What is fatigue?

Quick Answer
A general symptom of tiredness, malaise, depression, and sometimes anxiety associated with many diseases and disorders; in some cases, no specific cause can be found.
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Causes and Symptoms

Almost all people suffer from fatigue at some point in their lives. It is a nonspecific complaint including tiredness, lack of energy, listlessness, or malaise. Patients often confuse fatigue with weakness, breathlessness, or dizziness, which indicate the existence of other physical disorders. Rest or a change in the daily routine ordinarily alleviates fatigue in healthy individuals. Though normally short in duration, fatigue occasionally lasts for weeks, months, or even years in some individuals. In such cases, it limits the amount of physical and mental activity in which the person can participate.

Long-term fatigue can have serious consequences. Often, patients begin to withdraw from their normal activities. They may withdraw from society in general and may gradually become more apathetic and depressed. As a result of this progression, a patient’s physical and mental capabilities may begin to deteriorate. Fatigue may be aggravated further by a reduced appetite and inadequate nutritional intake. Ultimately, these symptoms lead to malnutrition and multiple vitamin deficiencies, which intensify the fatigue state and trigger a vicious circle.

This fatigue cycle ends with a person who lacks interest and energy. Such patients may lose interest in daily events and social contacts. In later stages of fatigue, they may neglect themselves and lose track of their goals in life. The will to live and fight decreases, making them prime targets for accidents and repeated infections. They may also become potential candidates for suicide.

Physical and/or mental overactivity commonly cause recent-onset fatigue. Management of such fatigue is simple: Adequate physical and mental relaxation typically relieve it. Fortunately, many persistent fatigue states can be easily diagnosed and successfully treated. In some cases, however, fatigue does not respond to simple measures.

Fatigue can stem from depression. Depressed individuals often reflect boredom and a lack of interest, and frequently express uncertainty and anxiety about the future. These people usually appear “down.” They may walk slowly with their head down, slump their shoulders, and sigh frequently. They often take unusually long to respond to questions or requests. They also show little motivation. Depressed individuals typically relate feelings of dejection, sadness, worthlessness, or helplessness. Often, they complain of feeling tired when they wake up in the morning, and no amount of sleep or rest improves their condition. In fact, they feel weary all day and frequently complain of feeling weak. They often have poor appetites and sometimes lose weight. Once these patients are questioned by a physician, however, it may become apparent that their state of fatigue actually fluctuates. At times they feel exhausted, while at other times (sometimes only minutes later) they feel refreshed and full of energy.

Other manifestations of depression include sleep disorders (particularly early morning waking), reduced appetite, altered bowel habits, and difficulty concentrating. Depressed individuals sometimes fail to recognize their condition. They may channel their depression into physical complaints such as abdominal pain, headaches, joint pain, or vaguely defined aches and pains. In older people, depression sometimes manifests itself as impaired memory.

Anxiety, another major cause of fatigue, interferes with the patient’s ability to achieve adequate mental and physical rest. Anxious individuals often appear scared, worried, or fearful. They frequently report multiple physical complaints, including neck muscle tension, headaches, palpitations, difficulty in breathing, chest tightness, intestinal cramping, and trouble falling asleep. In some cases, both depression and anxiety may be present simultaneously.

Medications also constitute a major cause of fatigue. Most drugs—prescription, over-the-counter, or recreational—can cause fatigue. Medications for sleep, antidepressants, antianxiety medications, muscle relaxants, allergy medications, cold medications, and certain blood pressure medications can lead to problems with fatigue.

An excessive intake of stimulants, paradoxically, sometimes leads to easy fatigability. Stimulants can interfere with proper sleeping habits and relaxation. Common culprits include caffeine and medications (such as some diet pills and nasal decongestants) that can be purchased without a prescription. Recreational drugs can also contribute to chronic fatigue. Depending on their tendencies, they function to cause fatigue in much the same way as the prescription and over-the-counter drugs already discussed. Cocaine and amphetamines, for example, act as stimulants. Narcotics such as heroin and barbiturates (downers) possess strong sedative qualities. Alcohol consumption in an attempt to escape loneliness, depression, or boredom may further exacerbate a sense of fatigue. Alcohol produces fatigue in two ways. It has sedative qualities, and it also intensifies the sedative effects of other medications, if taken with them.

Other drugs that may induce fatigue include diuretics and those that lower blood pressure. These medications increase the excretions of many substances through the kidneys. If inappropriately given or regulated, these drugs may alter the blood concentration of other medications taken concurrently.

Painkillers can lead to fatigue in a different way. In some individuals, they irritate the lining of the stomach and cause it to bleed. Such bleeding usually occurs in small amounts and goes unnoticed by the patient. This slight blood loss can gradually lead to anemia and fatigue.

Medications are particularly likely to cause fatigue in elderly individuals. With many drugs, their elimination from the body through metabolism or excretion may decrease with age. This often leads to higher drug concentrations in the blood than intended, resulting in a state of constant sedation and lethargy. Also, elderly individuals’ brains may be more sensitive to sedation than those of younger individuals. Finally, the elderly tend to take more medication for more illnesses than younger adults. The additive side effects of multiple medicines can contribute to fatigue problems.

Sleep deprivation or frequent sleep interruptions lead to fatigue. A change in environment can induce sleep disorders, especially if accompanied by unfamiliar noises, excessive lighting, uncomfortable temperatures, or an excessive degree of humidity or dryness. Total sleep time may be adequate under such conditions, but quality of sleep is usually poor. Nightmares can also interrupt sleep, and if numerous and recurring, they also cause fatigue.

Some sleep interruptions are not so readily apparent. In sleep apnea, a specific and increasingly diagnosed sleep disorder, the patient temporarily stops breathing while sleeping. This results in reduced oxygen levels and increased carbon dioxide levels in the blood. When a critical level is reached, the patient awakens briefly, takes a few deep breaths, and then falls asleep again. Many episodes of sleep apnea may occur during the night, making the sleep interrupted and less refreshing than it should be. The next day, the patient often feels tired and fatigued but may not recognize the source of the problem. Obstructive sleep apnea normally develops in grossly overweight patients or in those with large tonsils or adenoids. Patients with obstructive sleep apnea usually snore while sleeping, and typically they are unaware of their snoring and sleep disturbance.

A number of diseases can lead to easy fatigability. In most illnesses, rest relieves fatigue and individuals awake refreshed after a nap or a good night’s sleep. Unfortunately, they also tire quickly. Unlike psychogenic fatigue or fatigue induced by drugs, disease-related fatigue is not usually the patient’s main symptom. Other symptoms and signs frequently reveal the underlying diagnosis. Individuals who suffer from severe malnutrition, anemia, endocrine system malfunction, chronic infections, tuberculosis, Lyme disease, bacterial endocarditis (a bacterial infection of the valves of the heart), chronic sinusitis, mononucleosis, hepatitis, parasitic infections, and fungal infections may all experience chronic fatigue.

In early stages of acquired immunodeficiency syndrome (AIDS), fatigue may be the only symptom. Persons at high risk for contracting the human immunodeficiency virus (HIV)—those with multiple sexual partners, those who have unprotected sex, those with a history of blood transfusion, or intravenous drug users—who complain of persistent fatigue should be tested for HIV infection.

Abnormalities of mineral or electrolyte concentrations—potassium, sodium, chloride, and calcium are the most important of these—may also cause fatigue. Such abnormalities may result from medications (diuretics are frequently responsible), diarrhea, vomiting, dietary fads, and endocrine or bone disorders.

Some less common medical causes of chronic fatigue include dysfunction of specific organs such as kidney failure or liver failure. Allergies can also produce chronic fatigue. Cancer can cause fatigue, but other symptoms usually surface and lead to a diagnosis before the patient begins to notice chronic weariness.

Treatment and Therapy

When an individual’s fatigue persists in spite of adequate rest, medical help becomes necessary in order to determine the cause. Common diseases known to be associated with fatigue should be considered. Initially, the physician makes detailed inquiries about the severity of the fatigue and how long ago it started. Other important questions include whether it is progressive, whether there are any factors that make it worse or relieve it, or whether it is worse during specific times of the day. An examination of the patient’s psychological state may also be necessary.

The physician should ask about the presence of any symptoms that occur along with the general sense of fatigue. For example, breathlessness may indicate a cardiovascular or respiratory disease. Abdominal pain might arouse the suspicion of a gastrointestinal disease. Weakness may point to a neuromuscular collagen disease. Excessive thirst and increased urine output may suggest diabetes mellitus, and weight loss may accompany metabolic or endocrinal abnormalities, chronic infections, or cancer.

Whether they have been prescribed by a physician or purchased over the counter, the medications taken regularly by a patient should be reviewed. The doctor should also inquire about alcohol and tobacco use and dietary fads. A thorough physical examination may be required. During an examination, the doctor sometimes uncovers physical signs of fatigue-inducing diseases. Blood tests and other laboratory investigations may also be needed, especially because a physical examination does not always reveal the cause.

Often, however, despite an extensive workup, no specific cause for the persistent fatigue appears. At this stage, the diagnosis of chronic fatigue syndrome should be considered. To fit this diagnosis, patients must have several of the symptoms associated with this syndrome. They must have complained of fatigue for at least six months, and the fatigue should be of such an extent that it interferes with normal daily activities. Since many of the symptoms associated with chronic fatigue syndrome overlap with other disorders, these other fatigue-inducing conditions must be considered and ruled out.

To fit the diagnosis of chronic fatigue syndrome, patients must have at least six of the classic symptoms. These include a mild fever and sore throat, painful lymph nodes in the neck or axilla, unexplained generalized weakness, and muscle pain or discomfort. Patients may describe marked fatigue lasting for more than twenty-four hours that is induced by levels of exercise that would have been easily tolerated before the onset of fatigue. They may suffer from generalized headaches of a type, severity, or pattern that is different from headaches experienced before the onset of chronic fatigue. Patients may also have joint pain without swelling or redness and neuropsychologic complaints such as a bad memory and excessive irritability. Confusion, difficulty in thinking, inability to concentrate, depression, and sleep disturbances are also on the list of associated symptoms.

No one knows the exact cause of chronic fatigue syndrome. Researchers continue to study the disease and come up with hypotheses, though none have proven entirely satisfactory. One theory argues that since patients with chronic fatigue syndrome appear to have a reduced aerobic work capacity, defects in the muscles may cause the condition. This, however, constitutes only one of many theories concerning the syndrome and its origin.

Many patients with chronic fatigue syndrome relate that they suffered from an infectious illness immediately preceding the onset of fatigue. This pattern causes some scientists to suspect a viral origin. Typically, the illness that precedes the patient’s problems with fatigue is not severe, and resembles other upper respiratory tract infections experienced previously. The implicated viruses include the Epstein-Barr virus, Coxsackie B virus, herpes simplex virus, cytomegalovirus, human herpesvirus 6, and the measles virus. It should be mentioned, however, that some patients with long-term fatigue do not have a history of a triggering infectious disease before the onset of fatigue.

Patients with chronic fatigue syndrome sometimes have a number of immune system abnormalities. Laboratory evidence exists of immune dysfunction in many patients with this syndrome, and there have been reports of improvement when immunoglobulin (antibody) therapy was given. The significance of immunological abnormalities in chronic fatigue syndrome, however, remains uncertain. Most of these abnormalities do not occur in all patients with this syndrome. Furthermore, the degree of immunologic abnormality does not always correspond with the severity of the symptoms.

Some researchers believe that the acute infectious disease that often precedes the onset of chronic fatigue syndrome forces the patient to become physically inactive. This inactivity leads to physical deconditioning, and the progression ends in chronic fatigue syndrome. Experiments in which patients with chronic fatigue syndrome were given exercise testing, however, do not support this theory completely. In the case of physical deconditioning, the heart rates of patients with chronic fatigue syndrome should have risen more rapidly with exercise than those without the syndrome. The exact opposite was found. The data were not determined consistent with the suggestion that physical deconditioning causes chronic fatigue syndrome.

A high prevalence of unrecognized psychiatric disorders exists in patients with chronic fatigue, especially depression. According to a 2012 article in American Family Physician, depression affects approximately 39 to 47 percent of chronic fatigue syndrome patients. Yet a critical question remains unanswered concerning chronic fatigue syndrome: Are patients with this syndrome fatigued because they have a primary mood disorder, or has the mood disorder developed as a secondary component of the chronic fatigue syndrome?

No completely satisfactory treatment exists for chronic fatigue syndrome. A group of researchers using intravenous immunoglobulin therapy met with varying degrees of success, but other investigators could not reproduce these results. Other therapeutic trials used high doses of medications such as acyclovir, liver extract, folic acid, and cyanocobalamine. A mixture of evening primrose oil and fish oil was also administered with some degree of success. Claims have also been made that patients administered magnesium sulfate improved to a larger extent than those receiving a placebo. Other therapeutic options include cognitive behavioral therapy, programs of gradually increasing physical activity, analgesics, nonsteroidal anti-inflammatory drugs (NSAIDs), and antidepressants. Finally, a number of self-help groups exist for chronic fatigue sufferers.

The prognosis and natural history of chronic fatigue syndrome are still poorly defined. Chronic fatigue syndrome does not kill patients, but it does significantly decrease the quality of life for sufferers. For the physician, management of this syndrome remains challenging. In addition to correcting any physical abnormalities present, the physician should attempt to find an activity that interests the patient and encourage him or her to become involved in it.

Perspective and Prospects

Fatigue is generally considered a normal bodily response, protecting the individual from excessive physical and mental activity. After all, the normal levels of performance for individuals who do not rest usually decline. In the case of overactivity, fatigue should be viewed as a positive warning sign. Using relaxation and rest (both mental and physical), the individual can often alleviate weariness and optimize performance.

In some cases, however, fatigue does not derive from physical or mental overactivity, nor does it respond adequately to relaxation and rest. In these instances, it interferes with an individual’s ability to cope with everyday life and enjoy usual activities. The patient begins referring to fatigue as the reason for not participating in normal physical, mental, and social activities.

Unfortunately, physicians, health care professionals, society, and even the patients themselves dismiss fatigue as a trivial complaint. As a result, sufferers seek medical help only after the condition becomes advanced. This dangerous, negative attitude can delay the correct diagnosis of the underlying pathology and threaten the patient’s chances for a quick recovery.

The diagnosis and management of chronic fatigue syndrome prove challenging for both physician and patient. It is important to note that chronic fatigue syndrome often stems from nonmedical causes. While the possibility of a serious medical illness should be addressed, illness-related fatigue usually occurs along with other, more prominent symptoms. The causes of chronic fatigue syndrome are numerous and can take time to define. Patients need to answer all questions related to their complaints as thoroughly and accurately as possible, so that their physicians can reach accurate diagnoses using the minimum number of tests. Extensive testing for rare medical causes of fatigue can become extraordinarily expensive and uncomfortable, so doctors select the tests that they are ordering cautiously. They must balance the benefit, the cost, and the risk of each test to the patient. Such decisions should be based on their own experience and on the available data.

Open communication between the patient and doctor is of paramount importance. It ensures a correct diagnosis, followed by the most effective treatment. Follow-up visits and reassurance may be the best therapy in many cases. Professional counselors can offer assistance with fatigue-inducing psychological disorders. Examination of sleep and relaxation habits can reveal potential problems, and steps can be taken to ensure adequate rest.

Persistent fatigue should not be regarded lightly, and serious attempts should be made to determine its underlying causes. In this respect, it may be appropriate to recall one of Hippocrates’ aphorisms, “Unprovoked fatigue means disease.”


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