  Chronic fatigue syndromeHighlightsCauses
Diagnosis
Treatment
IntroductionChronic fatigue syndrome (CFS), sometimes called immune dysfunction syndrome or myalgic encephalomyelitis (in Europe), is not a new disorder. In the 19th century the term neurasthenia, or nervous exhaustion, was applied to symptoms resembling CFS. In the 1930s through the 1950s, outbreaks of disease marked by prolonged fatigue were reported in the United States and many other countries. Beginning in the early- to mid-1980s, interest in chronic fatigue syndrome was revived by reports in America and other countries of various outbreaks of long-term debilitating fatigue. Unexplained chronic fatigue describes fatigue that lasts for more than 6 months, impairs normal activities, and has no identifiable medical or psychological problems to account for it. In addition to fatigue, people may complain of other problems, such as difficulty with memory or concentration, headaches, or sore muscles or joints. The symptoms of CFS may be categorized as follows:
Although the exact causes of CFS are not known, researchers think infection, genetics, hormonal imbalances, and chemical toxins play roles in different patients. Risk FactorsIn studies of large patient groups, 15 - 27% of people complain of long-term fatigue, but the majority of this fatigue can be explained by other medical or psychological problems. According to surveys, chronic fatigue syndrome (CFS) itself affects more than four out of every 1,000 Americans. CFS occurs in both sexes, at all ages, and in all racial and ethnic groups. The Centers for Disease Control and Prevention estimates 1 million people in the U.S. have the disease, but only 20% of people with CFS may be properly diagnosed. Nevertheless, the true prevalence of CFS is very difficult to determine, since an accurate diagnosis is hard to obtain. People ages 40 - 50 most often experience chronic fatigue. Studies have found that four out of five people with CFS are women, although a woman's symptoms do not appear to be more severe symptoms than those of men with the disorder. Children and adolescents are not immune to CFS. Most studies indicate that girls are more likely than boys to develop CFS, although one study found the incidence of the syndrome to be equal in children among the genders. The link between psychological disorders and chronic fatigue syndrome is problematic because so many of the symptoms overlap. The rates of depression are very high in CFS patients, possibly higher than in patients with other conditions (notably fibromyalgia and multiple chemical sensitivity). Studies report that most children and adolescents with CFS have psychiatric disorders. Psychological factors during childhood may increase susceptibility for later CFS, although these factors are not consistent. Studies have not found any consistent association between emotional or personality disorders and CFS to explain any causal role. Some psychological factors may, however, serve as a risk factor for CFS. Depression, in any case, is very common in the general population. It affects up to one-fifth of all Americans at some point in their lives, and most depressed people feel fatigued. There is some evidence that stress may be a trigger for CFS in people genetically at risk for the disease. A number of conditions overlap or coexist with chronic fatigue syndrome and have similar symptoms. Patients with CFS may also have a diagnosis of fibromyalgia, multiple chemical sensitivity, or both. It is not clear whether these conditions or others are risk factors for CFS, are direct causes, have common causes, or have no relationship at all with CFS. Fibromyalgia. Fibromyalgia causes prolonged fatigue and widespread muscle aches. It is the disease most often confused with CFS. The two conditions also commonly appear together. In fact, many experts believe fibromyalgia is simply another variant of chronic fatigue syndrome or different manifestations of the same disease. CFS patients experience severe fatigue, whereas fibromyalgia patients experience more pain. One hypothesis proposes that the connection between the two conditions may be found in central sensitization, which is thought to cause fibromyalgia and may also cause CFS. A characteristic feature of fibromyalgia is the existence of at least 11 distinct sites of deep muscle tenderness that hurt when touched firmly. The sites often include the following:
Some patients with CFS exhibit similar tender pressure points. Recurrent sore throat, headache, low fever, and depression are also common symptoms of fibromyalgia. Like CFS, fibromyalgia is chronic and not curable. Multiple Chemical Sensitivity. Multiple chemical sensitivity (MCS) is a term now used to describe a condition in which certain chemicals are believed to cause symptoms similar to CFS in some people. It has also been observed in people with CFS. The following proposed criteria can help recognize people with MCS:
Still, as with CFS and fibromyalgia, there is uncertainty as to whether MCS is an actual medical condition or is psychologically based. In one study, for example, CFS patients who believed their problem was chemically triggered were exposed to either an active chemical or a placebo (an inactive substance). Both groups reported symptoms, including those exposed only to the placebo. It should be noted that everyone is exposed to many chemicals on a daily basis, and it is very difficult to determine whether chemicals are responsible for specific symptoms. Post-ADD. Young adults who had attention deficit disorder as children can flip from hyperactivity to fatigue. Such patients have severe hypersomnolence (sleeping too much, sleeping at any time or anywhere). These patients respond well to psychostimulant medications. Eating Disorders. Eating disorders, notably bulimia and anorexia, have been observed in patients with CFS. The conditions often have overlapping risk factors, although it is unclear whether there is a causal relationship. Other Conditions that Commonly Coexist With CFS. A number of other conditions also often coexist with CFS and, in fact, occur at higher-than-average rates among CFS patients:
CausesTheories abound about the causes of chronic fatigue syndrome. Indeed, no primary cause has been found that explains all cases of CFS, and no blood tests or brain scans can definitively diagnose the condition. Convergence of Factors. A number of experts believe that CFS develops from a convergence of conditions that may include the following:
For example, the majority of patients report some preceding moderate-to-serious physical illness (such as a chronic viral infection) or emotional event (like an episode of depression). Some experts theorize that such events, alone or in combination, may interact with certain neurologic and genetic abnormalities to trigger the event. Still, it is not clear what sequence of events actually leads to the fatigue and other prominent symptoms of this disorder. Nor is there any specific brain or nervous system problem that experts can point to with assurance. Research indicates that CFS is more common among identical twins (who share the same genes) than fraternal twins (who share only some genes). Inheritance, then, may play a role in roughly 30 - 50% of cases, similar to the influence thought to occur in depression or alcoholism, although specific genes have not yet been identified. New evidence suggests genes involved in the body's response to stress may play key roles in CFS. A series of 14 articles published in 2006 linked CFS with genes involved in the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system. The researchers were able to locate a common variation of DNA sequences that predicted CFS with 76% accuracy. The genes control response to trauma, injury, and other stressful events. Nevertheless, the researchers were unable to find genetic markers of CFS or to determine how the genetic variations influenced symptoms. In 2005, English researchers found that people with CFS are more likely than people without CFS to have human leukocyte antigen (HLA) class II alleles, variations that produce antibodies to certain immune factors. Another British study of people with CFS found alterations in 16 specific genes involved with immune function, communication between cells, and transfer of energy to cells. Abnormal levels of certain chemicals regulated in the brain system known as the hypothalamus-pituitary-adrenal (HPA) axis have been proposed as a cause of CFS. This system controls important functions, including sleep, response to stress, and depression. Of particular interest to researchers are the following chemicals and other factors controlled by the HPA axis:
However, it is still not clear whether any of these changes are causes of chronic fatigue syndrome, or merely findings in some patients. Because most of the features of CFS resemble those of a lingering viral illness, many researchers have focused on the possibility that a virus or some other infectious agent causes the syndrome in some cases. Still, not all CFS patients show signs of infection. Although experts have long been divided on whether infections play any role in this disorder, subtypes of viral-related and non-viral CFS may both exist. Viruses. The theory that CFS has a viral cause is not based on hard evidence, but on various observations that suggest an association, such as the following:
Some researchers are suggesting that changes in normally harmless bacteria found in the intestine may play a role in the development of CFS. Evidence suggesting that some CFS cases may not be due to a virus includes the following:
CFS has sometimes been referred to as the "chronic fatigue immune dysfunction syndrome." A number of studies have found many irregularities of the immune system. Some components appear to be over-reactive, while others appear to be under-reactive, but no consistent picture has emerged to explain CFS as a disease of the immune system. Allergies. Some studies have reported that a majority of CFS patients have allergies to foods, pollen, metals (such as nickel or mercury), or other substances. One theory is that allergens, like viral infections, may trigger a cascade of immune abnormalities leading to CFS. (Most allergic people do not have CFS.) Autoimmune Abnormalities. The risk profile for chronic fatigue syndrome is similar to the risk profiles for a number of autoimmune diseases. Studies are inconsistent, however, in reporting the presence of autoantibodies (antibodies that attack the body's own tissues) in CFS, and the disease is unlikely to be due to autoimmunity. Studies have observed that some patients who fit the strict criteria for chronic fatigue syndrome also have symptoms of a condition known as neurally mediated hypotension (NMH). NMH causes a dramatic drop in blood pressure when a person stands up, even for as short a time as 10 minutes. Its immediate effects can be lightheadedness, nausea, and fainting. However, not all CFS patients experience NMH, and studies have reported no higher incidence of NMH in chronic fatigue patients. Psychological, personality, and social factors are strongly associated with chronic fatigue in most patients. The complex relationship between physical and emotional factors has yet to be fully understood, however. Studies have not found any consistent association between emotional or personality disorders and CFS to explain a causal role. Psychological factors, then, are unlikely to be a primary cause of CFS. They may play a role in increasing susceptibility to the disorder. Certainly, in many cases, CFS promotes psychological and social dysfunction. Overall, doctors are increasingly adopting the view that CFS is probably a disease category that includes a range of subtypes, in the same way that cancer is a broad term within which numerous specific forms occur. Mounting evidence suggests that different subtypes of CFS have different causes and manifestations, and that these various types require different treatment approaches. Research on subgroups of CFS is underway, but it is still in the very early stages. To date, however, clinical experience and limited data suggest that subgroups of CFS may include the following:
Observations that different treatments work for select patients appear to support the idea that subtypes of CFS require distinct approaches. The existence of subgroups may also explain why CFS researchers are frequently unable to replicate their results in subsequent studies; patient selection in studies to date has not reflected such careful discrimination. Researchers are now, however, working to define the subgroups of CFS and identify which treatments are most effective for each. It should be noted that while the subgroup theory is interesting, in some cases the differences among patient populations may also reflect stages of disease. For instance, in the initial stages of the disease, many patients are symptomatic and have particular psychological symptoms, including alarm, denial, and anger. In contrast, patients in later phases of the disease typically have learned to cope better with their symptoms and have a degree of acceptance. Patients' mental and emotional status may have biological consequences that bear on their physical symptoms. Such a relationship is not yet documented in CFS patients, however, and remains subject to research. Sudden- and Gradual-Onset CFS. One interesting theory is that CFS can be categorized as either sudden- or gradual onset, with each subgroup having different causes. In over half of patients, the onset is sudden, while the remaining patients have a slow onset. Some experts believe that sudden-onset CFS may be triggered by a virus or neurologic abnormality, while gradual-onset CFS might have a psychological or other cause. Supporting this theory was a study that looked at MRI scans of the brains of CFS patients who didn't have an accompanying psychiatric problem, and showed small injuries suggesting either a viral infection or neurologic problem. Still other experts believe that in some cases, gradual-onset CFS may be traced to cognitive disorders that were present during childhood, but went unrecognized until symptoms advanced into adulthood. DiagnosisIt is very difficult to diagnose chronic fatigue syndrome. Even experts do not have a clear definition of what chronic fatigue actually is or what mechanisms in the brain or nervous system are responsible for it. The best diagnostic approach is to determine if the patient matches the criteria for CFS and to rule out other possible causes of symptoms. In May 2006, the Centers for Disease Control and Prevention (CDC) released a revised definition for Chronic Fatigue Syndrome based on a consensus of many of the leading CFS researchers and doctors (including input from patient group representatives). In the revised definition, chronic fatigue syndrome is considered a subset of chronic fatigue, a broader category defined as unexplained fatigue that lasts for 6 months or longer. Chronic fatigue is considered a subset of prolonged fatigue, which is defined as fatigue that lasts for 1 month or more. Unexplained chronic fatigue can be classified as CFS if the patient meets the following criteria:
Any other abnormality found during an exam or other tests that could explain CFS symptoms must be resolved before further attempting to classify the condition. In 2007, the National Institute for Health and Clinical Excellence (NICE) released new guidelines for the diagnosis and management of CFS in adults and children. According to these guidelines, CFS may be diagnosed if the person has disabling fatigue that starts suddenly, lasts a long time, keeps coming back, and can't be explained by another condition. People with CFS also can have the following symptoms:
After ruling out other possible causes, the doctor should consider a diagnosis of CFS if symptoms have lasted for 4 months in adults or 3 months in children. Children should be diagnosed by a pediatrician. A doctor should first take a careful personal and family medical history, which may include a psychological profile, as well as perform a thorough physical examination. Patients should be prepared to answer questions such as:
The doctor may also ask about any changes in weight or request a patient to monitor morning and afternoon body temperatures. Patients should report any drugs they are taking, including vitamins and over-the-counter or herbal medications. Standard tests are typically recommended to rule out specific conditions that can cause persistent fatigue. These tests include:
No blood, urine, or other laboratory test can specifically diagnose CFS. If any test is abnormal, it is not useful for diagnosing CFS specifically, and the doctor should look for other causes of these abnormalities. That being said, research published in 2005 found that certain components in urine were unique in people with CFS, and may someday be considered biomarkers of the disease. Additionally, antibodies to Epstein-Barr virus and increased levels of isoprostanes -- markers of oxidative stress -- have been found in the blood of people with CFS. Among the many other common conditions that can lead to feelings of temporary exhaustion are the following:
In most of these cases, fatigue can be relieved with adequate rest. It is important to note that longstanding fatigue can be the harbinger of a serious medical or psychological problem. A number of more serious conditions may cause persistent fatigue and other symptoms of CFS and should be ruled out. Patients and doctors should not overlook these diseases, even if the conditions have been previously treated, because they may not have completely resolved or they may cause residual fatigue. Doctors can usually distinguish these diseases from CFS after a clinical evaluation and laboratory testing. Infectious Mononucleosis and Epstein-Barr Virus. Infectious mononucleosis is marked by fatigue and swollen glands. It primarily affects adolescents and young adults. Some patients may have lingering fatigue that lasts for many months and blood tests that indicate a persistence of the Epstein-Barr virus (EBV), which causes mononucleosis. Autoimmune Diseases. Some diseases, including systemic lupus erythematosus, multiple sclerosis, and rheumatoid arthritis, are caused by autoimmunity, a condition in which the person's immune system attacks the body's own tissues. The early symptoms of these conditions may mimic some of those that appear in CFS, such as muscle and joint pain and fatigue. These diseases, like CFS, also occur more often in women than in men. Most of these conditions can be confirmed with laboratory or x-ray/radiologic findings. However, some autoimmune diseases may evolve slowly, and even if a diagnosis of chronic fatigue syndrome is considered, doctors should keep track of any changes in symptoms over time in order to rule out these serious illnesses. Post-Lyme Disease Syndrome. Rarely, patients treated for a diagnosis of Lyme disease continue to have nonspecific symptoms, which can last for years after antibiotic treatment and that resemble symptoms of chronic fatigue syndrome. Psychosis and Severe Mental Disorders. The Centers for Disease Control (CDC), which set up the definitions in the U.S. for research in chronic fatigue syndrome, recognizes depression as one of the symptoms of CFS. However, according to the CDC, anyone with a history of major depression or other severe psychiatric disorders, including bipolar disorder and schizophrenia, does not meet the criteria for chronic fatigue syndrome. Symptoms of major depression include the following:
Major depression is likely to be responsible if a person has several of these symptoms and no physical symptoms (such as sore throat, aches and pains, or fever). The longer fatigue has continued without such physical symptoms, the more likely that the diagnosis is depression. Of note, a persistent form of minor depression called dysthymia may be more difficult to differentiate from CFS and may actually account for a subset of CFS cases. Dysthymia is characterized by many of the same symptoms that occur in major depression, but they are less intense and last much longer, at least two years. The symptoms of dysthymia have been described as a "veil of sadness" that covers most activities. Patients with depression and those with CFS generally perceive their illnesses differently:
Many previously healthy patients with CFS become depressed and anxious because they feel so exhausted all the time. CFS may also lead to highly stressful socioeconomic situations, such as social isolation and poverty, that can contribute to and even cause emotional disorders in susceptible individuals, which in turn can worsen CFS. Sleep Disturbances. Certain sleep disorders may cause persistent fatigue and can be confused with CFS:
Researchers have found that people with CFS have altered amounts of slow wave sleep, which could indicate a problem with sleep regulation. Non-restorative sleep and nighttime restlessness are the most common complaints of people with CFS. Conditions that Cause Joint Pain, Muscle Aches, or Both. A number of illnesses cause one or more of CFS symptoms, including arthritic symptoms, fever, and fatigue. Severe Obesity. People who are severely obese often have symptoms of chronic fatigue because of the stress imposed by the weight. People who are obese are also at particular risk for sleep apnea, which can confuse the diagnosis. Other Medical Conditions that Usually Rule Out CFS. Many diseases, both benign and serious, can fully explain prolonged or chronic fatigue, including:
Drugs and Alcohol. Fatigue is a side effect of many prescription and over-the-counter medications, such as antihistamines. In addition, dependency on or abuse of alcohol or illicit drugs may manifest as chronic fatigue. Medications should be considered as a possible cause of fatigue if an individual has recently started, stopped, or changed medicines. Withdrawal from caffeine can produce depression, fatigue, and headache. PrognosisThe physical severity of chronic fatigue syndrome varies. Most commonly, patients with CFS report that they have trouble fulfilling both home and work responsibilities. CFS sufferers typically work part-time. In extreme cases, patients are severely disabled and even bedridden. Such patients can do virtually nothing, including even light housework. Patients with CFS are more likely to lose their jobs, possessions, and support from friends and family than are people who have other conditions that cause fatigue. Most patients say that while fatigue is the most incapacitating symptom, mental impairment, such as an inability to concentrate or remember, is the most distressing symptom. The effects of CFS on mental functioning are complex, however. Some experts believe that the impaired mental functioning is due to depression, which is common in CFS patients. Some studies indicate that, although general intelligence is not impaired, CFS patients test lower in certain mental functions, particularly speed and efficiency in processing complex information, and that 40 - 60% have memory impairments. In such studies, this impaired mental function occurs regardless of the presence or absence of depression or other psychiatric disorders. Because the illness remains elusive and poorly defined, and there are few objective measures for recovery, experts have found it difficult to determine the long-term course of the disease. Many patients are not covered by insurance or have difficulty finding good care, so available statistics may be incorrect. Bearing these factors in mind, some studies have reported that more than half of patients who complain of chronic fatigue are still fatigued at 2 years. Although a variety of studies have attempted to identify factors that predict a more chronic or severe course, no clear conclusions can be made. Even if patients get progressively worse, however, the disorder is not fatal. Although children with symptoms of chronic fatigue have not been as rigorously studied as adults, limited evidence suggests that CFS can be significantly disabling in young people. Studies report that adolescents who meet the criteria for CFS also have greater anxiety, depression, and school absenteeism than their peers. Still, some studies indicate that children have a better prognosis than adults and that most will recover after 1 - 4 years. Several studies have indicated that cognitive-behavioral therapy is an effective treatment for adolescents with CFS. TreatmentThere is no proven or reliable cure for CFS, and no drug has been developed specifically for this disorder. Because CFS remains poorly understood, many patients have problems finding good care. Overall, the recommended strategy for treatment includes a combination of the following:
Patients with the best chance for improvement are those who remain as active as possible and who seek to have some control over the course of the disorder. Patients should choose physicians who are willing to consider the problem as a medical condition with psychiatric components. They should be very wary, however, if the physician recommends excessive and expensive treatments that may have serious adverse effects and that have no proven benefits. For patients with severe CFS that cannot be managed with lifestyle changes and standard medications, asking the physician about enrolling in any available clinical trials may be helpful. Cognitive-Behavioral Therapy CBT is designed to help CFS patients regain a sense of control, and is proving to have substantial benefits for some patients. Some experts believe that patients who are diagnosed with CFS should be referred to therapists trained in cognitive-behavioral therapy. (Psychoanalysis and other interpersonal psychological therapies, which are concerned with subconscious thoughts and early childhood memories, are not generally helpful for the CFS patient.) The Goals of Cognitive-Behavioral Therapy. The primary goals of cognitive-behavioral therapy (referred to below as just cognitive therapy) are to change any distorted perceptions that individuals have of the world and of themselves, and to change their behavior accordingly. For CFS patients, this means learning to think differently about their fatigue and to improve their ability to deal with stressful situations and manage their disorder. It can also help manage their sleep problems and find the appropriate activity levels for them. Cognitive therapy is particularly helpful in defining and setting limits, behaviors that are extremely important for these patients. The Procedure. CBT is usually performed over 6 - 20 sessions, each lasting about an hour. Patients are also given homework, which usually includes keeping a diary and attempting tasks that they have avoided because of negative attitudes. A typical cognitive therapy program may involve the following measures:
Using both self-observation and specific tasks, patients gradually shift their fixed ideas that they are helpless against the fatigue that dominates their lives. They move to the perception that fatigue is only one negative and, to a degree, a manageable experience among many positive ones. Success Rates. One review of CFS trials reported that, of all therapies available to CFS patients, only cognitive behavioral therapy (CBT) and graded exercise showed conclusive benefits. Although CBT doesn't appear to bring patients completely back to normal, research has found that people who used the therapy had higher mental health scores, and were able to walk faster and with less fatigue than those who didn't use CBT. A 2005 study found that cognitive therapy is an effective treatment for adolescents with CFS. Patients who received CBT reported improvements in fatigue, functional status, and school attendance. Not all studies support the benefits of cognitive therapy for CFS. It is important to note that different therapists may have different fundamental assumptions about CBT and may use different techniques. For instance, some therapists believe that CFS is purely a psychological problem and that patients must reject the notion of physical causes, abandon all reliance on assistive devices, and participate in challenging exercise programs. In contrast, other therapists do not attempt to change patients' underlying beliefs at all, but instead focus on helping patients conserve energy and better cope with the limitations of their illness. When considering CBT, patients and their families must be aware of such important differences. Regardless of whether specific organic causes of CFS are identified, the power of the mind to improve or oppose health problems is significant, and treatments that promote a positive outlook are beneficial for any disease. A number of studies have suggested that a graded exercise program, in which patients perform increasingly more intense levels of exercise tailored to their individual abilities, has benefits for many patients with CFS. Exercise is best performed in combination with cognitive behavioral therapy. Reports have found that 75% of CFS patients who were able to engage in exercise, particularly aerobic exercise, reported less fatigue and better daily functioning and fitness after a year. A 2004 review of clinical trials found that exercise therapy is beneficial for CFS, particularly when combined with patient education. Some patient groups and experts contend that such studies use only patients with less severe conditions and do not apply to many CFS patients. Many patients have severe conditions, and some are very incapacitated (such as being wheelchair bound). These patients are unlikely to undergo even graded exercise. All CFS patients, in fact, have a lower exercise capacity than healthy individuals, and over-exercising can intensify symptoms. Some patients experience profound fatigue following even modest exercise. It is the primary factor in perpetuating the low-activity levels observed in these patients. The following tips may be helpful for CFS patients when embarking on an exercise program:
Work with your health care provider to find a level of activity you can handle. Then gradually increase your activity level. Activity management should involve:
Although there is no evidence to support any specific dietary factors in CFS, patients should be sure to maintain a healthy diet that includes:
Stress Reduction Techniques. One panel of experts concluded that relaxation and stress-reduction techniques were helpful in managing chronic pain. These techniques also can help relieve the stress associated with the disease. They are not useful, however, as the primary treatment for CFS. A number of relaxation techniques are available:
Light Therapy. Patients with seasonal affective disorder (SAD) experience more depression during the winter, when the hours of sunlight decrease. With light therapy (phototherapy), the patient sits for about 30 minutes each day a few feet away from a box-like device that emits very bright fluorescent light (4,000 lux). Light therapy is best performed immediately after awakening in the morning. Some CFS patients don't have much improvement from light therapy. However, the treatment may still help some patients with CFS whose symptoms are similar to those of patients with seasonal affective disorder (SAD). Supportive Family and Groups. Having strong, supportive relationships with family and friends can help CFS patients get better. However, CFS patients should try not to impose unreasonable expectations on loved ones that cannot be met. Ongoing support groups with fellow patients may be very helpful. In one study, sharing experiences in a group therapy setting proved to be the most valuable component in treatment, and one that improved patients' coping abilities. MedicationsNo medications are specifically approved for the treatment of CFS. However, some may be useful for pain or other specific symptoms, or in cases where CFS may have a specific cause. Doctors generally use combinations of drugs to accomplish specific goals, such as medication at night to improve sleep and medication in the morning to improve cognition and energy. Treatment is very individualized. Nonsteroidal Anti-Inflammatory Drugs (NSAIDs). Patients with CFS may find relief using NSAIDs -- common pain relievers that reduce pain and swelling. Types of NSAIDs include aspirin, ibuprofen (Motrin, Advil, Nuprin), and naproxen (Aleve, Naprosyn, Naprelan, Anaprox). Although NSAIDs work well, long-term use can cause stomach problems, such as ulcers and bleeding. In April 2005, the FDA asked drug manufacturers of NSAIDs to include a warning label on their product that alerts users of an increased risk for cardiovascular events and gastrointestinal bleeding. Due to its proven cardiovascular benefits, aspirin was excluded from these labeling revisions. NSAIDs can also increase blood pressure, particularly among people already being treated for hypertension. (About 12 - 15% of elderly people take both an NSAID and an antihypertensive drug.) Piroxicam, naproxen, and indomethacin appear to pose the greatest risk of high blood pressure. Sulindac has the smallest effect. Other side effects of NSAIDs include:
NSAIDs can cause kidney damage. (The damage gets better once the patient stops using the drug.) People with high blood pressure, severe circulation disorders, or kidney or liver problems, as well as people taking diuretics or oral hypoglycemics, must be closely monitored if they need to use NSAIDs on a long-term basis. Because NSAIDs reduce blood clotting, NSAID users scheduled for surgery should stop taking those drugs a week before the operation. COX-2 Inhibitors (Coxibs). Coxibs block an inflammation-promoting enzyme called COX-2. This class of drugs was initially believed to work as well as traditional NSAIDs, but with fewer stomach problems. However, numerous reports of cardiovascular events, skin rashes, and other adverse effects prompted the FDA to re-evaluate the risks and benefits of the COX-2 drugs. Rofecoxib (Vioxx) and valdecoxib (Bextra) were withdrawn from the U.S. market following reports of heart attacks in patients taking the drugs. Celecoxib (Celebrex) was still available at the time of this report, but labeled with strong warnings and a recommendation that it be prescribed at the lowest possible dose for the shortest duration possible. Patients should ask their doctor whether the drug is appropriate and safe for them. Because of the association between depression and CFS, antidepressants are often tried, with varying degrees of success. Common side effects of many antidepressants include:
Virtually all antidepressants have complicated interactions with other drugs, and some are very serious. Tricyclic Antidepressants. Antidepressants known as tricyclics may be particularly helpful for CFS patients. For example, the tricyclic amitriptyline (Elavil) is known to relieve many of the symptoms of CFS, including sleeplessness and low energy levels. These drugs may provide benefits by promoting deep sleep and inhibiting pain pathways in the nervous system. Improvement in symptoms can take 3 - 4 weeks. Other tricyclics include doxepin (Sinequan), desipramine (Norpramin), nortriptyline (Pamelor), clomipramine (Anafranil), and imipramine (Tofranil, Janimine). Patients with CFS normally respond to much lower doses than those used to treat people with depression. In fact, many CFS patients cannot tolerate the higher doses commonly used to treat the psychiatric disorder. Like all medications, tricyclics must be taken as directed. Overdose can be life-threatening. Tricyclics should not be taken together with SSRIs, because of the possibility of dangerous side effects. Other Antidepressants. Newer, so-called designer SSRIs, including bupropion (Wellbutrin), nefazodone (Serzone), or mirtazapine (Remeron), affect combinations of different neurotransmitters, and some may have moderate benefits for CFS patients. For example, in one study, nefazodone improved mood, fatigue, and sleep disturbances. SSRIs. The popular antidepressants known as selective serotonin-reuptake inhibitors (SSRIs) may be helpful for the subgroup of CFS patients who experience significant depression. They include fluoxetine (Prozac), sertraline (Zoloft), and paroxetine (Paxil). Cymbalta (duloxetine) is a new antidepressant that is classified as a selective serotonin and norepinephrine reuptake inhibitor (SSNRI). In a 2006 UK study of 275 CFS patients, those treated with antidepressants recovered faster than those who did not receive the medication. SSRIs were found to be more effective than tricyclic antidepressants, producing improvements, including a reduction in fatigue, that were maintained at the 3-year follow-up. Psychostimulants. Psychostimulants may be helpful for a subgroup of patients with CFS who have cognitive problems, such as difficulty concentrating, memory problems, and other attention deficit disorder (ADD)-like characteristics. Psychostimulants include Dexamphetamine, Adderal, methylphenidate (Ritalin) and Ritalin-like drugs such as Focalin, Concerta, Ritalin LA, and Metadate, as well as Strattera and Provigil. The NICE guidelines for CFS do not advise taking Dexamphetamine or Ritalin. However, a 2007 study found that taking two 10 mg doses of Ritalin each day works much better than placebo at relieving fatigue and concentration problems. More research is needed to study the long-term effects of Ritalin on CFS patients. Because of the difficulties in treating chronic fatigue syndrome, many patients seek alternative therapies. Some, such as acupuncture, yoga, and relaxation techniques, may be helpful and are not dangerous. No scientific evidence exists that vitamin and mineral supplements will relieve CFS, but some people do report that they find supplements helpful. Herbal and Supplements. Popular herbal and dietary supplement remedies for CFS include coenzyme Q10, vitamin B12, vitamin C, magnesium, multivitamins, DHEA, ginseng, and acetylcarnitine. None have been rigorously tested. Some herbs, such as St. John’s wort, ginkgo, and comfrey, may cause serious side effects and drug interactions. Herbal remedies and dietary supplements are not regulated by the FDA. This means that manufacturers and distributors do not need FDA approval to sell their products. In addition, any substance that can affect the body's chemistry can, like any drug, produce side effects that may be harmful. There have been a number of reported cases of serious and even lethal side effects from herbal products. Some so-called natural remedies have been found to contain standard prescription medication. Of specific concern are studies suggesting that up to 30% of herbal patent remedies imported from China have been laced with potent pharmaceuticals, such as phenacetin and steroids. Most reported problems occur in herbal remedies imported from Asia. One study reported that a significant percentage of such remedies contain toxic metals. CFS patients should be wary of any company that promises a cure or urges the purchase of expensive but useless and sometimes potentially dangerous treatments, such as the following:
Of particular note for CFS patients are products containing the ingredient Ma Huang, which contains the stimulants ephedrine and kola nut, a caffeine source. Serious adverse reactions, including seizures, psychosis, and several deaths, have been reported in people taking this supplement for increased energy or weight loss. Products that have only one of these ingredients do not appear to have the same effect, but people should take so-called energy boosting supplements only with the knowledge and recommendation of their doctor. Other alternative remedies with no proven benefit and possible toxic and dangerous side effects include the following:
Resources
ReferencesArmitage R, Landis C, Hoffmann R, Lentz M, Watson NF, Goldberg J, Buchwald D. The impact of a 4-hour sleep delay on slow wave activity in twins discordant for chronic fatigue syndrome. Sleep. 2007;30:657-662. Blockmans D, Persoons P, Van Houdenhove B, Bobbaers H. Does methylphenidate reduce the symptoms of chronic fatigue syndrome? Am J Med. 2006;119:e23-30. Chia J, Chia AY. Chronic fatigue syndrome is associated with chronic enterovirus infection of the stomach. J Clin Pathol. 2008;61:43-48. Goldman L, Ausiello D. Cecil Textbook of Medicine. 23rd ed. Philadelphia, Pa: Saunders Elsevier, 2007. Hampton T. Researchers find genetic clues to chronic fatigue syndrome. JAMA. 2006;295(21):2466-2467. Hickie I, Davenport T, Wakefield D, Vollmer-Conna U, Cameron B, Vernon SD, Reeves WC, Lloyd A; Dubbo Infection Outcomes Study Group. Post-infective and chronic fatigue syndromes preciptated by viral and non-viral pathogens: prospective cohort study. BMJ. 2006;333(7568):575. Epub Sept 1. Jones JF. Orthostatic instability in a population-based study of chronic fatigue syndrome. Am J Med. 2005;118:1415. Kato K, Sullvan PF, Evengard B, Pedersen NL. Premorbid predictors of chronic fatigue. Arch Gen Psychiatry. 2006;63(11):1267-1272. Meeus M, Nijs J. Central sensitization: a biopsychosocial explanation for chronic widespread pain in patients with fibromyalgia and chronic fatigue syndrome. Clin Rheumatol. 2006. Nov 18 (Epub ahead of print). National Institute for Health and Clinical Excellence. Chronic fatigue syndrome/myalgic encephalomyelitis (or encephalopathy): diagnosis and management of CFS/ME in adults and children. August 2007. O'Dowd H, Gladwell P, Rogers CA, Hollinghurst S, Gregory A. Cognitive behavioural therapy in chronic fatigue syndrome: a randomized controlled trial of an outpatient group programme. Health Technol Assess. 2006;10:iii-iv, ix-x, 1-121. Thomas MA, Smith AP. An investigation of the long-term benefits of antidepressant medication in the recovery of patients with chronic fatigue syndrome. Hum Psychopharmacol. 2006;21(8):503-509. Vermeulen RC, Scholte HR. Azithromycin in Chronic Fatigue Syndrome (CFS), an analysis of clinical data. J Transl Med. 2006;4:34.
Review Date:
1/4/2008 Reviewed By: Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc. The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. A licensed medical professional should be consulted for diagnosis and treatment of any and all medical conditions. Call 911 for all medical emergencies. Links to other sites are provided for information only -- they do not constitute endorsements of those other sites. © 1997-
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