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 and 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 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 (Matulane), L-asparaginase
(Elspar), interferon, vinblastine, vincristine, tamoxifen, and 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.