Chronic fatigue is relatively common, but criteria-based chronic fatigue syndrome (CFS) is rare. Fatigue is defined as severe mental and physical exhaustion that differs from somnolence or lack of motivation and is not attributable to exertion or diagnosable disease. Chronic fatigue is defined as persistent or relapsing fatigue lasting 6 or more consecutive months. CFS is character- ized by severe disabling fatigue lasting more than 6 months and symptoms that feature impairments in concentration and short-term memory, sleep distur- bances, and musculoskeletal pain. About 24% of pa- tients complain of fatigue.
I. Common causes of chronic fatigue
A. The differential diagnosis of fatigue includes many
infections, malignancies, endocrinopathies, and connective tissue disease. The psychiatric ill- nesses include depression, anxiety, bipolar dis- ease, and somatoform and psychotic disorders. Depression is one of the most common underlying diagnoses when fatigue is a primary complaint.
B. Anxiety. Both depression and anxiety tend to be
accompanied by sleep disturbance symptoms. Anemia characteristically will cause a more gener- alized physical fatigue without sleep disturbances. Asthma and other lung diseases are common causes of fatigue.
Common causes of fatigue
Diagnosis Frequency in
primary care
Fatigued pa- tients (%)
Depression Very common 18 Environment (life- style) Very common 17 Anxiety, anemia, asthma Very common 14
Diabetes Very common 11 Infections Common 10 Thyroid, tumors Common 7 Rheumatologic Common 5 Endocarditis, car-
diovascular Common 8 Drugs Common 5
C. Diabetes should be considered in the obese
patient with fatigue. Hypothyroidism and hyperthyroidism are easily treatable causes of fatigue. Tumors and other malignancies may cause tiredness. Many infections cause fatigue, including viruses, tuberculosis, Lyme disease, and HIV infection.
D. Rheumatologic disorders, including rheumatoid
arthritis, systemic lupus erythematosus and fibromyalgia, are common causes of fatigue.
E. Endocarditis is a very rare cause of fatigue asso-
ciated with valvular and other cardiovascular diseases.
F. Drugs that may cause fatigue including analgesics,
psychotropics, antihypertensives, and antihista- mines. Over-the-counter medications and sub- stance abuse (caffeine, alcohol, and illicit drugs) may cause fatigue.
II. Clinical evaluation
A. Evaluation of chronic fatigue should exclude
diseases associated with fatigue. The time of onset of symptoms and the nature of the fatigue should be determined. Chronic fatigue syndrome is char- acterized by fatigue that is typically present throughout the day (even upon awakening), wors- ens with exercise, and is not improved with rest.
B. Fever, chills, night sweats, weight loss or anorexia
may be seen in chronic fatigue syndrome; how- ever, infectious disease or malignancy should also be considered. Confusion and cognitive difficulties are reported by nearly all chronic fatigue syndrome patients.
C. Headaches, myalgias, arthralgias, and painful
adenopathy are common complaints in chronic fatigue syndrome, although the presence of arthri- tis may also suggest connective tissue diseases. Anhedonia is suggestive of depression.
D. Recent travel, insect bites, tick exposure, skin
rashes, and use of prescription and over-the- counter drugs should be sought.
E. Physical examination. Specific physical findings
s u c h a s n o n e x u d a t i v e p h a r y n g i t i s , lymphadenopathy, skin rashes, muscle tenderness and orthostatic hypotension are often seen in chronic fatigue syndrome patients. The Romberg test and tandem gait test may be abnormal in up to 20% of chronic fatigue syndrome patients.
Criteria for chronic fatigue syndrome
Clinically evaluated, unexplained, persistent or relapsing chronic fatigue of new or definite onset; not the result of ongoing exertion; not substantially alleviated by rest; and causes substantial reduction in previous levels of occupa- tional, educational, social, or personal activities; and Occurs concomitantly with four or more of the following symptoms, all of which must have persisted or recurred during 6 or more consecutive months of illness and must not have predated the fatigue:
Short-term memory or concentration impairment Sore throat
Tender cervical or axillary lymph nodes
Muscle pain or multijoint pain without joint swelling or redness
Headaches of a new type, pattern, or severity Unrefreshing sleep
Laboratory evaluation of chronic fatigue For all patients
Complete blood cell count with differential Erythrocyte sedimentation rate Urinalysis
Other tests based on findings
Thyroid stimulating hormone Blood Chemistry levels:
Alanine aminotransferase Aspartate aminotransferase Blood urea nitrogen Electrolytes Glucose
Heterophil antibody test (Monospot) Serologic studies for Lyme or HIV antibody titers
III. Management of the fatigued patient
A. Regular exercise will improve functional capacity,
mood, and sleep. Regular sleep habits should be advised. In those complaining of depressive symptoms or sleep disturbance, an antidepres- sant or sleep hypnotic is indicated. A sedating antidepressant, such as amitriptyline (Elavil) 25 mg qhs, may be helpful for complaints of insom- nia or restlessness. If the primary complaints are hypersomnia and psychomotor retardation, a selective serotonin reuptake inhibitor is indicated.
B. For physical symptoms such as headaches,
myalgias, or arthralgias, nonsteroidal anti-inflam- matory agents may be helpful. Therapies for which no effectiveness has been demonstrated in CFS include vitamins, acyclovir, gamma globulin, folic acid, cyanocobalamin, and magnesium.
C. Antidepressants
1. Selective serotonin reuptake inhibitors (SSRIs)
are the drugs of choice. Fluoxetine (Prozac), paroxetine (Paxil), sertraline (Zoloft), and fluvoxamine (LuVox) are effective in reducing fatigue, myalgia, sleep disturbance, and de- pression.
2. For the patient who has significant difficulty
with insomnia or with pain, paroxetine at bed- time is recommended because it is mildly sedating. Fluoxetine is useful in patients who complain of lack of energy because it has activating properties. Fluoxetine often im- proves cognitive functioning, especially con- centrating ability.
3. Initial dosage should be low because many
CFS patients are sensitive to side effects.
a. Fluoxetine (Prozac) 20 mg PO qAM; 20-40
mg/d [20 mg].
b. Paroxetine (Paxil) 10 mg qAM; increase as
needed to max of 40 mg/d. [10, 20, 30, 40 mg].
c. Fluvoxamine (LuVox) 50-100 mg qhs; max
300 mg/d [50, 100 mg]
d. Sertraline (Zoloft) 50-100 mg PO qAM [50,
100 mg].
D. Omega-3 and omega-6 fatty acids, in the form
of fish oil supplements, may bring some improve- ment.
IV. Prognosis. CFS is a chronic illness, but 40-60% of
patients improve within1-3 years after diagnosis. The mean duration of illness prior to diagnosis is 52.6 months.