Case 5

55-year-old man with fatigue – Mr. Kish

Author: Klara K. Papp, PhD, Case Western Reserve University School of Medicine

Summary of clinical scenario: Mr. Kish is a 58-year-old male with a past

medical history of obstructive sleep apnea who presents with a 6-week history of
depressed mood, fatigue, poor appetite associated with weight loss, difficulty
concentrating, feelings of guilt and anhedonia without other systemic symptoms in
the setting of his wife's recent diagnosis of metastatic breast cancer. He is
diagnosed with major depression and treatment is initiated. He returns to clinic
with worsening depression and is referred to a mental health specialist.

Final diagnosis: Major Depression

Key Findings from History:

6-week history of depressed mood, fatigue, poor appetite associated with weight
loss, difficulty concentrating, feelings of guilt and anhedonia

Key Findings from PE:

Somewhat psychomotor-slowed with quiet speech and mild motor retardation.
Otherwise normal.

Key Teaching Points

Knowledge:
Fatigue:
Fatigue refers to a sesation of exhaustion during or after usual activities, or a
feeling of inadequate energy to begin these activities. Fatigue should be
distinguished from somnolence, dyspnea and weakness, although these symptoms
often are associated with fatigue.

Alcohol abuse screen:

The CAGE questions are a quick way to screen for problem alcohol drinking. If a
patient responds ”yes“ to 2 or more questions, you should investigate further. The
CAGE questions are:

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 Have you ever tried to Cut down on your drinking?
Have you ever been Annoyed by others commenting on your drinking?
Have you ever felt Guilty about how much you drink?
Have you ever had an Eye opener to prevent symptoms of withdrawal or
reduce a hangover?

The CAGE Questionnaire was reported to have sensitivity of 85% and specificity of
89% for detecting the presence or absence of alcoholism and alcohol abuse in a
sample of 518 patients admitted to the orthopedic and medical services of a
community-based teaching hospital during a 6-month period. Consider carefully
the sample of patients on whom the validity evidence is assessed. For example, in
a predominantly black female population, that sensitivity and specificity data
reported above were consistent, i.e., reported to be 84% and 92%. However,
sensitivities were lower (38%-50%) in predominantly white female populations.

Epidemiology of Major Depression:

Major depression is a very common diagnosis in primary care. In fact, it probably
affects 5-10% of patients in the primary care setting, and in patients with
comorbid conditions such as diabetes, coronary artery disease, HIV, obesity, and
stroke, the rates are even higher. Unfortunately, many people are never diagnosed
and therefore never receive treatment. And for patients with underlying chronic
illnesses such as diabetes and heart disease, untreated depression can be a
barrier to the treatment of their chronic diseases. So it is outstanding that you
have thought of this as a possible reason to explain Mr. Kish's fatigue. You may
have noticed that in our clinic, we follow the USPSTF recommendation to screen
adults annually for depression.

DSM-IV Diagnostic Criteria:

The diagnostic criteria for major depressive episode according to the American
Psychiatric Association's Diagnostic and Statistical Manual 4th Edition (DSM-IV)
are at least five of the following nine symptoms, one being a depressed mood or
loss of interest or pleasure. The symptoms must be present most of the day
nearly every day for a minimum of two consecutive weeks:

1. Depressed mood
2. Loss of intererests/ pleasure
3. Change in sleep
4. Change in appetite or weight
5. Change in psychomotor activity
6. Loss of energy
7. Trouble concentrating
8. Thoughts of worthlessness or guilt
9. Thoughts about death or suicide

Bipolar disorder:
It is important to evaluate for mania in a patient with major depressive episode
because patients with bipolar disorder require different treatment than those with

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 major depressive disorder. You also remember that patients with bipolar disorder
have periods of euphoria, sleeplessness and racing thoughts. Bipolar disorder is
underrecognized in patients who have been diagnosed with depression.
Outpatients being treated for depression in a Family Medicine clinic were
administered a screening questionnaire for bipolar disorder (the Mood Disorder
Questionnaire, or MDQ). Results were positive in 21 percent of patients; two
thirds of the patients who screened positive had never been diagnosed with
bipolar disorder, for more information go to the mood disorder questionnaire.

Patients in whom bipolar disorder is suspected should usually be referred to a

mental health professional. Most important, the antidepressants used to treat
major depression could trigger a manic episode in patients with bipolar disorder.
Severe bipolar episodes can have major ramifications for patients’ jobs, finances
and relationships. The consequences of misdiagnosis can be devastating.

Dysthymia vs Normal Grief vs Major Depression:

Dysthymia requires a two-year history of low-level depressive symptoms. Mr. Kish
was appropriately screened for depression at his last visit with Dr. Anderson and
did not have symptoms at that time. He is unlikely to have dysthymia. The
distinction between major depression and normal reaction to grief or loss can be
difficult. The most common error clinicians make is assuming that "anyone would
feel lousy" given what their patient is dealing with. Studies consistently show that
the majority of people do not respond to severe life stressors with depression and
that when symptoms of depression are present, patients benefit from treatment.

Suicide Risk:
The evaluation of the risk of suicide is very important because it will determine the
type of care needed by the patient after the initial evaluation. This care may
prevent the tragedy of a patient committing suicide and possibly avoid one of the
most traumatic experiences in the professional life of a health professional.
Regarding the rate of suicide, "actuarial analysis reveals that most depressed
patients do not kill themselves. For instance, the 2002 national suicide rate in the
general population was 11 per 100,000. The suicide rate or absolute risk of suicide
for individuals with bipolar or other mood disorders is estimated to be 193 per
100,000."

When seeing patients with depressive symptoms, most primary care physicians do
not consistently inquire about suicidality. Yet worldwide, suicide is the leading
cause of death and potential life-years lost. Studies have shown that "although
many patients are reluctant to seek and actively engage in mental health
treatment, up to 75% of those who complete suicide have seen a primary care
clinician in the previous 30 days."

Access to handguns, chronic health issues, and drug or alcohol abuse are all risk
factors for a completed suicide. Men are more likely than women to be successful
in a suicide attempt. Individuals who are single, divorced, separated or widowed
are also at increased risk for a completed suicide. Some other risk factors include:
age greater than 65, white race or Native American ethnic background,

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 unemployed status, or a family or personal history of suicide. Depressed men who
have higher levels of impulsivity or aggression are also at increased risk of
completed suicide. In one study, protective factors included patients who
expressed more feelings of responsibility toward family, more fear of social
disapproval, more moral objections to suicide, greater survival and coping skills,
and a greater fear of suicide.

Barriers to seeking care for depression

Financial issues affecting access to health professionals and medications.

Misconceptions about psychiatric medications, including side effects,
addiction potential, and others.
Difficulty in accepting depression as a disease rather than as a personal
weakness.
Stigma of mental illness in general.

Some of the barriers are more pronounced depending on the patient's age, sex
and cultural background. It's important to explore the patient's perspective. Mr.
Kish grew up with parents who experienced the deprivations of World War II and
subsequently lived under communism in Central Europe. They generally seek
medical attention when their problems are really bothering them and do not
necessarily trust the advice and remedies that are offered.

Skills:
History-taking:

Elicit the symptoms of major depression.

Determine the presence or absence of underlying dementia, anxiety
disorders, adverse drug effects, and grief in any patient suspected of having
major depression.
Obtain a complete drug history (including illicit drugs).
Identify chronic diseases that are associated with increased risk of major
depression

Physical exam:

Obtain a complete neurologic and mental status exam.

Differential Diagnosis:

thyroid disease
lung cancer
pancreatic cancer
obstructive sleep apnea
major depressive episode

Depression is not a diagnosis of exclusion and can be made based on the history
and physical exam.

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 Laboratory interpretation:

After a clinical diagnosis of Major Depressive Disorder, no further laboratory

studies are required to explain fatigue in a patient with no other medical
problems, symptoms or major risk factors.

When there are possible co-morbidities, patients should have appropriate

screening tests for other illnesses which may cause or contribute to depression.
These include alcohol and substance abuse disorders, thyroid disease, sleep
apnea, adrenal disease, and some cancers.

Older patients could be screened for thyroid disease, but this is not uniformly
recommended. Anemia may have no associated symptoms and is easy to screen
for. A CBC will also evaluate for leukemia, which can cause fatigue without other
symptoms. A drug screen should be considered for most patients with major
depression, and the patient should always be informed that you are ordering the
test. A metabolic panel will quickly and easily reassure you that the patient's renal
function and liver enzymes are normal. These are important when beginning
treatment with antidepressants.

Management:
Given the diagnosis of major depression, it is appropriate to begin an
antidepressant medication. Selective serotonin reuptake inhibitors (SSRIs) have
become first-line treatment for pharmacotherapy for major depression. They are
effective and have few serious side effects or drug interactions. They are also very
safe in overdose. Weight gain and sexual problems are two of the most common
side effects and may lead to discontinuation of these medications.

The FDA has issued what is called "a black box warning" for all antidepressants.
This is a class warning for these medications and brings the warning that their use
may be associated with an increased frequency and severity of suicidal ideas.
Patients should be warned to call their physician right away if they start to have
thoughts of suicide or feel extremely restless.

GI side effects like diarrhea or queasiness, can occur with SSRIs but should pass
in several days. Patients should be reminded if they have severe side effects to
just stop the medication and call the physician right away.

Patients should be informed that it can take 4-6 weeks to begin to see
improvement in depressive symptoms after starting an anti-depressant. When this
is not specifically mentioned, patients will often stop their anti-depressant
medication after a few doses because they think it is not working.

After a single episode of depression, there is always a risk of recurrence. Lifetime

use of anti-depressants is usually recommended for individuals with 2 or more
relapses of their depression.

In this scenario, Mr. Kish initially does not meet criteria for admission to the

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 hospital. Most patients with depression are treated as outpatients. Exceptions to
this would be patients who are actively suicidal, homicidal or unable to care for
themselves.

Counseling or psychotherapy can be as effective as medication for mild to

moderate depression. Currently, counseling or psychotherapy is most commonly
done by psychologists or trained counselors, rather than psychiatrists. Many
patients lack insurance coverage for more than a few sessions, but this option
should be offered to most patients. Some studies show that medications in
combination with psychotherapy have the best and the longest-lasting efficacy.

The most important consideration for referral to a psychiatrist is the worsening of

the clinical condition with the development of suicidal ideas and or plans. This
development makes the situation a medical emergency with serious
considerations about hospitalization and changes in treatment plan. Manic and
psychotic symptoms are best evaluated and treated by mental health
professionals, whereas medication side effects can often be addressed by a
primary care physician.

Electroconvulsive therapy was first introduced for the treatment of depression in

the 1930s. In electroconvulsive therapy, electrodes are applied to the scalp to
induce seizure activity. ECT is felt to work by increasing cortical GABA, increasing
serotonergic function and altering functional brain activation. ECT is effective in
the treatment of depression, especially for patients who have a depression with
psychotic features. There is a remission rate of between 20-80%. Although it is
probably more efficacious than antidepressants, it is reserved for those individuals
who have failed medication management because of the side effects associated
with ECT. Side effects that are most concerning are retrograde amnesia. There is a
relative contraindication to use of ECT in individuals with unstable cardiac and
cerebrovascular disease.

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