluoxetine’s long half-life makes it useful for patients intermittently unable to tolerate oral intake (eg, somatitis from chemotherapy). The SSRIs and serotonin norepinephrine reuptake inhibitors (SNRIs) reduce hot flashes in abrupt menopause caused by chemotherapy or oophorectomy, and may help with hot flashes caused by treatment in men with prostate cancer. In addition to their psychiatric indications, tricyclic antidepressants and SNRIs are used to treat neuropathic pain syndromes caused by malignancy or its treatment. In addition to their antianxiety effects, benzodiazepines (most often lorazepam) are frequently prescribed to augment antiemetic drugs during chemotherapy. Low doses of neuroleptics are used in the treatment of delirium in cancer patients as in other patients with delirium. Psychostimulants are used for the treatment of depression in terminally ill cancer patients because there is no delay in onset of therapeutic effects, and more generally may palliate fatigue and augment opioid analgesia while counteracting sedation. PP
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