Diagnosis and Treatment of Depression in Cancer Patients

Diagnosis and Treatment of Depression in Cancer Patients

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.[8]

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.

Defining Depression

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).[16] As shown in Table
, 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.[17] 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.

Assessing Depression in Cancer Patients

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.[18]

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
, the clinician can rapidly (ie, within 5 to 10 minutes) assess
the patient for depression.[19] 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.[19]

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.[23]

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?”[24] This
single-item screening tool outperformed questionnaires and other
screening tools for the eventual diagnostic outcome of evaluations.

Differential Diagnosis

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.[25] 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
).[19] 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.[26] 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).[27] Procarbazine (Matulane), ironically a mild
monoamine oxidase inhibitor, also has been reported to cause
depression.[28] 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.[16] 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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