Fatigue

Fatigue is a state of tiredness (which is not sleepiness), exhaustion<ref name="NHS">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> or loss of energy.<ref name="Mayo-Clinic-Fatigue-2023">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name="Cancer-terms-2023">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> It is a symptom of any of various diseases; it is not a disease in itself.

Fatigue (in the medical sense) is sometimes associated with medical conditions including autoimmune disease, organ failure, chronic pain conditions, mood disorders, heart disease, infectious diseases, and post-infectious-disease states.<ref name="pmid23892338">Template:Cite journal</ref> However, fatigue is complex and in up to a third of primary care cases no medical or psychiatric diagnosis is found.<ref name="BMJ-Best-Practice-2023" /><ref name="Medically unexplained symptoms-2017">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name="pmid31574939">Template:Cite journal</ref>

Fatigue (in the general usage sense of normal tiredness) often follows prolonged physical or mental activity. Physical fatigue results from muscle fatigue brought about by intense physical activity.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> Mental fatigue results from prolonged periods of cognitive activity which impairs cognitive ability, can manifest as sleepiness, lethargy, or directed attention fatigue,<ref name="Marcora 2009 857–864">Template:Cite journal</ref> and can also impair physical performance.<ref name="Martin">Template:Cite journal</ref>

Definition

Fatigue in a medical context is used to cover experiences of low energy that are not caused by normal life.<ref name="Mayo-Clinic-Fatigue-2023"/><ref name="Cancer-terms-2023"/>

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".<ref name="pmid34599320" />

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".<ref name="pmid37180990">Template:Cite journal</ref>

Terminology

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.<ref>Template:Cite journal</ref>

Comparison with other terms

Tiredness

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.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Sleepiness

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.<ref>Template:Cite book</ref> However sleepiness and fatigue may not correlate.<ref>Template:Cite journal</ref> Fatigue is generally considered a longer-term condition than sleepiness (somnolence).<ref name="pmid16376590">Template:Cite journal</ref>

Presentation

Common features

Distinguishing features of medical fatigue include

• unpredictability,
• variability in severity,
• fatigue being relatively profound/overwhelming, and having extensive impact on daily living,
• lack of improvement with rest,
• where an underlying disease is present, the amount of fatigue is often not commensurate with the severity of the underlying disease.<ref name="pmid34599320">Template:Cite journal</ref><ref>Template:Cite journal</ref><ref name=Swain2006>Template:Cite journal</ref><ref>Template:Cite journal</ref>

Differentiating features

Differentiating characteristics of fatigue that may help identify the possible cause of fatigue include

• Post-exertional malaise; a common feature of ME/CFS,<ref>{{#invoke:citation/CS1|citation

|CitationClass=web }}</ref> and experienced by a significant proportion of people with Long Covid,<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> but not a feature of other fatigues.

• Increased by heat or cold; MS fatigue is in many cases affected in this way.<ref name="auto5">{{#invoke:citation/CS1|citation

|CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

• Flare-ups and Remissions; Some fatigue diseases have flareups of a few weeks (lupus<ref>{{#invoke:citation/CS1|citation

|CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>, fibromyalgia<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>). Other fatigue diseases may have longer patterns of activity and remission, or no remissions at all (MS<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name="auto3">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>).

• Variability within a day; Some fatigues (rheumatoid arthritis (RA)<ref name="auto">Template:Cite journal</ref>, cancer-related fatigue<ref>{{#invoke:citation/CS1|citation

|CitationClass=web }}</ref>) seem to often be continual (24/7), whilst others (MS, Sjögren's, lupus, brain injury<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>) often vary in intensity at different times within a day.<ref name="auto"/> A 2010 study found that Sjögren's patients reported fatigue after rising, an improvement in mid-morning, and worsening later in the day, whereas lupus (SLE) patients reported lower fatigue after rising followed by increasing fatigue through the day.<ref name="auto1">Template:Cite journal</ref> ME/CFS symptoms can be continual, or can fluctuate during the day, from day to day, and over longer periods.<ref name="auto3"/> Fibromyalgia fatigue can be continual or variable.<ref>Template:Cite journal</ref>

• The pace of onset may be a related differentiating factor; MS fatigue can have abrupt onset.<ref>{{#invoke:citation/CS1|citation

|CitationClass=web }}</ref>

• Feeling of weight; some fatigues, including that caused by MS, create a sense of weight or gravity; "I feel like I have lead weights attached to my limbs ... or I am being pulled down by gravity."<ref>Template:Cite news</ref>

Some people may have multiple causes of fatigue.

Causes

Fatigue is complex and can be driven and maintained by a potentially wide range of biopsychosocial factors.<ref name="w053">Template:Cite journal</ref> Tiredness is a common medically unexplained symptom.<ref name="Medically unexplained symptoms-2017"/> In up to a third of fatigue primary care cases, no medical or psychiatric diagnosis is found.<ref name="BMJ-Best-Practice-2023" /><ref name="Medically unexplained symptoms-2017"/><ref name="pmid31574939"/>

Adverse life events

Adverse life events have been associated with fatigue.<ref name="pmid34599320"/>

Drug use

A 2021 study in a Korean city found that alcohol consumption was the variable with the most correlation with overall fatigue.<ref>Template:Cite journal</ref> A 2020 Norway study found that 69% of substance use disorder patients had severe fatigue symptoms, and particularly those with extensive use of benzodiazepines.<ref name="auto4">Template:Cite journal</ref> Causality, as opposed to correlation, were not proven in these studies.Template:Citation needed

Sleep disturbance

Fatigue can often be traced to poor sleep habits.<ref name="Mayo-Clinic-Fatigue-Causes-2023"/> Sleep deprivation and disruption is associated with subsequent fatigue.<ref>Template:Cite book</ref><ref>Template:Cite journal</ref> Sleep disturbances due to disease may impact fatigue.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> Caffeine and alcohol can disrupt sleep, causing fatigue.<ref name="Tiredness-and fatigue-2018">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Medications

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,<ref name="Mayo-Clinic-Fatigue-Causes-2023">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> and many cancer treatments, particularly chemotherapy and radiotherapy. Use of benzodiazepines has been found to correlate with higher fatigue.<ref name="auto4"/>

Association with diseases and illnesses

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.Template:Citation needed

Physical diseases

• autoimmune diseases,<ref name="pmid31447842"/> such as celiac disease, lupus, multiple sclerosis, myasthenia gravis, NMOSD, Sjögren's syndrome,<ref name="auto1"/> rheumatoid arthritis,<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref name="pmid34599320" /> spondyloarthropathy and UCTD;<ref>Template:Cite journal</ref> this population's primary concern is fatigue;<ref name="pmid31447842"/><ref>{{#invoke:citation/CS1|citation

|CitationClass=web }}</ref>

• blood disorders, such as anemia and hemochromatosis;<ref name="Cleveland Clinic medical professional 2022 z395">{{#invoke:citation/CS1|citation

|CitationClass=web }}</ref><ref name="Hamilton 2022 g129">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

• brain injury;<ref>{{#invoke:citation/CS1|citation

|CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

• cancer, in which case it is called cancer fatigue;<ref>{{#invoke:citation/CS1|citation

|CitationClass=web }}</ref>

• Covid-19 and long Covid;<ref>{{#invoke:citation/CS1|citation

|CitationClass=web }}</ref>

• developmental disorders such as autism spectrum disorder;<ref name="Williams Gotham p.">Template:Cite journal</ref>
• endocrine diseases or metabolic disorders: diabetes mellitus, hypothyroidism and Addison's disease;<ref name="Friedman">Template:Cite book</ref>
• fibromyalgia;<ref name="Beyond pain">Template:Cite journal</ref>
• heart failure and heart attack;<ref>Template:Cite journal</ref>
• HIV<ref name="Fatigue Symptom Management">Template:Cite journal</ref>
• inborn errors of metabolism such as fructose malabsorption;<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>
• infectious diseases such as infectious mononucleosis or tuberculosis;<ref name=Friedman/>
• irritable bowel syndrome;<ref name="Fatigue in irritable bowel syndrome">Template:Cite journal</ref>
• kidney diseases, e.g., acute renal failure, chronic renal failure;<ref name=Friedman />
• leukemia or lymphoma;Template:Medical citation needed
• liver failure or liver diseases, e.g., hepatitis;<ref name=Friedman/><ref name=Swain2006/>
• Low blood pressure
• Lyme disease;Template:Medical citation needed
• neurological disorders such as narcolepsy, Parkinson's disease, postural orthostatic tachycardia syndrome (POTS) and post-concussion syndrome;Template:Medical citation needed
• nutritional deficiencies, such as, sodium, iron, vitamin B₁₂, and folate deficiencies
• physical trauma and other pain-causing conditions, such as arthritis;Template:Medical citation needed
• sleep deprivation or sleep disorders, e.g. sleep apnea;<ref name=Friedman/>
• strokeTemplate:Medical citation needed
• thyroid disease such as hypothyroidism;Template:Medical citation needed
• sarcoidosis
• mast cell activation syndrome<ref name="PMID33261124">Template:Cite journal</ref><ref name="PMID28262205">Template:Cite journal</ref><ref name="PMID38948000">Template:Cite journal</ref>

Mental illnesses

• anxiety disorders, such as generalized anxiety disorder;<ref name= DSM5>Template:Cite book</ref>
• depression;<ref>{{#invoke:citation/CS1|citation

|CitationClass=web }}</ref><ref name="pmid34599320"/>

• eating disorders, which can produce fatigue due to inadequate nutrition;Template:Medical citation needed

Other

• myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)<ref>Template:Cite journal</ref>
• idiopathic chronic fatigue, a term used to describe chronic fatigue which does not have symptoms of ME/CFS.<ref name="PMC6522773">Template:Cite journal</ref><ref>Template:Cite journal</ref> However ICF does not have a dedicated diagnostic code in the World Health Organization's ICD-11 classification.<ref>{{#invoke:citation/CS1|citation

|CitationClass=web }} This 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.

• 8E49 Postviral fatigue syndrome
• QE84 Acute stress reaction, Combat fatigue
• 6A70-6A7Z Depressive disorders
• 07 Sleep-wake disorders
• FB32.5 Muscle strain or sprain, causing muscular fatigue
• NF01.3 Heat fatigue, transient
• MA82.Y Voice disturbances, causing voice fatigue
• BD1Z Heart failure, unspecified, causing myocardial fatigue
• JA65.Y Conditions predominantly related to pregnancy, causing fatigue which complicates pregnancy
• SD91 Fatigue consumption disorder, causing coughing, fever, diarrhea, chest pain etc.
• MG2A Ageing associated decline in intrinsic capacity, causing senile fatigue
• NF07.2 Exhaustion due to exposure
• NF01 Heat exhaustion
• 6C20 Bodily distress disorder.</ref>
• Gulf War syndrome;<ref>Template:Cite journal</ref>

Primary vs. secondary

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).<ref>Template:Cite news</ref><ref>Template:Cite journal</ref><ref name="Gerber et al 2019">Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>

The ICD-11 MG22 definition of fatigue<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> captures both types of fatigue; it includes fatigue that "occur[s] in the absence of... exertion... as a symptom of health conditions."Template:Medical citation needed

Obesity

Obesity correlates with higher fatigue levels and incidence.<ref>Template:Cite journal</ref><ref name="pmid15851643">Template:Cite journal</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Somatic symptom disorder

In somatic symptom disorder<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> the patient is overfocused on a physical symptom, such as fatigue, that may or may not be explained by a medical condition.<ref>Template:Cite book</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Scientifically unsupported causes

The concept of adrenal fatigue is often raised in media but no scientific basis has been found for it.<ref>Template:Cite journal</ref><ref name="webmd">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>Template:Cite journal</ref>

Mechanisms

The mechanisms that cause fatigue are not well understood.<ref name="pmid31447842"/> Several mechanisms may be in operation within a patient,<ref name="pmid31682277">Template:Cite journal</ref> with the relative contribution of each mechanism differing over time.<ref name="pmid34599320" />

Proposed fatigue explanations due to permanent changes in the brain 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).<ref name="pmid34599320"/>

Inflammation

Inflammation distorts neural chemistry, brain function and functional connectivity across a broad range of brain networks,<ref>Template:Cite journal</ref> and has been linked to many types of fatigue.<ref name="pmid31447842"/><ref>Template:Cite journal</ref> Findings implicate neuroinflammation in the etiology of fatigue in autoimmune and related disorders.<ref name="pmid34599320"/><ref name="pmid31447842"/> Low-grade inflammation may cause an imbalance between energy availability and expenditure.<ref>Template:Cite journal</ref>

Cytokines are small protein molecules that modulate immune responses and inflammation (as well as other functions) and may have causal roles in fatigue.<ref>Template:Cite journal</ref><ref name="Tarn Evans Traianos et al 2023"/> However a 2019 review was inconclusive as to whether cytokines play any definitive role in ME/CFS.<ref>Template:Cite journal</ref>

Reduced brain connectivity

Fatigue has been correlated with reductions in structural and functional connectivity in the brain.<ref name="Qi-2019">Template:Cite journal</ref> This has included in post-stroke,<ref>Template:Cite journal</ref> MS,<ref>Template:Cite journal</ref> NMOSD and MOG,<ref name="pmid37180990"/> and ME/CFS.<ref>Template:Cite journal</ref> This was also found for fatigue after brain injury,<ref name="pmid35221951">Template:Cite journal</ref> including a significant linear correlation between self-reported fatigue and brain functional connectivity.<ref name="pmid26878885">Template:Cite journal</ref>

Areas of the brain for which there is evidence of relation to fatigue are the thalamus and middle frontal cortex,<ref name="pmid26878885" /> fronto-parietal and cingulo-opercular,<ref name="pmid35221951" /> and default mode network, salience network, and thalamocortical loop areas.<ref name="Qi-2019" /><ref>Template:Cite journal</ref>

A 2024 review found that structural connectivity changes may underlie fatigue in pwRRMS but that the overall results were inconclusive, possibly explained by heterogeneity and limited number of studies.<ref>Template:Cite journal</ref>

A small 2023 study found that infratentorial lesion volume (cerebellar and brainstem) was a relatively good predictor of RRMS fatigue severity.<ref>Template:Cite journal</ref>

Damage to brain white matter

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)).<ref>Template:Cite journal</ref><ref name="pmid37180990"/><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> The correlation becomes unreliable in patients aged over 65 due to damage due to ageing.<ref>Template:Cite journal</ref>

Heat shock proteins

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.<ref>Template:Cite journal</ref> A small 2020 study of Crohn's disease patients found that higher fatigue visual analogue scale (fVAS) scores correlated with higher HSP90α levels.<ref name="pmid31601148">Template:Cite journal</ref> 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.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>

Measurement

Fatigue is currently measured by many different self-measurement surveys.<ref>Template:Cite journal</ref> Examples are the Fatigue Symptom Inventory (FSI)<ref>Template:Cite journal</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>Template:Cite journal</ref> and the Fatigue Severity Scale.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>Template:Cite journal</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> There is no consensus on best practice,<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> and the existing surveys do not capture the intermittent nature of some forms of fatigue.

Diagnosis

Diagnosis guidance

A 2023 guidance indicates the following<ref name="BMJ-Best-Practice-2023" />

• in the primary care setting, a medical or psychiatric diagnosis is found in at least two-thirds of patients;
• the most common diagnoses are viral illness, upper respiratory infection, iron-deficiency anaemia, acute bronchitis, adverse effects of a medical agent in the proper dose, and depression or other mental disorder, such as panic disorder, and somatisation disorder;
• the origin of fatigue may be central, brain-derived, or peripheral, usually of a neuromuscular origin—it may be attributed to physical illness, psychological (e.g., psychiatric disorder), social (e.g., family problems), and physiological factors (e.g., old age), occupational illness (e.g., workplace stress);
• when unexplained, clinically evaluated chronic fatigue can be separated into ME/CFS and idiopathic chronic fatigue.<ref name="BMJ-Best-Practice-2023"/>

A 2016 German review found that

• about 20% of people complaining of tiredness to a GP (general practitioner) suffered from a depressive disorder.
• anaemia, malignancies and other serious somatic diseases were only very rarely found in fatigued primary care patients, with prevalence rates hardly differing from non-fatigued patients.
• if fatigue occurred in primary care patients as an isolated symptom without additional abnormalities in the medical history and in the clinical examination, then extensive diagnostic testing rarely helped detect serious diseases. Such testing might also lead to false-positive tests.<ref>Template:Cite journal</ref>

A 2014 Australian review recommended that a period of watchful waiting may be appropriate if there are no major warning signs.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

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.<ref name="pmid19858240">Template:Cite journal</ref>

Classification

By type

Uni- or multi-dimensional

Fatigue can be seen as a uni-dimensional phenomenon that influences different aspects of human life.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> 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.<ref name="pmid31447842">Template:Cite journal</ref>

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.<ref name="pmid34599320" />

Physical

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.<ref name="WebMD">Template:Cite news</ref> 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.<ref>Template:Cite journal</ref> The central component of fatigue is triggered by an increase of the level of serotonin in the central nervous system.<ref name="pmid10919962">Template:Cite journal</ref> During motor activity, serotonin released in synapses that contact motor neurons promotes muscle contraction.<ref>Template:Cite journal</ref> 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.<ref>Template:Cite journal</ref>

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.<ref>Template:Cite journal</ref>

Mental

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.<ref name="Marcora 2009 857–864" /> 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.<ref>Template:Cite journal</ref>

Decreased attention can also be described as a more or less decreased level of consciousness.<ref>Template:Cite book</ref> 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.<ref name="pmid29355911">Template:Cite journal</ref><ref name="pmid30884965">Template:Cite journal</ref><ref name="pmid38079429">Template:Cite journal</ref>

The perception of mental fatigue is believed to be modulated by the brain's reticular activating system (RAS).<ref name="pmid24926625">Template:Cite journal</ref><ref name="pmid28690375">Template:Cite journal</ref><ref name="pmid31216564">Template:Cite journal</ref><ref name="pmid37155119">Template:Cite journal</ref><ref name="pmid31751025">Template:Cite book</ref>

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%.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Neurological fatigue

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".<ref name="pmid32672087">Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> People with autoimmune diseases including inflammatory rheumatic diseases such as rheumatoid arthritis, psoriatic arthritis and primary Sjögren's syndrome, experience similar fatigue.<ref name="pmid34599320"/><ref name="pmid31447842"/> Attempts have been made to isolate causes of central nervous system fatigue.

By timescale

Acute

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.<ref name="Brain, Behavior, and Immunity 2012 pp. 552–558">Template:Cite journal</ref> Other common causes of acute fatigue include depression and chemical causes, such as dehydration, poisoning, low blood sugar, or mineral or vitamin deficiencies.

Prolonged

Prolonged fatigue is a self-reported, persistent (constant) fatigue lasting at least one month.<ref name="pmid34589772">Template:Cite journal</ref><ref name="pmid18458765">Template:Cite journal</ref>

Chronic

Chronic fatigue is a self-reported fatigue lasting at least 6 consecutive months. Chronic fatigue may be either persistent or relapsing.<ref name="CDC1994">Template:Cite journal</ref> Chronic fatigue is a symptom of many chronic illnesses and of idiopathic chronic fatigue.<ref name="mitochondrial content">Template:Cite journal</ref>

By effect

Fatigue can have significant negative impacts on quality of life.<ref>Template:Cite journal</ref> 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.<ref name="pmid34599320" /> 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.<ref>Template:Cite journal</ref>

WHO classification

The World Health Organization's ICD-11 classification<ref name="ICD-11">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> 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.<ref>

• 8E49 Postviral fatigue syndrome
• QE84 Acute stress reaction, Combat fatigue
• 6A70-6A7Z Depressive disorders
• 07 Sleep-wake disorders
• FB32.5 Muscle strain or sprain, causing muscular fatigue
• NF01.3 Heat fatigue, transient
• MA82.Y Voice disturbances, causing voice fatigue
• BD1Z Heart failure, unspecified, causing myocardial fatigue
• JA65.Y Conditions predominantly related to pregnancy, causing fatigue which complicates pregnancy
• SD91 Fatigue consumption disorder, causing coughing, fever, diarrhea, chest pain etc.
• MG2A Ageing associated decline in intrinsic capacity, causing senile fatigue
• NF07.2 Exhaustion due to exposure
• NF01 Heat exhaustion
• 6C20 Bodily distress disorder.

ICD-11</ref> It does not include any fatigue-based psychiatric illness (unless it is accompanied by related psychiatric symptoms).<ref name="Desai2018">Template:Cite journal</ref><ref name="pmid32701520">Template:Cite journal</ref>

DSM-5 lists 'fatigue or loss of energy nearly every day' as one factor in diagnosing depression.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Treatment and management

Management may include review of factors and methods as explained below.

Cessation of medications causing fatigue

Taking of medications with side effects of contributing to fatigue may be ceased.<ref>Template:Cite journal</ref> <ref name="Mayo-Clinic-Fatigue-Causes-2023"/><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>Template:Better source needed<ref>Template:Cite journal</ref>

Medications to treat fatigue

The UK NICE recommends consideration of amantadine, modafinil, and selective serotonin reuptake inhibitors (SSRIs) for MS fatigue.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> A PCORI review, however, found amantadine, methylphenidate, and modafinil no more effective than placebo in reducing fatigue, with side effects reported.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Psychostimulants such as methylphenidate, amphetamines, and modafinil have been used in the treatment of fatigue related to depression,<ref name="pmid18425966">Template:Cite journal</ref><ref name="pmid19281939">Template:Cite journal</ref><ref name="pmid26906078">Template:Cite journal</ref><ref name="pmid34144366">Template:Cite journal</ref> and medical illness such as chronic fatigue syndrome<ref name="pmid20088743">Template:Cite journal</ref><ref name="pmid18505357">Template:Cite journal</ref> and cancer.<ref name="pmid19281939" /><ref name="pmid8856815">Template:Cite journal</ref><ref name="pmid20870637">Template:Cite journal</ref><ref name="pmid21251796">Template:Cite journal</ref><ref name="pmid24416225">Template:Cite journal</ref><ref name="pmid25299141">Template:Cite journal</ref><ref name="pmid25814977">Template:Cite journal</ref> They have also been used to counteract fatigue in sleep loss<ref name="pmid16268386">Template:Cite journal</ref> and in aviation.<ref name="pmid33754977">Template:Cite journal</ref>

Mental health tools

CBT can be useful for fatigue,<ref>Template:Cite journal</ref><ref name="auto2">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> including ME/CFS<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> but is not included in NICE guidelines for ME/CFS treatment.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Other approaches

Avoidance of body heat

Fatigue in MS often correlates with relatively high endogenous body temperature.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name="auto5"/><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref name="pmid35963205">Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite book</ref>Template:Excessive citations inline

Improved sleep

Improving sleep has been associated with reduced fatigue but only in small studies.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref name="auto2"/>

Intermittent fasting

A very small 2022 study found 40% reductions in fatigue categorisations after three months of 16:8 intermittent fasting.<ref>Template:Cite journal</ref>

Vagus nerve stimulation

A very small 2023 study of Sjogren's patients showed reductions in self-reported fatigue after 56 days of vagus nerve stimulation.<ref name="Tarn Evans Traianos et al 2023">Template:Cite journal</ref>

Qigong and Tai Chi

Qigong and Tai chi have been postulated as helpful to reduce fatigue, but the evidence is of low quality.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite book</ref>

Approaches to managing fatigue

Some health systems help people manage their fatigue better through attitude changes and skills transference.<ref name="auto2"/><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Prevalence

2023 guidance stated fatigue prevalence is between 4.3% and 21.9%. Prevalence is higher in women than men.<ref name="BMJ-Best-Practice-2023">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>Template:Cite journal</ref>

A 2021 German study found that fatigue was the main or secondary reason for 10–20% of all consultations with a primary care physician.<ref>Template:Cite journal</ref>

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.<ref>Template:Cite journal</ref>

Fatigue represents a large health economic burden and unmet need to patients and to society.<ref name="pmid34599320" />

Possible purposes of fatigue

Body resource management purposes

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)<ref name="pmid31601148"/> or conserve energy for a particular current or future anticipated need, including a threat.<ref name="pmid34599320"/>

Evolutionary purposes

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.<ref name="pmid31682277"/>

See also

• Acquiescence
• Affect
• Cancer-related fatigue
• Central governor
• Chronic stress
• Clouding of consciousness
• Combat stress reaction
• Directed attention fatigue
• Disorders of diminished motivation
• Effects of fatigue on safety
• Feeling
• Gaucher's disease
• Heat illness
• Malaise
• Microsleep
• Museum fatigue
• Presenteeism
• Sleep-deprived driving
• Pacing (activity management)
• Zoom fatigue

Further reading

• Byung-Chul Han: Müdigkeitsgesellschaft. Matthes & Seitz, Berlin 2010, Template:ISBN. (Philosophical essay about fatigue as a sociological problem and symptom).
  • Danish edition: Træthedssamfundet. Møller, 2012, Template:ISBN.
  • Dutch edition: De vermoeide samenleving. van gennep, 2012, Template:ISBN.
  • Italian editions: La società della stanchezza. nottetempo, 2012, Template:ISBN.
  • Korean edition: 한병철 지음 | 김태환 옮김. Moonji, 2011, Template:ISBN.
  • Spanish edition: La sociedad del cansancio. Herder Editorial, 2012, Template:ISBN.
  • South, David (1993). Professor puts chronic fatigue into historical perspective. Hannah Institute for the History of Medicine Number 18 Summer 1993, p. 1

External links

• Fatigue – Information for Patients, U.S. National Cancer Institute