Fatigue | |
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Other names | Exhaustion, weariness, tiredness, lethargy, listlessness |
Specialty | Primary care |
Treatment | Avoid known stressors and unhealthy habits (drug use, excessive alcohol consumption, smoking), healthy diet, exercise regularly, medication, hydration, and vitamins |
Fatigue describes a state of tiredness (which is not sleepiness), exhaustion [1] or loss of energy. [2] [3]
In general usage, fatigue often follows prolonged physical or mental activity. When fatigue occurs independently of physical or mental exertion, or does not resolve after rest or sleep, it may have other causes, such as a medical condition. [4]
Fatigue (in the medical sense) is associated with a wide variety of conditions including autoimmune disease, organ failure, chronic pain conditions, mood disorders, heart disease, infectious diseases, and post-infectious-disease states. [5] However fatigue is complex and in up to a third of primary care cases no medical or psychiatric diagnosis is found. [6] [7] [8]
Fatigue (in the general usage sense of normal tiredness) can include both physical and mental fatigue. Physical fatigue results from muscle fatigue brought about by intense physical activity. [9] [10] [11] Mental fatigue results from prolonged periods of cognitive activity which impairs cognitive ability. Mental fatigue can manifest as sleepiness, lethargy, or directed attention fatigue, [12] and can also impair physical performance. [13]
Fatigue in a medical context is used to cover experiences of low energy that are not caused by normal life. [2] [3]
A 2021 review proposed a definition for fatigue as a starting point for discussion: "A multi-dimensional phenomenon in which the biophysiological, cognitive, motivational and emotional state of the body is affected resulting in significant impairment of the individual's ability to function in their normal capacity". [14]
Another definition is that fatigue is "a significant subjective sensation of weariness, increasing sense of effort, mismatch between effort expended and actual performance, or exhaustion independent from medications, chronic pain, physical deconditioning, anaemia, respiratory dysfunction, depression, and sleep disorders". [15]
The use of the term "fatigue" in medical contexts may carry inaccurate connotations from the more general usage of the same word. More accurate terminology may also be needed for variants within the umbrella term of fatigue. [16]
Tiredness which is a normal result of work, mental stress, anxiety, overstimulation and understimulation, jet lag, active recreation, boredom, or lack of sleep is not considered medical fatigue. This is the tiredness described in MeSH Descriptor Data. [17]
Sleepiness refers to a tendency to fall asleep, whereas fatigue refers to an overwhelming sense of tiredness, lack of energy, and a feeling of exhaustion. Sleepiness and fatigue often coexist as a consequence of sleep deprivation. [18] However sleepiness and fatigue may not correlate. [19] Fatigue is generally considered a longer-term condition than sleepiness (somnolence). [20]
Distinguishing features of medical fatigue include
Differentiating characteristics of fatigue that may help identify the possible cause of fatigue include
Some people may have multiple causes of fatigue.
Fatigue can be seen as a uni-dimensional phenomenon that influences different aspects of human life. [37] [38] It can be multi-faceted and broadly defined, making understanding the causes of its manifestations especially difficult in conditions with diverse pathology including autoimmune diseases. [39]
A 2021 review considered that different "types/subsets" of fatigue may exist and that patients normally present with more than one such "type/subset". These different "types/subsets" of fatigue may be different dimensions of the same symptom, and the relative manifestations of each may depend on the relative contribution of different mechanisms. Inflammation may be the root causal mechanism in many cases. [14]
Physical fatigue, or muscle fatigue, is the temporary physical inability of muscles to perform optimally. The onset of muscle fatigue during physical activity is gradual, and depends upon an individual's level of physical fitness – other factors include sleep deprivation and overall health. [40] Physical fatigue can be caused by a lack of energy in the muscle, by a decrease of the efficiency of the neuromuscular junction or by a reduction of the drive originating from the central nervous system, and can be reversed by rest. [41] The central component of fatigue is triggered by an increase of the level of serotonin in the central nervous system. [42] During motor activity, serotonin released in synapses that contact motor neurons promotes muscle contraction. [43] During high level of motor activity, the amount of serotonin released increases and a spillover occurs. Serotonin binds to extrasynaptic receptors located on the axonal initial segment of motor neurons with the result that nerve impulse initiation and thereby muscle contraction are inhibited. [44]
Muscle strength testing can be used to determine the presence of a neuromuscular disease, but cannot determine its cause. Additional testing, such as electromyography, can provide diagnostic information, but information gained from muscle strength testing alone is not enough to diagnose most neuromuscular disorders. [45]
Mental fatigue is a temporary inability to maintain optimal cognitive performance. The onset of mental fatigue during any cognitive activity is gradual, and depends upon an individual's cognitive ability, and also upon other factors, such as sleep deprivation and overall health.
Mental fatigue has also been shown to decrease physical performance. [12] It can manifest as somnolence, lethargy, directed attention fatigue, or disengagement. Research also suggests that mental fatigue is closely linked to the concept of ego depletion, though the validity of the concept is disputed. For example, one pre-registered study of 686 participants found that after exerting mental effort, people are likely to disengage and become less interested in exerting further effort. [46]
Decreased attention can also be described as a more or less decreased level of consciousness. [47] In any case, this can be dangerous when performing tasks that require constant concentration, such as operating large vehicles. For instance, a person who is sufficiently somnolent may experience microsleep. However, objective cognitive testing can be used to differentiate the neurocognitive deficits of brain disease from those attributable to tiredness. [48] [49] [50]
The perception of mental fatigue is believed to be modulated by the brain's reticular activating system (RAS). [51] [52] [53] [54] [55]
Fatigue impacts a driver's reaction time, awareness of hazards around them and their attention. Drowsy drivers are three times more likely to be involved in a car crash, and being awake over 20 hours is the equivalent of driving with a blood-alcohol concentration level of 0.08%. [56]
People with multiple sclerosis experience a form of overwhelming tiredness that can occur at any time of the day, for any duration, and that does not necessarily recur in a recognizable pattern for any given patient, referred to as "neurological fatigue", and often as "multiple sclerosis fatigue" or "lassitude". [57] [58] [59]
People with autoimmune diseases including inflammatory rheumatic diseases such as rheumatoid arthritis, psoriatic arthritis and primary Sjögren's syndrome, experience similar fatigue. [14] [39] Attempts have been made to isolate causes of central nervous system fatigue.
Acute fatigue is that which is temporary and self-limited. Acute fatigue is most often caused by an infection such as the common cold and can be cognized as one part of the sickness behavior response occurring when the immune system fights an infection. [60]
Other common causes of acute fatigue include depression and chemical causes, such as dehydration, poisoning, low blood sugar, or mineral or vitamin deficiencies.
Prolonged fatigue is a self-reported, persistent (constant) fatigue lasting at least one month. [61] [62]
Chronic fatigue is a self-reported fatigue lasting at least 6 consecutive months. Chronic fatigue may be either persistent or relapsing. [63] Chronic fatigue is a symptom of many chronic illnesses and of idiopathic chronic fatigue.[ medical citation needed ]
Fatigue can have significant negative impacts on quality of life. [64] [65] Profound and debilitating fatigue is the most common complaint reported among individuals with autoimmune disease, such as systemic lupus erythematosus, multiple sclerosis, type 1 diabetes, celiac disease, Myalgic Encephalomyelitis/chronic fatigue syndrome, and rheumatoid arthritis. [14]
Fatigue has been described by sufferers as 'incomprehensible' due to its unpredictable occurrence, lack of relationship to physical effort and different character as compared to tiredness. [66]
Fatigue that dissociates by quantum with disease activity represents a large health economic burden and unmet need to patients and to society. [14]
The World Health Organization's ICD-11 classification [67] includes a category MG22 Fatigue (typically fatigue following exertion but sometimes may occur in the absence of such exertion as a symptom of health conditions), and many other categories where fatigue is mentioned as a secondary result of other factors. [68] It does not include any fatigue-based psychiatric illness (unless it is accompanied by related psychiatric symptoms). [69] [70]
DSM-5 lists 'fatigue or loss of energy nearly every day' as one factor in diagnosing depression. [71]
Fatigue is currently measured by many different self-measurement surveys. [72] One example is the Fatigue Severity Scale. [73] [74] [75] There is no consensus on best practice, [76] and the existing surveys do not capture the intermittent nature of some forms of fatigue.
Nintendo announced plans for a device to possibly quantitatively measure fatigue in 2014, [77] but the project was stopped in 2016. [78]
Caffeine and alcohol can cause fatigue. [79] A 2023 Korean study found that alcohol consumption was the variable with the most significant impact on overall fatigue. [80] A 2020 Norway study found that 69% of substance use disorder patients had severe fatigue symptoms. [81]
In up to a third of fatigue primary care cases no medical or psychiatric diagnosis is found. [6] [7] [8] Tiredness is a common medically unexplained symptom. [7]
Fatigue can often be traced to poor sleep habits. [82] Sleep deprivation and disruption is associated with subsequent fatigue. [83] [84] Sleep disturbances due to disease may impact fatigue. [85] [86]
Fatigue may be a side effect of certain medications (e.g., lithium salts, ciprofloxacin); beta blockers, which can induce exercise intolerance, medicines used to treat allergies or coughs [82] ) and many cancer treatments, particularly chemotherapy and radiotherapy.
Adverse life events have been associated with fatigue. [14]
Fatigue is often associated with diseases and conditions. Some major categories of conditions that often list fatigue as a symptom include physical diseases, substance use illness, mental illnesses, and other diseases and conditions.
In some areas it has been proposed that fatigue be separated into primary fatigue, caused directly by a disease process, and ordinary or secondary fatigue, caused by a range of causes including exertion and also secondary impacts on a person of having a disease (such as disrupted sleep). [107] [108] [109] [110] [111] [112] The ICD-11 MG22 definition of fatigue [113] captures both types of fatigue; it includes fatigue that "occur[s] in the absence of... exertion... as a symptom of health conditions."[ medical citation needed ]
Obesity correlates with higher fatigue levels and incidence. [114] [115] [116]
In somatic symptom disorder [117] the patient is overfocused on a physical symptom, such as fatigue, that may or may not be explained by a medical condition. [118] [119] [120]
The concept of adrenal fatigue is often raised in media but no scientific basis has been found for it. [121] [122] [123]
The mechanisms that cause fatigue are not well understood. [39] Several mechanisms may be in operation within a patient, [124] with the relative contribution of each mechanism differing over time. [14]
Some mechanisms proposed as active in fatigue are inflammation, heat shock proteins and reduced brain connectivity.
Inflammation distorts neural chemistry, brain function and functional connectivity across a broad range of brain networks, [125] and has been linked to many types of fatigue. [39] [126] Findings implicate neuroinflammation in the etiology of fatigue in autoimmune and related disorders. [14] [39] Low-grade inflammation may cause an imbalance between energy availability and expenditure. [127]
Cytokines are small protein molecules that modulate immune responses and inflammation (as well as other functions) and may have causal roles in fatigue. [128] [129] However a 2019 review was inconclusive as to whether cytokines play any definitive role in ME/CFS. [130]
The inflammation model may have difficulty in explaining the "unpredictability" and "variability" (i.e. appearing intermittently during the day, and not on all days) of the fatigue associated with inflammatory rheumatic diseases and autoimmune diseases (such as multiple sclerosis). [14]
A small 2016 study found that primary Sjögren's syndrome patients with high fatigue, when compared with those with low fatigue, had significantly higher plasma concentrations of HSP90α, and a tendency to higher concentrations of HSP72. [131] A small 2020 study of Crohn's disease patients found that higher fatigue visual analogue scale (fVAS) scores correlated with hgher HSP90α levels. [132] A related small 2012 trial investigating if application of an IL-1 receptor antagonist (anakinra) would reduce fatigue in primary Sjögren's syndrome patients was inconclusive. [133] [134] [135]
Fatigue has been correlated with reductions in structural and functional connectivity in the brain. [136] This has included in post-stroke, [137] MS, [138] NMOSD and MOG, [15] and ME/CFS. [139] This was also found for fatigue after brain injury, [140] including a significant linear correlation between self-reported fatigue and brain functional connectivity. [141]
Areas of the brain for which there is evidence of relation to fatigue are the thalamus and middle frontal cortex, [141] fronto-parietal and cingulo-opercular, [140] and default mode network, salience network, and thalamocortical loop areas. [136] [142]
Studies have found MS fatigue correlates with damage to NAWM (normal appearing white matter) (which will not show on normal MRI but will show on DTI (diffusion tensor imaging)). [143] [144] [145] [146] [147] [148] Similar functional connectivity alterations related to fatigue may occur in NMOSD and MOG antibody disease. [149]
2023 guidance stated fatigue prevalence is between 4.3% and 21.9%. Prevalence is higher in women than men. [6] [150]
A 2021 German study found that fatigue was the main or secondary reason for 10–20% of all consultations with a primary care physician. [151]
A large study based on the 2004 Health and Retirement Study (HRS), a biennial longitudinal survey of US adults aged 51 and above, with mean age 65, found that 33% of women and 29% of men self-reported fatigue. [152]
This section needs more reliable medical references for verification or relies too heavily on primary sources .(April 2024) |
2023 guidance [6] stated the following:
A 2016 German review found that
A 2014 Australian review recommended that a period of watchful waiting may be appropriate if there are no major warning signs. [154]
A 2009 study found that about 50% of people who had fatigue received a diagnosis that could explain the fatigue after a year with the condition. In those people who had a possible diagnosis, musculoskeletal (19.4%) and psychological problems (16.5%) were the most common. Definitive physical conditions were only found in 8.2% of cases. [155]
Management may include review of existing medications, and other factors and methods explained below.
Medications may be evaluated for side effects that contribute to fatigue [156] [82] [157] [ better source needed ] and the interactions of medications are complex.[ non-primary source needed ] [158]
The UK NICE recommends consideration of amantadine, modafinil and SSRIs for MS fatigue. [159] Psychostimulants such as methylphenidate, amphetamines, and modafinil have been used in the treatment of fatigue related to depression, [160] [161] [162] [163] and medical illness such as chronic fatigue syndrome [164] [165] and cancer. [161] [166] [167] [168] [169] [170] [171] They have also been used to counteract fatigue in sleep loss [172] and in aviation. [173]
Fatigue may be reduced by reducing obesity, caffeine and alcohol intake,[ citation needed ] pain and sleep disturbance, and by improving mental well-being. [177] [14] Aerobic exercise may reduce fatigue. [178] Caffeine is used by many people to manage fatigue, but may have complex effects including later tiredness. [179] [176] [180] [181]
Fatigue in MS has been linked to relatively high endogenous body temperature. [182] [183] [184] [185] [186] [187] [188] [189] [190] [191] [192]
Qigong and Tai chi have been postulated as helpful to reduce fatigue, but the evidence is of low quality. [193] [194] [195]
A small 2022 study found both physical and mental fatigue were significantly reduced after three months of 16:8 intermittent fasting. [196]
A small 2023 study showed possible efficacy of vagus nerve stimulation for fatigue reduction in Sjogren's patients. [129]
Fatigue has been posited as a bio-psycho-physiological state reflecting the body's overall strategy in resource (energy) management. Fatigue may occur when the body wants to limit resource utilisation ("rationing") in order to use resources for healing (part of sickness behaviour) [132] or conserve energy for a particular current or future anticipated need, including a threat. [14]
It has been posited that fatigue had evolutionary benefits in making more of the body's resources available for healing processes, such as immune responses, and in limiting disease spread by tending to reduce social interactions. [124]
Whilst fatigue may vary considerably by person, it may be possible to identify distinguishing characteristics linking it to different causes. [197] [34] [198]
The possible influence of personal psychological factors on fatigue formation is another possible area of research. [199]
Multiple sclerosis (MS) is an autoimmune disease in which the insulating covers of nerve cells in the brain and spinal cord are damaged. This damage disrupts the ability of parts of the nervous system to transmit signals, resulting in a range of signs and symptoms, including physical, mental, and sometimes psychiatric problems. Specific symptoms can include double vision, vision loss, eye pain, muscle weakness, and loss of sensation or coordination. MS takes several forms, with new symptoms either occurring in isolated attacks or building up over time. In the relapsing forms of MS, between attacks, symptoms may disappear completely, although some permanent neurological problems often remain, especially as the disease advances. In the progressive forms of MS, bodily function slowly deteriorates and disability worsens once symptoms manifest and will steadily continue to do so if the disease is left untreated.
Sjögren syndrome or Sjögren's syndrome is a long-term autoimmune disease that affects the body's moisture-producing glands, and often seriously affects other organ systems, such as the lungs, kidneys, and nervous system.
Myalgia is the medical term for muscle pain. Myalgia is a symptom of many diseases. The most common cause of acute myalgia is the overuse of a muscle or group of muscles; another likely cause is viral infection, especially when there has been no trauma.
Fibromyalgia is a medical condition which causes chronic widespread pain, accompanied by fatigue, waking unrefreshed, and cognitive symptoms. Other symptoms include headaches, lower abdominal pain or cramps, and depression. People with fibromyalgia can also experience insomnia and a general hypersensitivity.
Dysautonomia, autonomic failure, or autonomic dysfunction is a condition in which the autonomic nervous system (ANS) does not work properly. This may affect the functioning of the heart, bladder, intestines, sweat glands, pupils, and blood vessels. Dysautonomia has many causes, not all of which may be classified as neuropathic. A number of conditions can feature dysautonomia, such as Parkinson's disease, multiple system atrophy, dementia with Lewy bodies, Ehlers–Danlos syndromes, autoimmune autonomic ganglionopathy and autonomic neuropathy, HIV/AIDS, mitochondrial cytopathy, pure autonomic failure, autism, and postural orthostatic tachycardia syndrome.
Hypersomnia is a neurological disorder of excessive time spent sleeping or excessive sleepiness. It can have many possible causes and can cause distress and problems with functioning. In the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), hypersomnolence, of which there are several subtypes, appears under sleep-wake disorders.
Medically unexplained physical symptoms are symptoms for which a treating physician or other healthcare providers have found no medical cause, or whose cause remains contested. In its strictest sense, the term simply means that the cause for the symptoms is unknown or disputed—there is no scientific consensus. Not all medically unexplained symptoms are influenced by identifiable psychological factors. However, in practice, most physicians and authors who use the term consider that the symptoms most likely arise from psychological causes. Typically, the possibility that MUPS are caused by prescription drugs or other drugs is ignored. It is estimated that between 15% and 30% of all primary care consultations are for medically unexplained symptoms. A large Canadian community survey revealed that the most common medically unexplained symptoms are musculoskeletal pain, ear, nose, and throat symptoms, abdominal pain and gastrointestinal symptoms, fatigue, and dizziness. The term MUPS can also be used to refer to syndromes whose etiology remains contested, including chronic fatigue syndrome, fibromyalgia, multiple chemical sensitivity and Gulf War illness.
A functional symptom is a medical symptom with no known physical cause. In other words, there is no structural or pathologically defined disease to explain the symptom. The use of the term 'functional symptom' does not assume psychogenesis, only that the body is not functioning as expected. Functional symptoms are increasingly viewed within a framework in which 'biological, psychological, interpersonal and healthcare factors' should all be considered to be relevant for determining the aetiology and treatment plans.
Clouding of consciousness, also called brain fog or mental fog, occurs when a person is slightly less wakeful or aware than normal. They are less aware of time and their surroundings, and find it difficult to pay attention. People describe this subjective sensation as their mind being "foggy".
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease that affects the central nervous system (CNS). Several therapies for it exist, although there is no known cure.
Multiple sclerosis can cause a variety of symptoms: changes in sensation (hypoesthesia), muscle weakness, abnormal muscle spasms, or difficulty moving; difficulties with coordination and balance; problems in speech (dysarthria) or swallowing (dysphagia), visual problems, fatigue and acute or chronic pain syndromes, bladder and bowel difficulties, cognitive impairment, or emotional symptomatology. The main clinical measure in progression of the disability and severity of the symptoms is the Expanded Disability Status Scale or EDSS.
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) has a long history with an evolution in medical understanding, diagnoses and social perceptions.
Clinical descriptions of ME/CFS vary. Different groups have produced sets of diagnostic criteria that share many similarities. The biggest differences between criteria are whether post-exertional malaise (PEM) is required, and the number of symptoms needed.
Tumefactive multiple sclerosis is a condition in which the central nervous system of a person has multiple demyelinating lesions with atypical characteristics for those of standard multiple sclerosis (MS). It is called tumefactive as the lesions are "tumor-like" and they mimic tumors clinically, radiologically and sometimes pathologically.
Functional disorders are a group of recognisable medical conditions which are due to changes to the functioning of the systems of the body rather than due to a disease affecting the structure of the body.
Depression, one of the most commonly diagnosed psychiatric disorders, is being diagnosed in increasing numbers in various segments of the population worldwide. Depression in the United States alone affects 17.6 million Americans each year or 1 in 6 people. Depressed patients are at increased risk of type 2 diabetes, cardiovascular disease and suicide. Within the next twenty years depression is expected to become the second leading cause of disability worldwide and the leading cause in high-income nations, including the United States. In approximately 75% of suicides, the individuals had seen a physician within the prior year before their death, 45–66% within the prior month. About a third of those who died by suicide had contact with mental health services in the prior year, a fifth within the preceding month.
Cramp fasciculation syndrome (CFS) is a rare peripheral nerve hyperexcitability disorder. It is more severe than the related disorder known as benign fasciculation syndrome; it causes fasciculations, cramps, pain, fatigue, and muscle stiffness similar to those seen in neuromyotonia. Patients with CFS, like those with neuromyotonia, may also experience paresthesias. Most cases of cramp fasciculation syndrome are idiopathic.
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating long-term medical condition. People with ME/CFS experience delayed worsening of the illness after minor physical or mental activity, which is the hallmark symptom of the illness. Other core symptoms are a greatly reduced ability to do tasks that were previously routine, severe fatigue that does not improve much with rest, and sleep disturbances. Further common symptoms include dizziness or nausea when sitting or standing, along with memory and concentration issues and pain.
The term functional somatic syndrome (FSS) refers to a group of chronic diagnoses with no identifiable organic cause. This term was coined by Hemanth Samkumar. It encompasses disorders such as fibromyalgia, chronic widespread pain, temporomandibular disorder, irritable bowel syndrome, lower back pain, tension headache, atypical face pain, non-cardiac chest pain, insomnia, palpitation, dyspepsia and dizziness. General overlap exists between this term, somatization and somatoform. The status of ME/CFS as a functional somatic syndrome is contested. Although the aetiology remains unclear, there are consistent findings of biological abnormalities, and major health bodies such as the NAM, WHO, and NIH, classify it as an organic disease.
Idiopathic chronic fatigue (ICF) or chronic idiopathic fatigue or insufficient/idiopathic fatigue is a term used for cases of unexplained fatigue that have lasted at least six consecutive months and which do not meet the criteria for Myalgic Encephalomyelitis/chronic fatigue syndrome. Such fatigue is widely understood to have a profound effect on the lives of patients who experience it.
There is no scientific basis for the existence of this disorder and no conclusive method for diagnosis