View source for Fatigue

{{Short description|State of tiredness, exhaustion or loss of energy}}
{{About|the medical term|other uses|Fatigue (disambiguation)}}
{{Distinguish|Muscle weakness|Lethargy}}
{{cs1 config|name-list-style=vanc}}
{{Infobox medical condition
| name = Fatigue
| synonyms = Exhaustion, weariness, tiredness, lethargy, listlessness
| image = Cfs_woman_sketch.jpg
| caption = Artistic representation of [[ME/CFS]]
| treatment = Avoid known stressors and unhealthy habits ([[Substance abuse|drug use]], [[excessive alcohol consumption]], smoking), healthy diet, exercise regularly, [[medication]], [[Drinking|hydration]], and [[vitamins]]
}}

'''Fatigue''' is a state of being without energy for a prolonged period of time.<ref name="Mayo-Clinic-Fatigue-2023">{{cite web |url=https://www.mayoclinic.org/symptoms/fatigue/basics/definition/sym-20050894 | title=Fatigue | website=[[Mayo Clinic]] | access-date=2023-01-06 | archive-date=2023-01-06 | archive-url=https://web.archive.org/web/20230106193733/https://www.mayoclinic.org/symptoms/fatigue/basics/definition/sym-20050894 | url-status=live }}</ref><ref name="Cancer-terms-2023">{{Cite web |url=https://www.cancer.gov/publications/dictionaries/cancer-terms/def/fatigue#:~:text=(fuh%2DTEEG),may%20be%20acute%20or%20chronic |title=Cancer terms |access-date=2023-01-06 |archive-date=2023-01-06 |archive-url=https://web.archive.org/web/20230106193733/https://www.cancer.gov/publications/dictionaries/cancer-terms/def/fatigue#:~:text=(fuh%2DTEEG),may%20be%20acute%20or%20chronic |url-status=live }}</ref> Fatigue is used in two contexts: in the medical sense, and in the sense of normal tiredness.

In the medical sense, fatigue is seen as a symptom, and is sometimes associated with medical conditions including [[autoimmune disease]], [[organ failure]], [[chronic pain]] conditions, [[mood disorder]]s, [[heart disease]], [[infectious disease]]s, and post-infectious-disease states.<ref name="pmid23892338">{{cite journal |vauthors=Finsterer J, Mahjoub SZ |title=Fatigue in healthy and diseased individuals |journal=Am J Hosp Palliat Care |volume=31 |issue=5 |pages=562–575 |date=August 2014 |pmid=23892338 |doi=10.1177/1049909113494748 |s2cid=12582944 |url=}}</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">{{cite web |url=https://www.nhs.uk/conditions/medically-unexplained-symptoms/ | title=Medically unexplained symptoms | date=19 October 2017 | access-date=6 January 2023 | archive-date=29 September 2017 | archive-url=https://web.archive.org/web/20170929113241/http://www.nhs.uk/conditions/medically-unexplained-symptoms/Pages/Somatisation.aspx | url-status=live }}</ref><ref name="pmid31574939">{{cite journal |vauthors=Haß U, Herpich C, Norman K |title=Anti-Inflammatory Diets and Fatigue |journal=Nutrients |volume=11 |issue=10 |date=September 2019 |page=2315 |pmid=31574939 |pmc=6835556 |doi=10.3390/nu11102315 |url=|doi-access=free }}</ref>

In the sense of tiredness, fatigue often follows prolonged physical or mental activity. Physical fatigue results from [[muscle fatigue]] brought about by intense [[physical activity]].<ref>{{cite journal | vauthors = Gandevia SC | title = Some central and peripheral factors affecting human motoneuronal output in neuromuscular fatigue | journal = Sports Medicine | volume = 13 | issue = 2 | pages = 93–98 | date = February 1992 | pmid = 1561512 | doi = 10.2165/00007256-199213020-00004 | s2cid = 20473830 }}</ref><ref>{{cite journal | vauthors = Hagberg M | title = Muscular endurance and surface electromyogram in isometric and dynamic exercise | journal = Journal of Applied Physiology | volume = 51 | issue = 1 | pages = 1–7 | date = July 1981 | pmid = 7263402 | doi = 10.1152/jappl.1981.51.1.1 }}</ref><ref>{{cite journal | vauthors = Hawley JA, Reilly T | title = Fatigue revisited | journal = Journal of Sports Sciences | volume = 15 | issue = 3 | pages = 245–246 | date = June 1997 | pmid = 9232549 | doi = 10.1080/026404197367245 }}</ref> Mental fatigue results from prolonged periods of [[Cognition|cognitive]] activity which impairs cognitive ability, can manifest as [[sleepiness]], [[lethargy]], or [[directed attention fatigue]],<ref name="Marcora 2009 857–864">{{cite journal | vauthors = Marcora SM, Staiano W, Manning V | title = Mental fatigue impairs physical performance in humans | journal = Journal of Applied Physiology | volume = 106 | issue = 3 | pages = 857–864 | date = March 2009 | pmid = 19131473 | doi = 10.1152/japplphysiol.91324.2008 | citeseerx = 10.1.1.557.3566 | s2cid = 12221961 }}</ref> and can also impair physical performance.<ref name="Martin">{{cite journal |vauthors=Martin K, Meeusen R, Thompson KG, Keegan R, Rattray B |title=Mental Fatigue Impairs Endurance Performance: A Physiological Explanation |journal=Sports Med |volume=48 |issue=9 |pages=2041–2051 |date=September 2018 |pmid=29923147 |doi=10.1007/s40279-018-0946-9 |s2cid=49317682 |url=}}</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, [[Anemia|anaemia]], respiratory dysfunction, [[Depression (mood)|depression]], and sleep disorders"''.<ref name="pmid37180990">{{cite journal |last1=Camera |first1=Valentina |last2=Mariano |first2=Romina |last3=Messina |first3=Silvia |last4=Menke |first4=Ricarda |last5=Griffanti |first5=Ludovica |last6=Craner |first6=Matthew |last7=Leite |first7=Maria I |last8=Calabrese |first8=Massimiliano |last9=Meletti |first9=Stefano |last10=Geraldes |first10=Ruth |last11=Palace |first11=Jacqueline A |title=Shared imaging markers of fatigue across multiple sclerosis, aquaporin-4 antibody neuromyelitis optica spectrum disorder and MOG antibody disease |journal=Brain Communications |date=2 May 2023 |volume=5 |issue=3 |article-number=fcad107 |doi=10.1093/braincomms/fcad107 |pmid=37180990 |pmc=10171455 }}</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>{{cite journal | pmc=8142120 | year=2020 | last1=Hubbard | first1=A. L. | last2=Golla | first2=H. | last3=Lausberg | first3=H. | title=What's in a name? That which we call Multiple Sclerosis Fatigue | journal=Multiple Sclerosis | volume=27 | issue=7 | pages=983–988 | doi=10.1177/1352458520941481 | pmid=32672087 }}</ref>

===Comparison with other terms===
====Tiredness====
Tiredness which is a normal result of [[Work (human activity)|work]], mental [[Stress (medicine)|stress]], [[anxiety]], overstimulation and understimulation, [[jet lag]], active [[recreation]], [[boredom]], or [[Sleep deprivation|lack of sleep]] is not considered medical fatigue. This is the tiredness described in MeSH Descriptor Data.<ref>{{Cite web|url=https://meshb.nlm.nih.gov/record/ui?ui=D005221|title=MeSH Browser|website=meshb.nlm.nih.gov|access-date=2024-01-25|archive-date=2023-05-08|archive-url=https://web.archive.org/web/20230508182945/https://meshb.nlm.nih.gov/record/ui?ui=D005221|url-status=live}}</ref>

====Exhaustion====
Exhaustion is a state of extreme tiredness.<ref>{{cite web | title=Exhaustion | url=https://dictionary.cambridge.org/dictionary/english/exhaustion }}</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>{{Cite book|url=https://www.ncbi.nlm.nih.gov/books/NBK2645/|title=Patient Safety and Quality: An Evidence-Based Handbook for Nurses|first=Ann E.|last=Rogers|chapter=The Effects of Fatigue and Sleepiness on Nurse Performance and Patient Safety|series=Advances in Patient Safety|editor-first=Ronda G.|editor-last=Hughes|date=April 11, 2008|publisher=Agency for Healthcare Research and Quality (US)|via=PubMed|pmid=21328747|access-date=April 11, 2024|archive-date=April 19, 2024|archive-url=https://web.archive.org/web/20240419212000/https://ncbi.nlm.nih.gov/books/NBK2645/|url-status=live}}</ref> However sleepiness and fatigue may not correlate.<ref>{{Cite journal|title=Fatigue and sleep disorders|first1=K. L.|last1=Lichstein|first2=M. K.|last2=Means|first3=S. L.|last3=Noe|first4=R. N.|last4=Aguillard|date=August 11, 1997|journal=Behaviour Research and Therapy|volume=35|issue=8|pages=733–740|doi=10.1016/s0005-7967(97)00029-6|pmid=9256516}}</ref> Fatigue is generally considered a longer-term condition than sleepiness (somnolence).<ref name="pmid16376590">{{cite journal | vauthors = Shen J, Barbera J, Shapiro CM | title = Distinguishing sleepiness and fatigue: focus on definition and measurement | journal = Sleep Medicine Reviews | volume = 10 | issue = 1 | pages = 63–76 | date = February 2006 | pmid = 16376590 | doi = 10.1016/j.smrv.2005.05.004 }}</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">{{cite journal |last1=Davies |first1=Kristen |last2=Dures |first2=Emma |last3=Ng |first3=Wan-Fai |title=Fatigue in inflammatory rheumatic diseases: current knowledge and areas for future research |journal=Nature Reviews Rheumatology |date=November 2021 |volume=17 |issue=11 |pages=651–664 |doi=10.1038/s41584-021-00692-1 |pmid=34599320 |s2cid=238233411 |url=https://eprints.ncl.ac.uk/277695 |archive-date=2023-12-09 |access-date=2023-12-20 |archive-url=https://web.archive.org/web/20231209191903/https://eprints.ncl.ac.uk/277695 |url-status=live }}</ref><ref>{{cite journal |last1=Goërtz |first1=Yvonne M. J. |last2=Braamse |first2=Annemarie M. J. |last3=Spruit |first3=Martijn A. |last4=Janssen |first4=Daisy J. A. |last5=Ebadi |first5=Zjala |last6=Van Herck |first6=Maarten |last7=Burtin |first7=Chris |last8=Peters |first8=Jeannette B. |last9=Sprangers |first9=Mirjam A. G. |last10=Lamers |first10=Femke |last11=Twisk |first11=Jos W. R. |last12=Thong |first12=Melissa S. Y. |last13=Vercoulen |first13=Jan H. |last14=Geerlings |first14=Suzanne E. |last15=Vaes |first15=Anouk W. |last16=Beijers |first16=Rosanne J. H. C. G. |last17=van Beers |first17=Martijn |last18=Schols |first18=Annemie M. W. J. |last19=Rosmalen |first19=Judith G. M. |last20=Knoop |first20=Hans |title=Fatigue in patients with chronic disease: results from the population-based Lifelines Cohort Study |journal=Scientific Reports |date=25 October 2021 |volume=11 |issue=1 |page=20977 |doi=10.1038/s41598-021-00337-z |pmid=34697347 |pmc=8546086 |bibcode=2021NatSR..1120977G }}</ref><ref name=Swain2006>{{cite journal |last1=Swain |first1=Mark G |title=Fatigue in Liver Disease: Pathophysiology and Clinical Management |journal=Canadian Journal of Gastroenterology |date=2006 |volume=20 |issue=3 |pages=181–188 |doi=10.1155/2006/624832 |doi-access=free |pmid=16550262 |pmc=2582971 }}</ref><ref>{{cite journal |last1=Pope |first1=Janet E |title=Management of Fatigue in Rheumatoid Arthritis |journal=RMD Open |date=May 2020 |volume=6 |issue=1 |article-number=e001084 |doi=10.1136/rmdopen-2019-001084 |pmid=32385141 |pmc=7299512 }}</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>{{Cite web |url=https://www.iqwig.de/download/n21-01_me-cfs-aktueller-kenntnisstand_abschlussbericht_v1-0.pdf |title=Myalgische Enzephalomyelitis / Chronic Fatigue Syndrome (ME/CFS)&nbsp;– Aktueller Kenntnisstand |access-date=2024-03-26 |archive-date=2023-11-02 |archive-url=https://web.archive.org/web/20231102160213/https://www.iqwig.de/download/n21-01_me-cfs-aktueller-kenntnisstand_abschlussbericht_v1-0.pdf |url-status=live }}</ref> and experienced by a significant proportion of people with [[Long Covid]],<ref>{{Cite web|url=https://meassociation.org.uk/2024/04/neurology-today-are-me-cfs-and-long-covid-part-of-the-same-disorder/|title=Neurology Today: Are ME/CFS and Long Covid part of the same disorder?|first=Russell|last=Fleming|date=April 19, 2024|website=The ME Association|access-date=April 23, 2024|archive-date=May 10, 2024|archive-url=https://web.archive.org/web/20240510141605/https://meassociation.org.uk/2024/04/neurology-today-are-me-cfs-and-long-covid-part-of-the-same-disorder/|url-status=live}}</ref> but not a feature of other fatigues.
* Increased by heat or cold; [[Signs and symptoms of multiple sclerosis#Fatigue|MS fatigue]] is in many cases affected in this way.<ref name="auto5">{{Cite web|url=https://mstrust.org.uk/a-z/temperature-sensitivity|title=Temperature sensitivity &#124; MS Trust|first=M. S.|last=Trust|website=mstrust.org.uk|access-date=2024-03-15|archive-date=2024-01-17|archive-url=https://web.archive.org/web/20240117003924/https://mstrust.org.uk/a-z/temperature-sensitivity|url-status=live}}</ref><ref>{{Cite web|url=https://www.msaustralia.org.au/news/ms-and-heat-fatigue/|title=MS and heat fatigue: does it come down to sweating?|access-date=2024-04-08|archive-date=2024-04-08|archive-url=https://web.archive.org/web/20240408134404/https://www.msaustralia.org.au/news/ms-and-heat-fatigue/|url-status=live}}</ref>
* Flare-ups and Remissions; Some fatigue diseases have flareups of a few weeks ([[lupus]],<ref>{{Cite web|url=https://www.nhs.uk/conditions/lupus/|title=Lupus|date=October 24, 2017|website=nhs.uk}}</ref><ref>{{Cite web|url=https://lupusuk.org.uk/manage-your-lupus/|title=Manage Your Lupus &#124; Lupus UK|website=lupusuk.org.uk}}</ref> [[fibromyalgia]]<ref>{{Cite web|url=https://my.clevelandclinic.org/health/diseases/4832-fibromyalgia|title=Fibromyalgia: Symptoms, Diagnosis & Treatment|website=Cleveland Clinic}}</ref>). Other fatigue diseases may have longer patterns of activity and remission, or no remissions at all (MS<ref>{{Cite web|url=https://practicalneurology.com/articles/2018-july-aug/fatigue-in-patients-with-multiple-sclerosis|title=Fatigue in Patients With Multiple Sclerosis|website=Practical Neurology|access-date=2021-10-18|archive-date=2022-06-16|archive-url=https://web.archive.org/web/20220616230104/https://practicalneurology.com/articles/2018-july-aug/fatigue-in-patients-with-multiple-sclerosis|url-status=live}}</ref><ref>{{cite web |url=https://www.mssociety.org.uk/about-ms/types-of-ms/relapsing-remitting-ms |title=Relapsing remitting MS (RRMS) |publisher=MS Society |archive-url=https://web.archive.org/web/20240408133719/https://www.mssociety.org.uk/about-ms/types-of-ms/relapsing-remitting-ms |archive-date=2024-04-08}}</ref><ref name="auto3">{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/index.html|title=Presentation and Clinical Course of ME/CFS &#124; Information for Healthcare Providers &#124; Myalgic Encephalomyelitis/Chronic Fatigue Syndrome ME/CFS &#124; CDC|date=November 19, 2019|website=www.cdc.gov|access-date=April 11, 2024|archive-date=July 28, 2020|archive-url=https://web.archive.org/web/20200728125126/https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/index.html|url-status=live}}</ref>).
* Variability within a day; Some fatigues ([[Rheumatoid arthritis|rheumatoid arthritis (RA)]],<ref name="auto">{{cite journal |last1=Jaime-Lara |first1=Rosario B. |last2=Koons |first2=Brittany C. |last3=Matura |first3=Lea Ann |last4=Hodgson |first4=Nancy A. |last5=Riegel |first5=Barbara |title=A Qualitative Metasynthesis of the Experience of Fatigue Across Five Chronic Conditions |journal=Journal of Pain and Symptom Management |date=June 2020 |volume=59 |issue=6 |pages=1320–1343 |doi=10.1016/j.jpainsymman.2019.12.358 |pmid=31866485 |pmc=7239763 }}</ref> [[cancer-related fatigue]]<ref>{{Cite web|url=https://www.cancerresearchuk.org/about-cancer/coping/physically/fatigue/what-is-cancer-fatigue|title=What is cancer fatigue?|website=www.cancerresearchuk.org|access-date=2023-01-06|archive-date=2023-01-06|archive-url=https://web.archive.org/web/20230106185829/https://www.cancerresearchuk.org/about-cancer/coping/physically/fatigue/what-is-cancer-fatigue|url-status=live}}</ref>) seem to often be continual (24/7), whilst others (MS, Sjögren's, lupus, brain injury<ref>{{Cite web|url=https://www.brainline.org/article/fatigue-after-brain-injury-brainline-talks-dr-nathan-zasler|title=Fatigue After Brain Injury: BrainLine Talks With Dr. Nathan Zasler &#124; BrainLine|date=February 4, 2010|website=www.brainline.org|access-date=April 8, 2024|archive-date=April 8, 2024|archive-url=https://web.archive.org/web/20240408132546/https://www.brainline.org/article/fatigue-after-brain-injury-brainline-talks-dr-nathan-zasler|url-status=live}}</ref><ref>{{cite web | url=https://www.bbc.com/future/article/20160817-the-daily-struggle-of-living-with-extreme-fatigue | title=The daily struggle of living with extreme fatigue | date=18 August 2016 | access-date=30 March 2024 | archive-date=30 March 2024 | archive-url=https://web.archive.org/web/20240330103010/https://www.bbc.com/future/article/20160817-the-daily-struggle-of-living-with-extreme-fatigue | url-status=live }}</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">{{cite journal |last1=Ng |first1=W. F. |last2=Bowman |first2=S. J. |title=Primary Sjogren's syndrome: too dry and too tired |journal=Rheumatology |date=May 2010 |volume=49 |issue=5 |pages=844–853 |doi=10.1093/rheumatology/keq009 |pmid=20147445 }}</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>{{Cite journal|title=Pain and Fatigue Variability Patterns Distinguish Subgroups of Fibromyalgia Patients|first1=Emily J.|last1=Bartley|first2=Michael E.|last2=Robinson|first3=Roland|last3=Staud|date=April 20, 2018|journal=The Journal of Pain|volume=19|issue=4|pages=372–381|doi=10.1016/j.jpain.2017.11.014|pmid=29253551|pmc=5869098}}</ref>
* The pace of onset may be a related differentiating factor; MS fatigue can have abrupt onset.<ref>{{cite web |url=https://mstrust.org.uk/a-z/fatigue |title=Fatigue &#124; MS Trust |access-date=2024-04-08 |archive-date=2024-01-16 |archive-url=https://web.archive.org/web/20240116234819/https://mstrust.org.uk/a-z/fatigue |url-status=live }}</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>{{cite news | url=https://www.abc.net.au/news/2023-09-09/why-mecfs-is-nothing-like-everyday-fatigue/102776070 | title=Dee feels like a prisoner in her own body and wants more people to know the truth about her illness | newspaper=ABC News | date=8 September 2023 | archive-date=2024-06-10 | access-date=2024-06-10 | archive-url=https://web.archive.org/web/20240610130332/https://www.abc.net.au/news/2023-09-09/why-mecfs-is-nothing-like-everyday-fatigue/102776070 | url-status=live }}</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 model|biopsychosocial factors]].<ref name="w053">{{cite journal | last=Dures | first=Emma | title=2023 EULAR recommendations for the management of fatigue in people with inflammatory rheumatic and musculoskeletal diseases | journal=Annals of the Rheumatic Diseases | publisher=Elsevier BV | volume=83 | issue=10 | year=2024 | issn=0003-4967 | doi=10.1136/ard-2023-224514 | doi-access=free | pages=1260–1267 | pmid=38050029 | url=https://ard.bmj.com/content/annrheumdis/early/2023/11/22/ard-2023-224514.full.pdf | access-date=2025-03-18 | archive-date=2023-12-08 | archive-url=https://web.archive.org/web/20231208184637/https://ard.bmj.com/content/annrheumdis/early/2023/11/22/ard-2023-224514.full.pdf | url-status=live }}</ref> Tiredness is a common [[Medically unexplained physical symptoms|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>{{cite journal |last1=Kim |first1=Kyeha |last2=Oh |first2=Jihyun |title=Factors affecting physical and mental fatigue in adults from South Korea: A cross-sectional study |journal=Medicine |date=15 December 2023 |volume=102 |issue=50 |article-number=e36549 |doi=10.1097/MD.0000000000036549 |pmid=38115348 |pmc=10727629 }}</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">{{Cite journal|title=Impact of clinical and sociodemographic factors on fatigue among patients with substance use disorder: a cohort study from Norway for the period 2016–2020 - PMC|date=2020 |pmc=7737389 |journal=Substance Abuse Treatment, Prevention, and Policy |volume=15 |article-number=93 |doi=10.1186/s13011-020-00334-x |doi-access=free |pmid=33317568 | vauthors = Vold JH, Gjestad R, Aas CF, Chalabianloo F, Skurtveit S, Løberg EM, Johansson KA, Fadnes LT |issue=1 }}</ref> Causality, as opposed to correlation, were not proven in these studies.{{citation needed|date=May 2024}}

===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>{{cite book |title=Commercial Motor Vehicle Driver Fatigue, Long-Term Health, and Highway Safety: Research Needs |date=12 August 2016 |publisher=National Academies Press (US) |chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK384963/ |chapter=Consequences of Fatigue from Insufficient Sleep |access-date=25 February 2024 |archive-date=24 May 2022 |archive-url=https://web.archive.org/web/20220524064500/https://www.ncbi.nlm.nih.gov/books/NBK384963/ |url-status=live }}</ref><ref>{{Cite journal|title=Predicting and mitigating fatigue effects due to sleep deprivation: A review|first1=Kylie C.|last1=Kayser|first2=Vannia A.|last2=Puig|first3=Justin R.|last3=Estepp|date=February 25, 2022|journal=Frontiers in Neuroscience|volume=16|article-number=930280 |doi=10.3389/fnins.2022.930280|doi-access=free |pmid=35992930 |pmc=9389006 }}</ref> Sleep disturbances due to disease may impact fatigue.<ref>{{cite journal |last1=Strober |first1=Lauren B. |title=Fatigue in Multiple Sclerosis: A Look at the Role of Poor Sleep |journal=Frontiers in Neurology |date=12 February 2015 |volume=6 |page=21 |doi=10.3389/fneur.2015.00021 |doi-access=free |pmid=25729378 |pmc=4325921 }}</ref><ref>{{cite journal |last1=GudbjöRnsson |first1=B. |last2=Broman |first2=J. E. |last3=Hetta |first3=J. |last4=HäLlgren |first4=R. |title=SLEEP DISTURBANCES IN PATIENTS WITH PRIMARY SJÖGREN'S SYNDROME |journal=Rheumatology |date=1993 |volume=32 |issue=12 |pages=1072–1076 |doi=10.1093/rheumatology/32.12.1072 |pmid=8252317 }}</ref> Caffeine and alcohol can disrupt sleep, causing fatigue.<ref name="Tiredness-and fatigue-2018">{{cite web |url=https://111.wales.nhs.uk/Tirednessandfatigue/ | title=Tiredness and fatigue | date=26 April 2018 | access-date=6 January 2023 | archive-date=6 January 2023 | archive-url=https://web.archive.org/web/20230106173824/https://111.wales.nhs.uk/Tirednessandfatigue/ | url-status=live }}</ref>

===Medications===
Fatigue may be a side effect of certain [[medication]]s (e.g., [[lithium salt]]s, [[ciprofloxacin]]); [[beta blocker]]s, which can induce [[exercise intolerance]], medicines used to treat allergies or coughs,<ref name="Mayo-Clinic-Fatigue-Causes-2023">{{Cite web|url=https://www.mayoclinic.org/symptoms/fatigue/basics/definition/sym-20050894|title=Fatigue Causes|website=Mayo Clinic|access-date=2023-01-06|archive-date=2023-01-06|archive-url=https://web.archive.org/web/20230106193733/https://www.mayoclinic.org/symptoms/fatigue/basics/definition/sym-20050894|url-status=live}}</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.{{citation needed|date=May 2024}}

====Physical diseases====

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* [[autoimmune disease]]s,<ref name="pmid31447842"/> such as [[celiac disease]], [[lupus]], [[Signs and symptoms of multiple sclerosis#fatigue|multiple sclerosis]], [[myasthenia gravis]], [[NMOSD]], [[Sjögren's syndrome]],<ref name="auto1"/> [[rheumatoid arthritis]],<ref>{{cite journal |last1=van Hoogmoed |first1=D. |last2=Fransen |first2=J. |last3=Bleijenberg |first3=G. |last4=van Riel |first4=P. |title=Physical and psychosocial correlates of severe fatigue in rheumatoid arthritis |journal=Rheumatology |date=July 2010 |volume=49 |issue=7 |pages=1294–1302 |doi=10.1093/rheumatology/keq043 |pmid=20353956 }}</ref><ref>{{Cite journal|title=Fatigue in Systemic Lupus Erythematosus and Rheumatoid Arthritis: A Comparison of Mechanisms, Measures and Management|first1=Mrinalini|last1=Dey|first2=Ioannis|last2=Parodis|first3=Elena|last3=Nikiphorou|date=January 26, 2021|journal=Journal of Clinical Medicine|volume=10|issue=16|page=3566|doi=10.3390/jcm10163566|doi-access=free |pmid=34441861 |pmc=8396818 }}</ref><ref>{{cite journal |last1=Geenen |first1=Rinie |last2=Dures |first2=Emma |title=A biopsychosocial network model of fatigue in rheumatoid arthritis: a systematic review |journal=Rheumatology |date=November 2019 |volume=58 |issue=Supplement_5 |pages=v10–v21 |doi=10.1093/rheumatology/kez403 |pmid=31682275 |pmc=6827269 }}</ref><ref name="pmid34599320" /> [[spondyloarthropathy]] and [[UCTD]];<ref>{{cite journal |last1=Hafiz |first1=Waleed |last2=Nori |first2=Rawad |last3=Bregasi |first3=Ariana |last4=Noamani |first4=Babak |last5=Bonilla |first5=Dennisse |last6=Lisnevskaia |first6=Larissa |last7=Silverman |first7=Earl |last8=Bookman |first8=Arthur A. M. |last9=Johnson |first9=Sindhu R. |last10=Landolt-Marticorena |first10=Carolina |last11=Wither |first11=Joan |title=Fatigue severity in anti-nuclear antibody-positive individuals does not correlate with pro-inflammatory cytokine levels or predict imminent progression to symptomatic disease |journal=Arthritis Research & Therapy |date=2019 |volume=21 |issue=1 |page=223 |doi=10.1186/s13075-019-2013-9 |pmid=31685018 |pmc=6827224 |doi-access=free }}</ref> this population's primary concern is fatigue;<ref name="pmid31447842"/><ref>{{cite web |quote=A 2015 US survey found that 98% of people with autoimmune diseases experienced fatigue, 89% said it was a "major issue", 68% said "fatigue is anything but normal. It is profound and prevents [them] from doing the simplest everyday tasks." and 59% said it was "probably the most debilitating symptom of having an AD. |url=https://autoimmune.org/fatigue-survey-results-released/ |title=Fatigue Survey Results Released |publisher=Autoimmune Association |date=23 March 2015 |access-date=23 May 2025 |archive-url=https://web.archive.org/web/20230106195924/https://autoimmune.org/fatigue-survey-results-released/ |archive-date=2023-01-06 }}</ref>
* [[blood disorders]], such as [[anemia]] and [[hemochromatosis]];<ref name="Cleveland Clinic medical professional 2022 z395">{{cite web | author=Cleveland Clinic medical professional | title=Blood Disorders: Types, Symptoms & Treatments | website=Cleveland Clinic | date=2022-12-07 | url=https://my.clevelandclinic.org/health/diseases/21545-blood-disorders | access-date=2024-05-04 | archive-date=2024-05-04 | archive-url=https://web.archive.org/web/20240504222259/https://my.clevelandclinic.org/health/diseases/21545-blood-disorders | url-status=live }}</ref><ref name="Hamilton 2022 g129">{{cite web | last=Hamilton | first=James Peter Adam | title=Hemochromatosis | website=Merck Manual Consumer Version | date=2022-09-06 | url=https://www.merckmanuals.com/en-ca/home/blood-disorders/iron-overload/hemochromatosis | access-date=2024-05-04 | archive-date=2024-05-07 | archive-url=https://web.archive.org/web/20240507141400/https://www.merckmanuals.com/en-ca/home/blood-disorders/iron-overload/hemochromatosis | url-status=live }}</ref>
* [[Traumatic brain injury|brain injury]];<ref>{{cite web |url=https://www.headway.org.uk/about-brain-injury/individuals/effects-of-brain-injury/fatigue/ | title=Fatigue after brain injury | access-date=2023-01-06 | archive-date=2023-01-06 | archive-url=https://web.archive.org/web/20230106185404/https://www.headway.org.uk/about-brain-injury/individuals/effects-of-brain-injury/fatigue/ | url-status=live }}</ref><ref>{{Cite web|url=https://www.bbc.com/future/article/20160817-the-daily-struggle-of-living-with-extreme-fatigue|title=The daily struggle of living with extreme fatigue|website=www.bbc.com|date=18 August 2016 |access-date=2024-03-30|archive-date=2024-03-30|archive-url=https://web.archive.org/web/20240330103010/https://www.bbc.com/future/article/20160817-the-daily-struggle-of-living-with-extreme-fatigue|url-status=live}}</ref>
* [[cancer]], in which case it is called [[cancer fatigue]];<ref>{{cite web |url=https://www.cancerresearchuk.org/about-cancer/coping/physically/fatigue/what-is-cancer-fatigue | title=What is cancer fatigue? &#124; Coping physically &#124; Cancer Research UK | access-date=2023-01-06 | archive-date=2023-01-06 | archive-url=https://web.archive.org/web/20230106185829/https://www.cancerresearchuk.org/about-cancer/coping/physically/fatigue/what-is-cancer-fatigue | url-status=live }}</ref>
* [[COVID-19]] and [[long COVID]];<ref>{{cite web |url=https://www.nhs.uk/conditions/coronavirus-covid-19/long-term-effects-of-coronavirus-long-covid/ | title=Long-term effects of coronavirus (Long COVID) | date=7 January 2021 | access-date=6 January 2023 | archive-date=9 May 2021 | archive-url=https://web.archive.org/web/20210509120337/https://www.nhs.uk/conditions/coronavirus-covid-19/long-term-effects-of-coronavirus-long-covid/ | url-status=live }}</ref>
* [[developmental disorder]]s such as [[autism spectrum|autism spectrum disorder]];<ref name="Williams Gotham p.">{{cite journal |last1=Williams |first1=Zachary J. |last2=Gotham |first2=Katherine O. |title=Current and lifetime somatic symptom burden among transition-aged autistic young adults |journal=Autism Research |date=April 2022 |volume=15 |issue=4 |pages=761–770 |doi=10.1002/aur.2671 |pmid=35019241 |pmc=9115676 }}</ref>
* [[endocrine disease]]s or [[metabolic disorder]]s: [[diabetes mellitus]], [[hypothyroidism]] and [[Addison's disease]];<ref name="Friedman">{{cite book |last1=Friedman |first1=Henry Harold |title=Problem-oriented Medical Diagnosis |date=2001 |publisher=Lippincott Williams & Wilkins |isbn=978-0-7817-2909-3 |pages=4–5 }}</ref>
* [[fibromyalgia]];<ref name="Beyond pain">{{cite journal |last1=Vincent |first1=Ann |last2=Benzo |first2=Roberto P |last3=Whipple |first3=Mary O |last4=McAllister |first4=Samantha J |last5=Erwin |first5=Patricia J |last6=Saligan |first6=Leorey N |title=Beyond pain in fibromyalgia: insights into the symptom of fatigue |journal=Arthritis Research & Therapy |date=2013 |volume=15 |issue=6 |page=221 |doi=10.1186/ar4395 |doi-access=free |pmid=24289848 |pmc=3978642 }}</ref>
* [[heart failure]] and [[heart attack]];<ref>{{cite journal |last1=Alsén |first1=Pia |last2=Brink |first2=Eva |last3=Brändström |first3=Yvonne |last4=Karlson |first4=Björn W |last5=Persson |first5=Lars-Olof |title=Fatigue after myocardial infarction: Relationships with indices of emotional distress, and sociodemographic and clinical variables |journal=International Journal of Nursing Practice |date=August 2010 |volume=16 |issue=4 |pages=326–334 |doi=10.1111/j.1440-172X.2010.01848.x |pmid=20649663 }}</ref>
* [[HIV]]<ref name="Fatigue Symptom Management">{{cite journal |last1=Perazzo |first1=Joseph D. |last2=Webel |first2=Allison R. |last3=Voss |first3=Joachim G. |last4=Prince-Paul |first4=Maryjo |title=Fatigue Symptom Management in People Living With Human Immunodeficiency Virus |journal=Journal of Hospice & Palliative Nursing |date=April 2017 |volume=19 |issue=2 |pages=122–127 |doi=10.1097/NJH.0000000000000329 |pmid=29398974 |pmc=5793939 }}</ref>
* [[Inborn error of metabolism|inborn errors of metabolism]] such as [[fructose malabsorption]];<ref>{{cite journal |last1=Whitehead |first1=William E. |last2=Palsson |first2=Olafur |last3=Jones |first3=Kenneth R. |title=Systematic review of the comorbidity of irritable bowel syndrome with other disorders: What are the causes and implications? |journal=Gastroenterology |date=April 2002 |volume=122 |issue=4 |pages=1140–1156 |doi=10.1053/gast.2002.32392 |pmid=11910364 |url=https://cdr.lib.unc.edu/downloads/zs25xj11x |archive-date=2022-07-04 |access-date=2024-03-30 |archive-url=https://web.archive.org/web/20220704082328/https://cdr.lib.unc.edu/downloads/zs25xj11x |url-status=live }}</ref><ref>{{cite journal | vauthors = Gibson PR, Newnham E, Barrett JS, Shepherd SJ, Muir JG | title = Review article: fructose malabsorption and the bigger picture | journal = Alimentary Pharmacology & Therapeutics | volume = 25 | issue = 4 | pages = 349–363 | date = February 2007 | pmid = 17217453 | doi = 10.1111/j.1365-2036.2006.03186.x | s2cid = 11487905 | doi-access =  }}</ref>
* [[infectious diseases]] such as [[infectious mononucleosis]] or [[tuberculosis]];<ref name=Friedman/>
* [[irritable bowel syndrome]];<ref name="Fatigue in irritable bowel syndrome">{{cite journal |last1=Norlin |first1=Anna-Karin |last2=Walter |first2=Susanna |last3=Icenhour |first3=Adriane |last4=Keita |first4=Åsa V. |last5=Elsenbruch |first5=Sigrid |last6=Bednarska |first6=Olga |last7=Jones |first7=Michael P. |last8=Simon |first8=Rozalyn |last9=Engström |first9=Maria |title=Fatigue in irritable bowel syndrome is associated with plasma levels of TNF-α and mesocorticolimbic connectivity |journal=Brain, Behavior, and Immunity |date=February 2021 |volume=92 |pages=211–220 |doi=10.1016/j.bbi.2020.11.035 |pmid=33249172 |url=http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-172690 |archive-date=2024-05-10 |access-date=2024-05-09 |archive-url=https://web.archive.org/web/20240510141559/https://liu.diva-portal.org/smash/record.jsf?pid=diva2%3A1519574&dswid=6955 |url-status=live }}</ref>
* [[kidney disease]]s, e.g., [[acute renal failure]], [[chronic renal failure]];<ref name=Friedman />
* [[leukemia]] or [[lymphoma]];{{medical citation needed|date=March 2024}}
* [[liver failure]] or liver diseases, e.g., [[hepatitis]];<ref name=Friedman/><ref name=Swain2006/>
* [[Hypotension|Low blood pressure]]
* [[Lyme disease]];{{medical citation needed|date=March 2024}}
* [[neurological disorder]]s such as [[narcolepsy]], [[Parkinson's disease]], [[Postural Orthostatic Tachycardia Syndrome|postural orthostatic tachycardia syndrome]] (POTS) and [[post-concussion syndrome]];{{medical citation needed|date=March 2024}}
* nutritional deficiencies, such as, [[Hyponatremia|sodium]], [[Iron-deficiency anemia|iron]], [[Vitamin B12 deficiency|vitamin B<sub>12</sub>]], and [[Folate deficiency|folate]] deficiencies
* [[physical trauma]] and other [[pain]]-causing conditions, such as [[arthritis]];{{medical citation needed|date=March 2024}}
* [[sleep deprivation]] or [[sleep disorder]]s, e.g. [[sleep apnea]];<ref name=Friedman/>
* [[stroke]]{{medical citation needed|date=March 2024}}
* [[thyroid disease]] such as [[hypothyroidism]];{{medical citation needed|date=March 2024}}
*sarcoidosis
*[[mast cell activation syndrome]]<ref name="PMID33261124">{{cite journal |vauthors=Valent P, Akin C, Nedoszytko B et al. |title=Diagnosis, Classification and Management of Mast Cell Activation Syndromes (MCAS) in the Era of Personalized Medicine |journal=International Journal of Molecular Sciences |volume=21 |issue=23 |date=2020-11-27 |doi=10.3390/ijms21239030 |pmc=7731385 |pmid=33261124 |pages=3 f |url=|doi-access=free}}</ref><ref name="PMID28262205">{{cite journal |vauthors=Afrin LB, Self S, Menk J, Lazarchick J |title=Characterization of Mast Cell Activation Syndrome |journal=The American Journal of the Medical Science |volume=353 |issue=3 |date=2017 |pages=207–215 |doi=10.1016/j.amjms.2016.12.013 |pmid=28262205|url=|doi-access=free|pmc=5341697 }}</ref><ref name="PMID38948000">{{cite journal |vauthors=Özdemir Ö, Kasımoğlu G, Bak A et al. |title=Mast cell activation syndrome: An up-to-date review of literature |journal=World J Clin Pediatr |date=2024-06-09 |volume=13 |issue=2 |doi=10.5409/wjcp.v13.i2.92813 |pmc=11212760 |pmid=38948000 |url=|doi-access=free}}</ref>

====Mental illnesses====
* [[anxiety disorder]]s, such as [[generalized anxiety disorder]];<ref name= DSM5>{{cite book | title=Diagnostic and statistical manual of mental disorders 5th edition: [[DSM-5]] | publisher=American Psychiatric Association | publication-place=Arlington, VA; Washington, D.C. | year=2013 | isbn=978-0-89042-555-8 | oclc=830807378 | page= [https://archive.org/details/diagnosticstatis0005unse/page/189 189–195]}}</ref>
* [[Major depressive disorder|depression]];<ref>{{Cite web|url=https://icd.who.int/browse/2024-01/mms/en#1194756772|title=ICD-11 for Mortality and Morbidity Statistics|website=icd.who.int|access-date=2024-03-26|archive-date=2024-02-23|archive-url=https://web.archive.org/web/20240223110155/https://icd.who.int/browse/2024-01/mms/en#1194756772|url-status=live}}</ref><ref name="pmid34599320"/>
* [[eating disorder]]s, which can produce fatigue due to inadequate nutrition;{{medical citation needed|date=March 2024}}

====Other====
* [[myalgic encephalomyelitis/chronic fatigue syndrome]] (ME/CFS)<ref>{{Cite journal |last1=Bateman |first1=Lucinda |last2=Bested |first2=Alison C. |last3=Bonilla |first3=Hector F. |last4=Chheda |first4=Bela V. |last5=Chu |first5=Lily |last6=Curtin |first6=Jennifer M. |last7=Dempsey |first7=Tania T. |last8=Dimmock |first8=Mary E. |last9=Dowell |first9=Theresa G. |last10=Felsenstein |first10=Donna |last11=Kaufman |first11=David L. |last12=Klimas |first12=Nancy G. |last13=Komaroff |first13=Anthony L. |last14=Lapp |first14=Charles W. |last15=Levine |first15=Susan M. |date=November 2021 |title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Essentials of Diagnosis and Management |journal=Mayo Clinic Proceedings |volume=96 |issue=11 |pages=2861–2878 |doi=10.1016/j.mayocp.2021.07.004 |doi-access=free |pmid=34454716 }}</ref>
* [[idiopathic chronic fatigue]], a term used to describe chronic fatigue which does not have symptoms of ME/CFS.<ref name="PMC6522773">{{cite journal |last1=Son |first1=Chang-Gue |title=Differential diagnosis between "chronic fatigue" and "chronic fatigue syndrome" |journal=Integrative Medicine Research |date=June 2019 |volume=8 |issue=2 |pages=89–91 |doi=10.1016/j.imr.2019.04.005 |pmid=31193269 |pmc=6522773 }}</ref><ref>{{cite journal |last1=van Campen |first1=C. (Linda) M. C. |last2=Visser |first2=Frans C. |title=Comparing Idiopathic Chronic Fatigue and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) in Males: Response to Two-Day Cardiopulmonary Exercise Testing Protocol |journal=Healthcare |date=5 June 2021 |volume=9 |issue=6 |page=683 |doi=10.3390/healthcare9060683 |doi-access=free |pmid=34198946 |pmc=8230194 }}</ref> However ICF does not have a dedicated diagnostic code in the [[World Health Organization]]'s [[ICD-11]] classification.<ref>{{Cite web|title=ICD-11 - Mortality and Morbidity Statistics {{!}} MG22 Fatigue|url=https://icd.who.int/browse11/l-m/en#/http://id.who.int/icd/entity/1109546957|date=2019|website=World Health Organization|access-date=2023-04-25|archive-date=2018-08-01|archive-url=https://archive.today/20180801205234/https://icd.who.int/browse11/l-m/en%23/http://id.who.int/icd/entity/294762853#/http://id.who.int/icd/entity/1109546957|url-status=live}}
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>{{cite journal |last1=Minshall |first1=D |title=Gulf War Syndrome: a review of current knowledge and understanding |journal=Journal of the Royal Naval Medical Service |date=December 2014 |volume=100 |issue=3 |pages=252–258 |doi=10.1136/jrnms-100-252 |pmid=25895403 }}</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>{{cite news |last1=Carter |first1=Jonathan L. |title=Fatigue in Patients With Multiple Sclerosis |url=https://practicalneurology.com/articles/2018-july-aug/fatigue-in-patients-with-multiple-sclerosis |work=Practical Neurology |date=2018 |archive-date=2022-06-16 |archive-url=https://web.archive.org/web/20220616230104/https://practicalneurology.com/articles/2018-july-aug/fatigue-in-patients-with-multiple-sclerosis |url-status=live }}</ref><ref>{{cite journal | vauthors = Chalah MA, Riachi N, Ahdab R, Créange A, Lefaucheur JP, Ayache SS | title = Fatigue in Multiple Sclerosis: Neural Correlates and the Role of Non-Invasive Brain Stimulation | journal = Frontiers in Cellular Neuroscience | volume = 9 | page = 460 | year = 2015 | pmid = 26648845 | pmc = 4663273 | doi = 10.3389/fncel.2015.00460 | doi-access = free }}</ref><ref name="Gerber et al 2019">{{cite journal | vauthors = Gerber LH, Weinstein AA, Mehta R, Younossi ZM | title = Importance of fatigue and its measurement in chronic liver disease | journal = World Journal of Gastroenterology | volume = 25 | issue = 28 | pages = 3669–3683 | date = July 2019 | pmid = 31391765 | pmc = 6676553 | doi = 10.3748/wjg.v25.i28.3669 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Hartvig Honoré P |title=Fatigue |journal=European Journal of Hospital Pharmacy |date=June 2013 |volume=20 |issue=3 |pages=147–148 |doi=10.1136/ejhpharm-2013-000309 |s2cid=220171226 |doi-access=free }}</ref><ref>{{cite journal |last1=Newland |first1=Pamela |last2=Starkweather |first2=Angela |last3=Sorenson |first3=Matthew |title=Central fatigue in multiple sclerosis: a review of the literature |journal=The Journal of Spinal Cord Medicine |date=3 July 2016 |volume=39 |issue=4 |pages=386–399 |doi=10.1080/10790268.2016.1168587 |pmid=27146427 |pmc=5102292 }}</ref><ref>{{cite journal |last1=Patejdl |first1=Robert |last2=Zettl |first2=Uwe K. |title=The pathophysiology of motor fatigue and fatigability in multiple sclerosis |journal=Frontiers in Neurology |date=27 July 2022 |volume=13 |article-number=891415 |doi=10.3389/fneur.2022.891415 |doi-access=free |pmid=35968278 |pmc=9363784 }}</ref> 
The ICD-11 MG22 definition of fatigue<ref>{{Cite web|url=https://icd.who.int/browse11/l-m/en#/http://id.who.int/icd/entity/1109546957|title=ICD-11 for Mortality and Morbidity Statistics|website=icd.who.int|access-date=2021-11-26|archive-date=2018-08-01|archive-url=https://archive.today/20180801205234/https://icd.who.int/browse11/l-m/en%23/http://id.who.int/icd/entity/294762853#/http://id.who.int/icd/entity/1109546957|url-status=live}}</ref> 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|date=March 2024}}

===Obesity===
Obesity correlates with higher fatigue levels and incidence.<ref>{{cite journal |last1=Resnick |first1=Helaine E. |last2=Carter |first2=Elizabeth A. |last3=Aloia |first3=Mark |last4=Phillips |first4=Barbara |title=Cross-Sectional Relationship of Reported Fatigue to Obesity, Diet, and Physical Activity: Results From the Third National Health and Nutrition Examination Survey |journal=Journal of Clinical Sleep Medicine |date=15 April 2006 |volume=02 |issue=2 |pages=163–169 |doi=10.5664/jcsm.26511 }}</ref><ref name="pmid15851643">{{cite journal |last1=Lim |first1=Weonjeong |last2=Hong |first2=Suzi |last3=Nelesen |first3=Richard |last4=Dimsdale |first4=Joel E. |title=The Association of Obesity, Cytokine Levels, and Depressive Symptoms With Diverse Measures of Fatigue in Healthy Subjects |journal=Archives of Internal Medicine |date=25 April 2005 |volume=165 |issue=8 |pages=910–915 |doi=10.1001/archinte.165.8.910 |pmid=15851643 }}</ref><ref>{{Cite web|url=https://www.nhs.uk/conditions/obesity/|title=Obesity|date=November 23, 2017|website=nhs.uk|access-date=March 21, 2024|archive-date=March 21, 2024|archive-url=https://web.archive.org/web/20240321100245/https://www.nhs.uk/conditions/obesity/|url-status=live}}</ref>

===Somatic symptom disorder===
In [[somatic symptom disorder]]<ref>{{cite web |url=https://bestpractice.bmj.com/topics/en-gb/571 | title=Evaluation of fatigue&nbsp;— Differential diagnosis of symptoms &#124; BMJ Best Practice US | access-date=2024-01-30 | archive-date=2023-06-04 | archive-url=https://web.archive.org/web/20230604030213/https://bestpractice.bmj.com/topics/en-gb/571 | url-status=live }}</ref> the patient is overfocused on a physical symptom, such as fatigue, that may or may not be explained by a medical condition.<ref>{{cite book |last1=D'Souza |first1=Ryan S. |last2=Hooten |first2=W. M. |title=StatPearls |date=2024 |publisher=StatPearls Publishing |chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK532253/ |chapter=Somatic Symptom Disorder |pmid=30335286 |access-date=2024-03-30 |archive-date=2023-05-31 |archive-url=https://web.archive.org/web/20230531103722/https://www.ncbi.nlm.nih.gov/books/NBK532253/ |url-status=live }}</ref><ref>{{Cite web|url=https://bestpractice.bmj.com/topics/en-gb/571#referencePop23|title=Evaluation of fatigue&nbsp;— Differential diagnosis of symptoms &#124; BMJ Best Practice US|website=bestpractice.bmj.com|access-date=2024-03-25|archive-date=2023-06-04|archive-url=https://web.archive.org/web/20230604030213/https://bestpractice.bmj.com/topics/en-gb/571#referencePop23|url-status=live}}</ref><ref>{{Cite web|url=https://www.mayoclinic.org/diseases-conditions/somatic-symptom-disorder/symptoms-causes/syc-20377776|title=Somatic symptom disorder&nbsp;— Symptoms and causes|website=Mayo Clinic|access-date=2024-03-25|archive-date=2024-03-26|archive-url=https://web.archive.org/web/20240326064219/https://www.mayoclinic.org/diseases-conditions/somatic-symptom-disorder/symptoms-causes/syc-20377776|url-status=live}}</ref>

===Scientifically unsupported causes===
The concept of [[adrenal fatigue]] is often raised in media but no scientific basis has been found for it.<ref>{{cite journal |last1=Cadegiani |first1=Flavio A. |last2=Kater |first2=Claudio E. |title=Adrenal fatigue does not exist: a systematic review |journal=BMC Endocrine Disorders |date=December 2016 |volume=16 |issue=1 |page=48 |doi=10.1186/s12902-016-0128-4 |pmid=27557747 |pmc=4997656 |doi-access=free }}</ref><ref name="webmd">{{cite web |last=Whitbourne |first=Kathryn |date=February 7, 2021 |title=Adrenal Fatigue: Is It Real? |url=http://www.webmd.com/a-to-z-guides/features/adrenal-fatigue-is-it-real |access-date=2014-03-19 |work=WebMD |publisher=Metcalf, Eric |archive-date=2017-10-02 |archive-url=https://web.archive.org/web/20171002103506/http://www.webmd.com/a-to-z-guides/features/adrenal-fatigue-is-it-real |url-status=live }}</ref><ref>{{cite journal |last1=Shah |first1=Rachna |last2=Greenberger |first2=Paul A. |title=Chapter 29: Unproved and controversial methods and theories in allergy-immunology |journal=Allergy and Asthma Proceedings |date=May 2012 |volume=33 |issue=3 |pages=100–102 |doi=10.2500/aap.2012.33.3562 |pmid=22794702 |quote=There is no scientific basis for the existence of this disorder and no conclusive method for diagnosis }}</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">{{Cite journal|title=Fatigue in inflammatory rheumatic disorders: pathophysiological mechanisms|first1=S Mechiel|last1=Korte|first2=Rainer H|last2=Straub|date=November 15, 2019|journal=Rheumatology|volume=58|issue=Suppl 5|pages=v35–v50|doi=10.1093/rheumatology/kez413|pmid=31682277|pmc=6827268}}</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>{{cite journal |last1=Korte |first1=S Mechiel |last2=Straub |first2=Rainer H |title=Fatigue in inflammatory rheumatic disorders: pathophysiological mechanisms |journal=Rheumatology |date=November 2019 |volume=58 |issue=Suppl 5 |pages=v35–v50 |doi=10.1093/rheumatology/kez413 |pmid=31682277 |pmc=6827268 }}</ref> and has been linked to many types of fatigue.<ref name="pmid31447842"/><ref>{{cite journal |last1=Omdal |first1=Roald |title=The biological basis of chronic fatigue: neuroinflammation and innate immunity |journal=Current Opinion in Neurology |date=June 2020 |volume=33 |issue=3 |pages=391–396 |doi=10.1097/WCO.0000000000000817 |pmid=32304437 |s2cid=215819309 }}</ref> Findings implicate [[neuroinflammation]] in the [[etiology]] of fatigue in [[Autoimmunity|autoimmune]] and related disorders.<ref name="pmid34599320"/><ref name="pmid31447842"/> Low-grade [[inflammation]] may cause an imbalance between energy availability and expenditure.<ref>{{cite journal | pmc=5932180 | year=2018 | last1=Lacourt | first1=T. E. | last2=Vichaya | first2=E. G. | last3=Chiu | first3=G. S. | last4=Dantzer | first4=R. | last5=Heijnen | first5=C. J. | title=The High Costs of Low-Grade Inflammation: Persistent Fatigue as a Consequence of Reduced Cellular-Energy Availability and Non-adaptive Energy Expenditure | journal=Frontiers in Behavioral Neuroscience | volume=12 | article-number=78 | doi=10.3389/fnbeh.2018.00078 | pmid=29755330 | doi-access=free }}</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>{{cite journal | doi=10.3389/fimmu.2017.00021 | doi-access=free | title=Role of Inflammation in Human Fatigue: Relevance of Multidimensional Assessments and Potential Neuronal Mechanisms | year=2017 | last1=Karshikoff | first1=Bianka | last2=Sundelin | first2=Tina | last3=Lasselin | first3=Julie | journal=Frontiers in Immunology | volume=8 | page=21 | pmid=28163706 | pmc=5247454 }}</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>{{Cite journal|title=A systematic review of cytokines in chronic fatigue syndrome/myalgic encephalomyelitis/systemic exertion intolerance disease (CFS/ME/SEID)|first1=Matthew|last1=Corbitt|first2=Natalie|last2=Eaton-Fitch|first3=Donald|last3=Staines|first4=Hélène|last4=Cabanas|first5=Sonya|last5=Marshall-Gradisnik|date=August 24, 2019|journal=BMC Neurology|volume=19|issue=1|page=207|doi=10.1186/s12883-019-1433-0|doi-access=free |pmid=31445522|pmc=6708220}}</ref>

===Reduced brain connectivity===
Fatigue has been correlated with reductions in structural and functional connectivity in the brain.<ref name="Qi-2019">{{Cite journal|title=Neural Mechanisms of Mental Fatigue Revisited: New Insights from the Brain Connectome|first1=Peng|last1=Qi|first2=Hua|last2=Ru|first3=Lingyun|last3=Gao|first4=Xiaobing|last4=Zhang|first5=Tianshu|last5=Zhou|first6=Yu|last6=Tian|first7=Nitish|last7=Thakor|first8=Anastasios|last8=Bezerianos|first9=Jinsong|last9=Li|first10=Yu|last10=Sun|date=April 1, 2019|journal=Engineering|volume=5|issue=2|pages=276–286|doi=10.1016/j.eng.2018.11.025|doi-access=free|bibcode=2019Engin...5..276Q }}</ref> This has included in post-stroke,<ref>{{Cite journal|title=Disruptions in Structural and Functional Connectivity Relate to Poststroke Fatigue|first1=Judith D.|last1=Schaechter|first2=Minhae|last2=Kim|first3=Baileigh G.|last3=Hightower|first4=Trevor|last4=Ragas|first5=Marco L.|last5=Loggia|date=February 28, 2023|journal=Brain Connectivity|volume=13|issue=1|pages=15–27|doi=10.1089/brain.2022.0021|pmid=35570655|pmc=9942175}}</ref> MS,<ref>{{Cite journal|title=Regional Brain Atrophy and Functional Connectivity Changes Related to Fatigue in Multiple Sclerosis|first1=Álvaro Javier|last1=Cruz Gómez|first2=Noelia|last2=Ventura Campos|first3=Antonio|last3=Belenguer|first4=César|last4=Ávila|first5=Cristina|last5=Forn|date=October 22, 2013|journal=PLOS ONE|volume=8|issue=10|article-number=e77914|doi=10.1371/journal.pone.0077914|doi-access=free |pmid=24167590|pmc=3805520|bibcode=2013PLoSO...877914C }}</ref> NMOSD and MOG,<ref name="pmid37180990"/> and ME/CFS.<ref>{{Cite journal|title=Abnormal Resting-State Functional Connectivity in Patients with Chronic Fatigue Syndrome: Results of Seed and Data-Driven Analyses|first1=Charles W.|last1=Gay|first2=Michael E.|last2=Robinson|first3=Song|last3=Lai|first4=Andrew|last4=O'Shea|first5=Jason G.|last5=Craggs|first6=Donald D.|last6=Price|first7=Roland|last7=Staud|date=February 1, 2016|journal=Brain Connectivity|volume=6|issue=1|pages=48–56|doi=10.1089/brain.2015.0366|pmid=26449441|pmc=4744887}}</ref> This was also found for fatigue after brain injury,<ref name="pmid35221951">{{Cite journal|title=Cingulo-Opercular and Frontoparietal Network Control of Effort and Fatigue in Mild Traumatic Brain Injury|first1=Amy E.|last1=Ramage|first2=Kimberly L.|last2=Ray|first3=Hannah M.|last3=Franz|first4=David F.|last4=Tate|first5=Jeffrey D.|last5=Lewis|first6=Donald A.|last6=Robin|date=January 30, 2021|journal=Frontiers in Human Neuroscience|volume=15|article-number=788091 |doi=10.3389/fnhum.2021.788091|doi-access=free |pmid=35221951|pmc=8866657 }}</ref> including a significant linear correlation between self-reported fatigue and brain functional connectivity.<ref name="pmid26878885">{{Cite journal|title=Post mTBI fatigue is associated with abnormal brain functional connectivity|first1=Love Engström|last1=Nordin|first2=Marika Christina|last2=Möller|first3=Per|last3=Julin|first4=Aniko|last4=Bartfai|first5=Farouk|last5=Hashim|first6=Tie-Qiang|last6=Li|date=February 16, 2016|journal=Scientific Reports|volume=6|issue=1|article-number=21183|doi=10.1038/srep21183|pmid=26878885 |pmc=4754765 |bibcode=2016NatSR...621183N }}</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>{{cite journal |last1=Borghetti |first1=Lorraine |last2=Rhodes |first2=L. Jack |last3=Morris |first3=Megan B. |title=Fatigue Leads to Dynamic Shift in Fronto-parietal Sustained Attention Network |journal=Proceedings of the Human Factors and Ergonomics Society Annual Meeting |date=September 2022 |volume=66 |issue=1 |pages=606–610 |doi=10.1177/1071181322661056 |s2cid=253205546 }}</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>{{cite journal | pmid=38551913 | date=2024 | author5=MacDougall NJJ | title=Brain connectivity changes underlying depression and fatigue in relapsing-remitting multiple sclerosis: A systematic review | journal=PLOS ONE | volume=19 | issue=3 | article-number=e0299634 | doi=10.1371/journal.pone.0299634 | doi-access=free | pmc=10980255 | vauthors = Kampaite A, Gustafsson R, York EN, Foley P | bibcode=2024PLoSO..1999634K }}</ref>

A small 2023 study found that infratentorial lesion volume (cerebellar and brainstem) was a relatively good predictor of RRMS fatigue severity.<ref>{{cite journal | pmid=37452063 | date=2023 | title=EDSS and infratentorial white matter lesion volume are considered predictors of fatigue severity in RRMS | journal=Scientific Reports | volume=13 | issue=1 | article-number=11404 | doi=10.1038/s41598-023-38368-3 | pmc=10349096 | vauthors = Ezzeldin MY, Mahmoud DM, Safwat SM, Soliman RK, Desoky T, Khedr EM | bibcode=2023NatSR..1311404E }}</ref>

===Damage to brain white matter===
Studies have found [[Signs and symptoms of multiple sclerosis#Fatigue|MS fatigue]] correlates with damage to NAWM (normal appearing [[white matter]]) (which will not show on normal [[Magnetic resonance imaging|MRI]] but will show on [[Diffusion MRI|DTI (diffusion tensor imaging)]]).<ref>{{cite journal |last1=Palotai |first1=Miklos |last2=Guttmann |first2=Charles RG |title=Brain anatomical correlates of fatigue in multiple sclerosis |journal=Multiple Sclerosis Journal |date=June 2020 |volume=26 |issue=7 |pages=751–764 |doi=10.1177/1352458519876032 |pmid=31536461 }}</ref><ref name="pmid37180990"/><ref>{{cite journal |last1=Preziosa |first1=Paolo |last2=Rocca |first2=Maria A. |last3=Pagani |first3=Elisabetta |last4=Valsasina |first4=Paola |last5=Amato |first5=Maria Pia |last6=Brichetto |first6=Giampaolo |last7=Bruschi |first7=Nicolò |last8=Chataway |first8=Jeremy |last9=Chiaravalloti |first9=Nancy D. |last10=Cutter |first10=Gary |last11=Dalgas |first11=Ulrik |last12=DeLuca |first12=John |last13=Farrell |first13=Rachel |last14=Feys |first14=Peter |last15=Freeman |first15=Jennifer |last16=Inglese |first16=Matilde |last17=Meani |first17=Alessandro |last18=Meza |first18=Cecilia |last19=Motl |first19=Robert W. |last20=Salter |first20=Amber |last21=Sandroff |first21=Brian M. |last22=Feinstein |first22=Anthony |last23=Filippi |first23=Massimo |title=Structural and functional magnetic resonance imaging correlates of fatigue and dual-task performance in progressive multiple sclerosis |journal=Journal of Neurology |date=March 2023 |volume=270 |issue=3 |pages=1543–1563 |doi=10.1007/s00415-022-11486-0 |pmid=36436069 |hdl=10026.1/20405 |url=https://discovery.ucl.ac.uk/id/eprint/10171992/20/Chataway_JOON-D-22-02550.R1.pdf |hdl-access=free }}</ref><ref>{{cite journal |last1=Novo |first1=Ana Margarida |last2=Batista |first2=Sonia |last3=Alves |first3=Carolina |last4=d'Almeida |first4=Otília C. |last5=Marques |first5=Inês Brás |last6=Macário |first6=Carmo |last7=Santana |first7=Isabel |last8=Sousa |first8=Lívia |last9=Castelo-Branco |first9=Miguel |last10=Cunha |first10=Luís |title=The neural basis of fatigue in multiple sclerosis: A multimodal MRI approach |journal=Neurology Clinical Practice |date=December 2018 |volume=8 |issue=6 |pages=492–500 |doi=10.1212/CPJ.0000000000000545 |pmid=30588379 |pmc=6294533 }}</ref><ref>{{cite journal |last1=Bisecco |first1=Alvino |last2=Caiazzo |first2=Giuseppina |last3=d'Ambrosio |first3=Alessandro |last4=Sacco |first4=Rosaria |last5=Bonavita |first5=Simona |last6=Docimo |first6=Renato |last7=Cirillo |first7=Mario |last8=Pagani |first8=Elisabetta |last9=Filippi |first9=Massimo |last10=Esposito |first10=Fabrizio |last11=Tedeschi |first11=Gioacchino |last12=Gallo |first12=Antonio |title=Fatigue in multiple sclerosis: The contribution of occult white matter damage |journal=Multiple Sclerosis Journal |date=November 2016 |volume=22 |issue=13 |pages=1676–1684 |doi=10.1177/1352458516628331 |pmid=26846989 }}</ref><ref>{{cite journal |last1=Rocca |first1=Maria A. |last2=Parisi |first2=Laura |last3=Pagani |first3=Elisabetta |last4=Copetti |first4=Massimiliano |last5=Rodegher |first5=Mariaemma |last6=Colombo |first6=Bruno |last7=Comi |first7=Giancarlo |last8=Falini |first8=Andrea |last9=Filippi |first9=Massimo |title=Regional but Not Global Brain Damage Contributes to Fatigue in Multiple Sclerosis |journal=Radiology |date=November 2014 |volume=273 |issue=2 |pages=511–520 |doi=10.1148/radiol.14140417 |pmid=24927473 }}</ref> The correlation becomes unreliable in patients aged over 65 due to damage due to ageing.<ref>{{cite journal |last1=Muñoz Maniega |first1=Susana |last2=Chappell |first2=Francesca M |last3=Valdés Hernández |first3=Maria C |last4=Armitage |first4=Paul A |last5=Makin |first5=Stephen D |last6=Heye |first6=Anna K |last7=Thrippleton |first7=Michael J |last8=Sakka |first8=Eleni |last9=Shuler |first9=Kirsten |last10=Dennis |first10=Martin S |last11=Wardlaw |first11=Joanna M |title=Integrity of normal-appearing white matter: Influence of age, visible lesion burden and hypertension in patients with small-vessel disease |journal=Journal of Cerebral Blood Flow & Metabolism |date=February 2017 |volume=37 |issue=2 |pages=644–656 |doi=10.1177/0271678X16635657 |pmid=26933133 |pmc=5381455 }}</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 [[Hsp90|HSP90α]], and a tendency to higher concentrations of HSP72.<ref>{{cite journal | pmc=4804286 | year=2016 | last1=Bårdsen | first1=K. | last2=Nilsen | first2=M. M. | last3=Kvaløy | first3=J. T. | last4=Norheim | first4=K. B. | last5=Jonsson | first5=G. | last6=Omdal | first6=R. | title=Heat shock proteins and chronic fatigue in primary Sjögren's syndrome | journal=Innate Immunity | volume=22 | issue=3 | pages=162–167 | doi=10.1177/1753425916633236 | pmid=26921255 }}</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">{{cite journal |last1=Grimstad |first1=Tore |last2=Kvivik |first2=Ingeborg |last3=Kvaløy |first3=Jan Terje |last4=Aabakken |first4=Lars |last5=Omdal |first5=Roald |title=Heat-shock protein 90 α in plasma reflects severity of fatigue in patients with Crohn's disease |journal=Innate Immunity |date=February 2020 |volume=26 |issue=2 |pages=146–151 |doi=10.1177/1753425919879988 |pmid=31601148 |pmc=7016405 }}</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>{{cite journal |last1=Norheim |first1=Katrine Brække |last2=Harboe |first2=Erna |last3=Gøransson |first3=Lasse G. |last4=Omdal |first4=Roald |title=Interleukin-1 Inhibition and Fatigue in Primary Sjögren's Syndrome&nbsp;– A Double Blind, Randomised Clinical Trial |journal=PLOS ONE |date=10 January 2012 |volume=7 |issue=1 |article-number=e30123 |doi=10.1371/journal.pone.0030123 |doi-access=free |pmid=22253903 |pmc=3254637 |bibcode=2012PLoSO...730123N }}</ref><ref>{{cite journal |last1=Omdal |first1=Roald |last2=Gunnarsson |first2=Ragnar |title=The effect of interleukin-1 blockade on fatigue in rheumatoid arthritis—a pilot study |journal=Rheumatology International |date=September 2005 |volume=25 |issue=6 |pages=481–484 |doi=10.1007/s00296-004-0463-z |pmid=15071755 }}</ref><ref>{{cite journal |last1=Skoie |first1=Inger Marie |last2=Bårdsen |first2=Kjetil |last3=Nilsen |first3=Mari M. |last4=Eidem |first4=Live E. |last5=Grimstad |first5=Tore |last6=Dalen |first6=Ingvild |last7=Omdal |first7=Roald |title=Fatigue and expression of heat-shock protein genes in plaque psoriasis |journal=Clinical and Experimental Dermatology |date=June 2022 |volume=47 |issue=6 |pages=1068–1077 |doi=10.1111/ced.15068 |pmid=34921435 }}</ref>

==Measurement==
Fatigue is currently measured by many different self-measurement surveys.<ref>{{cite journal |last1=Machado |first1=Myrela O. |last2=Kang |first2=Na-Young Cindy |last3=Tai |first3=Felicia |last4=Sambhi |first4=Raman D. S. |last5=Berk |first5=Michael |last6=Carvalho |first6=Andre F. |last7=Chada |first7=Lourdes P. |last8=Merola |first8=Joseph F. |last9=Piguet |first9=Vincent |last10=Alavi |first10=Afsaneh |title=Measuring fatigue: a meta-review |journal=International Journal of Dermatology |date=September 2021 |volume=60 |issue=9 |pages=1053–1069 |doi=10.1111/ijd.15341 |pmid=33301180 |hdl=11343/276722 |s2cid=228087205 |hdl-access=free }}</ref> Examples are the Fatigue Symptom Inventory (FSI)<ref>{{Cite journal|title=Comparative responsiveness and minimally important difference of Fatigue Symptom Inventory (FSI) scales and the FSI-3 in trials with cancer survivors|first1=Catherine E.|last1=Mosher|first2=Ekin|last2=Secinti|first3=Shelley A.|last3=Johns|first4=Kurt|last4=Kroenke|first5=Laura Q.|last5=Rogers|date=July 23, 2022|journal=Journal of Patient-Reported Outcomes|volume=6|issue=1|page=82|doi=10.1186/s41687-022-00488-1|doi-access=free |pmid=35870034|pmc=9308850}}</ref><ref>{{Cite web |url=http://www.cas.usf.edu/~jacobsen/HANDOUT.FSI%26MFSI.pdf |title=INFORMATION ABOUT THE FATIGUE SYMPTOM INVENTORY (FSI) AND THE MULTIDIMENSIONAL FATIGUE SYMPTOM INVENTORY (MFSI) |access-date=2024-04-30 |archive-date=2024-04-30 |archive-url=https://web.archive.org/web/20240430140611/http://www.cas.usf.edu/~jacobsen/HANDOUT.FSI%26MFSI.pdf |url-status=live }}</ref><ref>{{cite journal |last1=Mosher |first1=Catherine E. |last2=Secinti |first2=Ekin |last3=Johns |first3=Shelley A. |last4=Kroenke |first4=Kurt |last5=Rogers |first5=Laura Q. |title=Comparative responsiveness and minimally important difference of Fatigue Symptom Inventory (FSI) scales and the FSI-3 in trials with cancer survivors |journal=Journal of Patient-Reported Outcomes |date=December 2022 |volume=6 |issue=1 |page=82 |doi=10.1186/s41687-022-00488-1 |doi-access=free |pmid=35870034 |pmc=9308850 }}</ref> and the Fatigue Severity Scale.<ref>{{Cite web |url=https://www.med.upenn.edu/cbti/assets/user-content/documents/Fatigue%20Severity%20Scale%20(FSS).pdf |title=Fatigue Severity Scale (FSS) |access-date=2024-03-26 |archive-date=2023-01-30 |archive-url=https://web.archive.org/web/20230130005257/https://www.med.upenn.edu/cbti/assets/user-content/documents/Fatigue%20Severity%20Scale%20(FSS).pdf |url-status=live }}</ref><ref>{{cite journal |last1=Valko |first1=Philipp O. |last2=Bassetti |first2=Claudio L. |last3=Bloch |first3=Konrad E. |last4=Held |first4=Ulrike |last5=Baumann |first5=Christian R. |title=Validation of the Fatigue Severity Scale in a Swiss Cohort |journal=Sleep |date=November 2008 |volume=31 |issue=11 |pages=1601–1607 |doi=10.1093/sleep/31.11.1601 |pmid=19014080 |pmc=2579971 }}</ref><ref>{{Cite web |url=https://www.sralab.org/sites/default/files/2017-06/sleep-Fatigue-Severity-Scale.pdf |title=Fatigue Severity Scale (FSS) |access-date=2024-03-26 |archive-date=2024-03-29 |archive-url=https://web.archive.org/web/20240329105830/https://www.sralab.org/sites/default/files/2017-06/sleep-Fatigue-Severity-Scale.pdf |url-status=live }}</ref> There is no consensus on best practice,<ref>{{cite web |url=https://autoimmune.org/fatigue-survey-results-released/ | title=Fatigue Survey Results Released | date=23 March 2015 | access-date=6 January 2023 | archive-date=6 January 2023 | archive-url=https://web.archive.org/web/20230106195924/https://autoimmune.org/fatigue-survey-results-released/ | url-status=live }}</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 disease|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 [[Somatic symptom disorder|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 [[Myalgic encephalomyelitis/chronic fatigue syndrome|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.
* [[Anemia|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>{{Cite journal|title=The differential diagnosis of tiredness: a systematic review|first1=Rebekka|last1=Stadje|first2=Katharina|last2=Dornieden|first3=Erika|last3=Baum|first4=Annette|last4=Becker|first5=Tobias|last5=Biroga|first6=Stefan|last6=Bösner|first7=Jörg|last7=Haasenritter|first8=Christian|last8=Keunecke|first9=Annika|last9=Viniol|first10=Norbert|last10=Donner-Banzhoff|date=October 20, 2016|journal=BMC Family Practice|volume=17|issue=1|page=147|doi=10.1186/s12875-016-0545-5|doi-access=free |pmid=27765009 |pmc=5072300 }}</ref>

A 2014 Australian review recommended that a period of watchful waiting may be appropriate if there are no major warning signs.<ref>{{Cite web|url=https://www.racgp.org.au/afp/2014/july/fatigue|title=Fatigue&nbsp;– a rational approach to investigation|first=The Royal Australian College of general|last=Practitioners|website=Australian Family Physician|access-date=2024-03-27|archive-date=2024-03-27|archive-url=https://web.archive.org/web/20240327012439/https://www.racgp.org.au/afp/2014/july/fatigue|url-status=live}}</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">{{cite journal | vauthors = Nijrolder I, van der Windt D, de Vries H, van der Horst H | title = Diagnoses during follow-up of patients presenting with fatigue in primary care | journal = CMAJ | volume = 181 | issue = 10 | pages = 683–687 | date = November 2009 | pmid = 19858240 | pmc = 2774363 | doi = 10.1503/cmaj.090647 }}</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>{{cite journal |author1=Roald Omdal|author2=Svein Ivar Mellgren|author3= Katrine Brække Norheim|title=Pain and fatigue in primary Sjögren's syndrome |journal=Rheumatology |date=July 2021 |volume=6 |issue=7 |pages=3099–3106 |doi=10.1093/rheumatology/kez027|pmid=30815693 }}</ref><ref>{{Cite journal|title=Importance of fatigue and its measurement in chronic liver disease|first1=Lynn H|last1=Gerber|first2=Ali A|last2=Weinstein|first3=Rohini|last3=Mehta|first4=Zobair M|last4=Younossi|date=July 28, 2019|journal=World Journal of Gastroenterology|volume=25|issue=28|pages=3669–3683|doi=10.3748/wjg.v25.i28.3669|doi-access=free |pmid=31391765|pmc=6676553}}</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">{{cite journal | pmid=31447842 | year=2019 | last1=Zielinski | first1=M. R. | last2=Systrom | first2=D. M. | last3=Rose | first3=N. R. | title=Fatigue, Sleep, and Autoimmune and Related Disorders | journal=Frontiers in Immunology | volume=10 | article-number=1827 | doi=10.3389/fimmu.2019.01827 | pmc=6691096 | doi-access=free }}</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&nbsp;– other factors include [[sleep deprivation]] and overall health.<ref name="WebMD">{{cite news|title=Weakness and fatigue|newspaper=Webmd|url=http://www.webmd.com/a-to-z-guides/weakness-and-fatigue-topic-overview|publisher=Healthwise Inc.|access-date=2 January 2013|archive-date=30 December 2012|archive-url=https://web.archive.org/web/20121230140117/http://www.webmd.com/a-to-z-guides/weakness-and-fatigue-topic-overview|url-status=live}}</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>{{cite journal | vauthors = Gandevia SC | title = Spinal and supraspinal factors in human muscle fatigue | journal = Physiological Reviews | volume = 81 | issue = 4 | pages = 1725–1789 | date = October 2001 | pmid = 11581501 | doi = 10.1152/physrev.2001.81.4.1725 }}</ref> The central component of fatigue is triggered by an increase of the level of [[serotonin]] in the central nervous system.<ref name="pmid10919962">{{cite journal | vauthors = Davis JM, Alderson NL, Welsh RS | title = Serotonin and central nervous system fatigue: nutritional considerations | journal = The American Journal of Clinical Nutrition | volume = 72 | issue = 2 Suppl | pages = 573S–578S | date = August 2000 | pmid = 10919962 | doi = 10.1093/ajcn/72.2.573S | doi-access = free }}</ref> During motor activity, serotonin released in synapses that contact [[motor neuron]]s promotes [[muscle contraction]].<ref>{{cite journal | vauthors = Perrier JF, Delgado-Lezama R | title = Synaptic release of serotonin induced by stimulation of the raphe nucleus promotes plateau potentials in spinal motoneurons of the adult turtle | journal = The Journal of Neuroscience | volume = 25 | issue = 35 | pages = 7993–7999 | date = August 2005 | pmid = 16135756 | pmc = 6725458 | doi = 10.1523/JNEUROSCI.1957-05.2005 }}</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 [[Action potential|nerve impulse]] initiation and thereby muscle contraction are inhibited.<ref>{{cite journal | vauthors = Cotel F, Exley R, Cragg SJ, Perrier JF | title = Serotonin spillover onto the axon initial segment of motoneurons induces central fatigue by inhibiting action potential initiation | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 110 | issue = 12 | pages = 4774–4779 | date = March 2013 | pmid = 23487756 | pmc = 3607056 | doi = 10.1073/pnas.1216150110 | doi-access = free | bibcode = 2013PNAS..110.4774C }}</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>{{cite journal | vauthors = Enoka RM, Duchateau J | title = Muscle fatigue: what, why and how it influences muscle function | journal = The Journal of Physiology | volume = 586 | issue = 1 | pages = 11–23 | date = January 2008 | pmid = 17702815 | pmc = 2375565 | doi = 10.1113/jphysiol.2007.139477 | author-link = Roger M. Enoka }}</ref>

=====Mental=====  <!--Linked from [[Template:Mental processes]]-->

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>{{cite journal | vauthors = Lin H, Saunders B, Friese M, Evans NJ, Inzlicht M | title = Strong Effort Manipulations Reduce Response Caution: A Preregistered Reinvention of the Ego-Depletion Paradigm | journal = Psychological Science | volume = 31 | issue = 5 | pages = 531–547 | date = May 2020 | pmid = 32315259 | pmc = 7238509 | doi = 10.1177/0956797620904990 }}</ref>

Decreased attention can also be described as a more or less decreased [[level of consciousness]].<ref>{{cite book|title=Difficult Diagnosis 2| vauthors  = Giannini AJ |publisher=W.B. Saunders Co.|year=1991|isbn=978-0-7216-3481-4| veditors = Taylor RB |location= Philadelphia|page=156|chapter=Fatigue, Chronic|oclc=954530793}}</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">{{cite journal |vauthors=Possin KL, Moskowitz T, Erlhoff SJ, Rogers KM, Johnson ET, Steele NZ, Higgins JJ, Stiver J, Alioto AG, Farias ST, Miller BL, Rankin KP |title=The Brain Health Assessment for Detecting and Diagnosing Neurocognitive Disorders |journal=J Am Geriatr Soc |volume=66 |issue=1 |pages=150–156 |date=January 2018 |pmid=29355911 |pmc=5889617 |doi=10.1111/jgs.15208 |url=}}</ref><ref name="pmid30884965">{{cite journal |vauthors=Menzies V, Kelly DL, Yang GS, Starkweather A, Lyon DE |title=A systematic review of the association between fatigue and cognition in chronic noncommunicable diseases |journal=Chronic Illn |volume=17 |issue=2 |pages=129–150 |date=June 2021 |pmid=30884965 |pmc=6832772 |doi=10.1177/1742395319836472 |url=}}</ref><ref name="pmid38079429">{{cite journal |vauthors=Elliott TR, Hsiao YY, Randolph K, Urban RJ, Sheffield-Moore M, Pyles RB, Masel BE, Wexler T, Wright TJ |title=Efficient assessment of brain fog and fatigue: Development of the Fatigue and Altered Cognition Scale (FACs) |journal=PLOS ONE |volume=18 |issue=12 |article-number=e0295593 |date=2023 |pmid=38079429 |pmc=10712873 |doi=10.1371/journal.pone.0295593 |doi-access=free |bibcode=2023PLoSO..1895593E |url=}}</ref><!--It would also be interesting to read more about the ways in which the [[neurocognitive]] deficits of caused by fatigue differ from those caused by tiredness-->

The [[perception]] of mental fatigue is believed to be modulated by the brain's [[reticular activating system]] (RAS).<ref name="pmid24926625">{{cite journal |vauthors=Ishii A, Tanaka M, Watanabe Y |title=Neural mechanisms of mental fatigue |journal=Rev Neurosci |volume=25 |issue=4 |pages=469–79 |date=2014 |pmid=24926625 |doi=10.1515/revneuro-2014-0028 |url=}}</ref><ref name="pmid28690375">{{cite journal |vauthors=Garcia-Rill E, Virmani T, Hyde JR, D'Onofrio S, Mahaffey S |title=Arousal and the control of perception and movement |journal=Curr Trends Neurol |volume=10 |issue= |pages=53–64 |date=2016 |pmid=28690375 |pmc=5501251 |doi= |url=}}</ref><ref name="pmid31216564">{{cite journal |vauthors=Jones BE |title=Arousal and sleep circuits |journal=Neuropsychopharmacology |volume=45 |issue=1 |pages=6–20 |date=January 2020 |pmid=31216564 |pmc=6879642 |doi=10.1038/s41386-019-0444-2 |url=}}</ref><ref name="pmid37155119">{{cite journal |vauthors=Taran S, Gros P, Gofton T, Boyd G, Briard JN, Chassé M, Singh JM |title=The reticular activating system: a narrative review of discovery, evolving understanding, and relevance to current formulations of brain death |journal=Can J Anaesth |volume=70 |issue=4 |pages=788–795 |date=April 2023 |pmid=37155119 |pmc=10203024 |doi=10.1007/s12630-023-02421-6 |url=}}</ref><ref name="pmid31751025">{{cite book |last1=Arguinchona |first1=Joseph H. |last2=Tadi |first2=Prasanna |title=StatPearls |date=2024 |publisher=StatPearls Publishing |chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK549835/ |chapter=Neuroanatomy, Reticular Activating System |pmid=31751025 }}</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>{{cite web |title=Drowsy Driving is Impaired Driving |url=https://www.nsc.org/road-safety/safety-topics/fatigued-driving |website=National Safety Council |access-date=31 January 2019 |archive-date=1 February 2019 |archive-url=https://web.archive.org/web/20190201014026/https://www.nsc.org/road-safety/safety-topics/fatigued-driving |url-status=live }}</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">{{cite journal | vauthors = Hubbard AL, Golla H, Lausberg H | title = What's in a name? That which we call ''Multiple Sclerosis Fatigue'' | journal = Multiple Sclerosis | volume = 27 | issue = 7 | pages = 983–988 | date = June 2021 | pmid = 32672087 | pmc = 8142120 | doi = 10.1177/1352458520941481 }}</ref><ref>{{cite journal | vauthors = Mills RJ, Young CA, Pallant JF, Tennant A | title = Development of a patient reported outcome scale for fatigue in multiple sclerosis: The Neurological Fatigue Index (NFI-MS) | journal = Health and Quality of Life Outcomes | volume = 8 | page = 22 | date = February 2010 | pmid = 20152031 | pmc = 2834659 | doi = 10.1186/1477-7525-8-22 | doi-access = free }}</ref><ref>{{Cite web|url=https://www.tiktok.com/@msfighter101/video/7242002519809854763|title=TikTok&nbsp;— Make Your Day|website=www.tiktok.com|access-date=2024-03-26|archive-date=2024-03-26|archive-url=https://web.archive.org/web/20240326105609/https://www.tiktok.com/@msfighter101/video/7242002519809854763|url-status=live}}</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====

;{{vanchor|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">{{cite journal |last1=Piraino |first1=B. |last2=Vollmer-Conna |first2=U. |last3=Lloyd |first3=A.R. |title=Genetic associations of fatigue and other symptom domains of the acute sickness response to infection |journal=Brain, Behavior, and Immunity |date=May 2012 |volume=26 |issue=4 |pages=552–558 |doi=10.1016/j.bbi.2011.12.009 |pmid=22227623 |pmc=7127134 }}</ref> Other common causes of acute fatigue include [[Major depressive disorder|depression]] and chemical causes, such as [[dehydration]], [[poison]]ing, [[low blood sugar]], or [[Mineral (nutrient)|mineral]] or [[vitamin]] deficiencies.
;{{vanchor|Prolonged}}
:Prolonged fatigue is a self-reported, persistent (constant) fatigue lasting at least one month.<ref name="pmid34589772">{{cite journal |vauthors=Billones R, Liwang JK, Butler K, Graves L, Saligan LN |title=Dissecting the fatigue experience: A scoping review of fatigue definitions, dimensions, and measures in non-oncologic medical conditions |journal=Brain Behav Immun Health |volume=15 |issue= |article-number=100266 |date=August 2021 |pmid=34589772 |pmc=8474156 |doi=10.1016/j.bbih.2021.100266 |url=}}</ref><ref name="pmid18458765">{{cite journal |vauthors=Griffith JP, Zarrouf FA |title=A systematic review of chronic fatigue syndrome: don't assume it's depression |journal=Prim Care Companion J Clin Psychiatry |volume=10 |issue=2 |pages=120–8 |date=2008 |pmid=18458765 |pmc=2292451 |doi=10.4088/pcc.v10n0206 }}</ref>
;{{vanchor|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">{{cite journal | vauthors = Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, Komaroff A | title = The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group | journal = Annals of Internal Medicine | volume = 121 | issue = 12 | pages = 953–959 | date = December 1994 | pmid = 7978722 | doi = 10.7326/0003-4819-121-12-199412150-00009 | author-link2 = Stephen Straus | s2cid = 510735 | author-link = Keiji Fukuda | author-link6 = Anthony L. Komaroff }}</ref> Chronic fatigue is a symptom of many chronic illnesses and of [[idiopathic chronic fatigue]].<ref name="mitochondrial content">{{cite journal |last1=Wawrzyniak |first1=Nicholas R. |last2=Joseph |first2=Anna-Maria |last3=Levin |first3=David G. |last4=Gundermann |first4=David M. |last5=Leeuwenburgh |first5=Christiaan |last6=Sandesara |first6=Bhanuprasad |last7=Manini |first7=Todd M. |last8=Adhihetty |first8=Peter J. |title=Idiopathic chronic fatigue in older adults is linked to impaired mitochondrial content and biogenesis signaling in skeletal muscle |journal=Oncotarget |date=16 August 2016 |volume=7 |issue=33 |pages=52695–52709 |doi=10.18632/oncotarget.10685 |pmid=27447862 |pmc=5288142 }}</ref>

====By effect====

Fatigue can have significant negative impacts on quality of life.<ref>{{cite journal |last1=Mæland |first1=Elisabeth |last2=Miyamoto |first2=Samira T. |last3=Hammenfors |first3=Daniel |last4=Valim |first4=Valeria |last5=Jonsson |first5=Malin V. |title=Understanding Fatigue in Sjögren's Syndrome: Outcome Measures, Biomarkers and Possible Interventions |journal=Frontiers in Immunology |date=25 June 2021 |volume=12 |article-number=703079 |doi=10.3389/fimmu.2021.703079 |pmid=34249008 |doi-access=free |pmc=8267792 }}</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|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>{{cite journal |last1=Fredriksson-Larsson |first1=Ulla |last2=Alsen |first2=Pia |last3=Brink |first3=Eva |title=I've lost the person I used to be— Experiences of the consequences of fatigue following myocardial infarction |journal=International Journal of Qualitative Studies on Health and Well-being |date=January 2013 |volume=8 |issue=1 |article-number=20836 |doi=10.3402/qhw.v8i0.20836 |pmid=23769653 |pmc=3683631 }}</ref>

====WHO classification====
The [[World Health Organization]]'s [[ICD-11]] classification<ref name="ICD-11">{{Cite web|title=ICD-11 - Mortality and Morbidity Statistics {{!}} MG22 Fatigue|url=https://icd.who.int/browse11/l-m/en#/http://id.who.int/icd/entity/1109546957|date=2019|website=World Health Organization|access-date=2023-04-25|archive-date=2018-08-01|archive-url=https://archive.today/20180801205234/https://icd.who.int/browse11/l-m/en%23/http://id.who.int/icd/entity/294762853#/http://id.who.int/icd/entity/1109546957|url-status=live}}</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">{{cite journal |last1=Desai |first1=Geetha |last2=Sagar |first2=Rajesh |last3=Chaturvedi |first3=Santosh K |title=Nosological journey of somatoform disorders: From briquet's syndrome to bodily distress disorder |journal=Indian Journal of Social Psychiatry |date=2018 |volume=34 |issue=5 |page=29 |doi=10.4103/ijsp.ijsp_37_18 |doi-access=free }}</ref><ref name="pmid32701520">{{cite journal |last1=Basavarajappa |first1=Chethan |last2=Dahale |first2=Ajit Bhalchandra |last3=Desai |first3=Geetha |title=Evolution of bodily distress disorders |journal=Current Opinion in Psychiatry |date=September 2020 |volume=33 |issue=5 |pages=447–450 |doi=10.1097/YCO.0000000000000630 |pmid=32701520 |s2cid=220731306 }}</ref>

[[DSM-5]] lists 'fatigue or loss of energy nearly every day' as one factor in diagnosing depression.<ref>{{Cite web|url=https://www.psycom.net/depression/major-depressive-disorder/dsm-5-depression-criteria|title=Depression Definition and DSM-5 Diagnostic Criteria|date=August 26, 2022|website=www.psycom.net|access-date=March 21, 2024|archive-date=February 13, 2024|archive-url=https://web.archive.org/web/20240213040922/https://www.psycom.net/depression/major-depressive-disorder/dsm-5-depression-criteria|url-status=live}}</ref>

==Treatment and management==
Management may include review of factors and methods as explained below.{{citation needed|date=November 2025}}

===Cessation of medications causing fatigue===
Taking of medications with side effects of contributing to fatigue may be ceased.<ref>{{cite journal | vauthors = Siniscalchi A, Gallelli L, Russo E, De Sarro G | title = A review on antiepileptic drugs-dependent fatigue: pathophysiological mechanisms and incidence | journal = European Journal of Pharmacology | volume = 718 | issue = 1–3 | pages = 10–16 | date = October 2013 | pmid = 24051268 | doi = 10.1016/j.ejphar.2013.09.013 }}</ref>
<ref name="Mayo-Clinic-Fatigue-Causes-2023"/><ref>{{Cite web|url=https://www.health.harvard.edu/drugs-and-medications/what-to-do-when-medication-makes-you-sleepy|title=What to do when medication makes you sleepy|date=8 March 2016|access-date=9 November 2021|archive-date=9 November 2021|archive-url=https://web.archive.org/web/20211109140913/https://www.health.harvard.edu/drugs-and-medications/what-to-do-when-medication-makes-you-sleepy|url-status=live}}</ref>{{better source needed|date=November 2021}}<ref>{{cite journal | vauthors = Phansalkar S, van der Sijs H, Tucker AD, Desai AA, Bell DS, Teich JM, Middleton B, Bates DW | display-authors = 6 | title = Drug-drug interactions that should be non-interruptive in order to reduce alert fatigue in electronic health records | journal = Journal of the American Medical Informatics Association | volume = 20 | issue = 3 | pages = 489–493 | date = May 2013 | pmid = 23011124 | pmc = 3628052 | doi = 10.1136/amiajnl-2012-001089 }}</ref>

===Medications to treat fatigue===
{{See also|List of investigational fatigue drugs}}

The UK [[National Institute for Health and Care Excellence|NICE]] recommends consideration of [[amantadine]], [[modafinil]], and [[selective serotonin reuptake inhibitor]]s (SSRIs) for MS fatigue.<ref>{{Cite web|url=https://www.nice.org.uk/guidance/ng220/chapter/Recommendations#ms-symptom-management-and-rehabilitation|title=Recommendations &#124; Multiple sclerosis in adults: management &#124; Guidance &#124; NICE|date=June 22, 2022|website=www.nice.org.uk|access-date=January 7, 2023|archive-date=January 7, 2023|archive-url=https://web.archive.org/web/20230107085547/https://www.nice.org.uk/guidance/ng220/chapter/Recommendations#ms-symptom-management-and-rehabilitation|url-status=live}}</ref> A [[Patient-Centered Outcomes Research Institute|PCORI]] review, however, found amantadine, methylphenidate, and modafinil no more effective than placebo in reducing fatigue, with side effects reported.<ref>{{Cite web |date=2023-09-01 |title=Comparing Treatments for Multiple Sclerosis-Related Fatigue - Evidence Update for Clinicians |url=https://www.pcori.org/evidence-updates/comparing-treatments-multiple-sclerosis-related-fatigue |access-date=2024-12-26 |website=Patient-Centered Outcomes Research Institute (PCORI) |language=en |archive-date=2023-12-07 |archive-url=https://web.archive.org/web/20231207131308/https://www.pcori.org/evidence-updates/comparing-treatments-multiple-sclerosis-related-fatigue |url-status=live }}</ref> [[Psychostimulant]]s such as [[methylphenidate]], [[amphetamine-type stimulant|amphetamine]]s, and modafinil have been used in the treatment of fatigue related to [[depression (mood)|depression]],<ref name="pmid18425966">{{cite journal |vauthors=Candy M, Jones L, Williams R, Tookman A, King M |title=Psychostimulants for depression |journal=Cochrane Database Syst Rev |volume= |issue=2 |article-number=CD006722 |date=April 2008 |pmid=18425966 |doi=10.1002/14651858.CD006722.pub2 |url=}}</ref><ref name="pmid19281939">{{cite journal |vauthors=Hardy SE |title=Methylphenidate for the treatment of depressive symptoms, including fatigue and apathy, in medically ill older adults and terminally ill adults |journal=Am J Geriatr Pharmacother |volume=7 |issue=1 |pages=34–59 |date=February 2009 |pmid=19281939 |pmc=2738590 |doi=10.1016/j.amjopharm.2009.02.006 |url=}}</ref><ref name="pmid26906078">{{cite journal |vauthors=Malhi GS, Byrow Y, Bassett D, Boyce P, Hopwood M, Lyndon W, Mulder R, Porter R, Singh A, Murray G |title=Stimulants for depression: On the up and up? |journal=Aust N Z J Psychiatry |volume=50 |issue=3 |pages=203–207 |date=March 2016 |pmid=26906078 |doi=10.1177/0004867416634208 |s2cid=45341424 |url=}}</ref><ref name="pmid34144366">{{cite journal |vauthors=Bahji A, Mesbah-Oskui L |title=Comparative efficacy and safety of stimulant-type medications for depression: A systematic review and network meta-analysis |journal=J Affect Disord |volume=292 |issue= |pages=416–423 |date=September 2021 |pmid=34144366 |doi=10.1016/j.jad.2021.05.119 |url=}}</ref> and [[medical illness]] such as [[chronic fatigue syndrome]]<ref name="pmid20088743">{{cite journal |vauthors=Van Houdenhove B, Pae CU, Luyten P |title=Chronic fatigue syndrome: is there a role for non-antidepressant pharmacotherapy? |journal=Expert Opin Pharmacother |volume=11 |issue=2 |pages=215–223 |date=February 2010 |pmid=20088743 |doi=10.1517/14656560903487744 |s2cid=34827174 |url=}}</ref><ref name="pmid18505357">{{cite journal |vauthors=Valdizán Usón JR, Idiazábal Alecha MA |title=Diagnostic and treatment challenges of chronic fatigue syndrome: role of immediate-release methylphenidate |journal=Expert Rev Neurother |volume=8 |issue=6 |pages=917–927 |date=June 2008 |pmid=18505357 |doi=10.1586/14737175.8.6.917 |s2cid=37482754 |url=}}</ref> and [[cancer]].<ref name="pmid19281939" /><ref name="pmid8856815">{{cite journal |vauthors=Masand PS, Tesar GE |title=Use of stimulants in the medically ill |journal=Psychiatr Clin North Am |volume=19 |issue=3 |pages=515–547 |date=September 1996 |pmid=8856815 |doi=10.1016/s0193-953x(05)70304-x |url=}}</ref><ref name="pmid20870637">{{cite journal |vauthors=Breitbart W, Alici Y |title=Psychostimulants for cancer-related fatigue |journal=J Natl Compr Canc Netw |volume=8 |issue=8 |pages=933–942 |date=August 2010 |pmid=20870637 |doi=10.6004/jnccn.2010.0068 |url=|doi-access=free}}</ref><ref name="pmid21251796">{{cite journal |vauthors=Minton O, Richardson A, Sharpe M, Hotopf M, Stone PC |title=Psychostimulants for the management of cancer-related fatigue: a systematic review and meta-analysis |journal=J Pain Symptom Manage |volume=41 |issue=4 |pages=761–767 |date=April 2011 |pmid=21251796 |doi=10.1016/j.jpainsymman.2010.06.020 |url=|doi-access=free}}</ref><ref name="pmid24416225">{{cite journal |vauthors=Gong S, Sheng P, Jin H, He H, Qi E, Chen W, Dong Y, Hou L |title=Effect of methylphenidate in patients with cancer-related fatigue: a systematic review and meta-analysis |journal=PLOS ONE |volume=9 |issue=1 |article-number=e84391 |date=2014 |pmid=24416225 |pmc=3885551 |doi=10.1371/journal.pone.0084391 |bibcode=2014PLoSO...984391G |url=|doi-access=free}}</ref><ref name="pmid25299141">{{cite journal |vauthors=Yennurajalingam S, Bruera E |title=Review of clinical trials of pharmacologic interventions for cancer-related fatigue: focus on psychostimulants and steroids |journal=Cancer J |volume=20 |issue=5 |pages=319–324 |date=2014 |pmid=25299141 |doi=10.1097/PPO.0000000000000069 |s2cid=29351114 |url=}}</ref><ref name="pmid25814977">{{cite journal |vauthors=Dobryakova E, Genova HM, DeLuca J, Wylie GR |title=The dopamine imbalance hypothesis of fatigue in multiple sclerosis and other neurological disorders |journal=Front Neurol |volume=6 |issue= |page=52 |date=2015 |pmid=25814977 |pmc=4357260 |doi=10.3389/fneur.2015.00052 |url=|doi-access=free}}</ref> They have also been used to counteract fatigue in [[sleep loss]]<ref name="pmid16268386">{{cite journal |vauthors=Bonnet MH, Balkin TJ, Dinges DF, Roehrs T, Rogers NL, Wesensten NJ |title=The use of stimulants to modify performance during sleep loss: a review by the sleep deprivation and Stimulant Task Force of the American Academy of Sleep Medicine |journal=Sleep |volume=28 |issue=9 |pages=1163–1187 |date=September 2005 |pmid=16268386 |doi=10.1093/sleep/28.9.1163 |url=|doi-access=free}}</ref> and in [[aviation]].<ref name="pmid33754977">{{cite journal |vauthors=Ehlert AM, Wilson PB |title=Stimulant Use as a Fatigue Countermeasure in Aviation |journal=Aerosp Med Hum Perform |volume=92 |issue=3 |pages=190–200 |date=March 2021 |pmid=33754977 |doi=10.3357/AMHP.5716.2021 |s2cid=232325161 |url=}}</ref>

===Mental health tools===
[[Cognitive behavioral therapy|CBT]] can be useful for fatigue,<ref>{{cite journal |last1=Heins |first1=Marianne J. |last2=Knoop |first2=Hans |last3=Burk |first3=William J. |last4=Bleijenberg |first4=Gijs |title=The process of cognitive behaviour therapy for chronic fatigue syndrome: Which changes in perpetuating cognitions and behaviour are related to a reduction in fatigue? |journal=Journal of Psychosomatic Research |date=September 2013 |volume=75 |issue=3 |pages=235–241 |doi=10.1016/j.jpsychores.2013.06.034 |pmid=23972412 |hdl=2066/127332 |hdl-access=free }}</ref><ref name="auto2">{{Cite web|url=https://www.nhs.uk/live-well/sleep-and-tiredness/self-help-tips-to-fight-fatigue/|title=Self-help tips to fight tiredness|date=January 27, 2022|website=nhs.uk|access-date=January 31, 2024|archive-date=January 31, 2024|archive-url=https://web.archive.org/web/20240131103430/https://www.nhs.uk/live-well/sleep-and-tiredness/self-help-tips-to-fight-fatigue/|url-status=live}}</ref> including ME/CFS<ref>{{Cite journal|title=Does the effect of cognitive behavior therapy for chronic fatigue syndrome (ME/CFS) vary by patient characteristics? A systematic review and individual patient data meta-analysis|first1=T. A.|last1=Kuut|first2=L. M.|last2=Buffart|first3=A. M. J.|last3=Braamse|first4=I.|last4=Csorba|first5=G.|last5=Bleijenberg|first6=P.|last6=Nieuwkerk|first7=R.|last7=Moss-Morris|first8=F.|last8=Müller|first9=H.|last9=Knoop|date=February 28, 2024|journal=Psychological Medicine|volume=54|issue=3|pages=447–456|doi=10.1017/S0033291723003148|pmid=37927223|doi-access=free}}</ref><ref>{{cite journal |last1=Adamson |first1=James |last2=Ali |first2=Sheila |last3=Santhouse |first3=Alastair |last4=Wessely |first4=Simon |last5=Chalder |first5=Trudie |title=Cognitive behavioural therapy for chronic fatigue and chronic fatigue syndrome: outcomes from a specialist clinic in the UK |journal=Journal of the Royal Society of Medicine |date=October 2020 |volume=113 |issue=10 |pages=394–402 |doi=10.1177/0141076820951545 |pmid=32930040 |pmc=7583448 }}</ref> but is not included in [[National Institute for Health and Care Excellence|NICE]] guidelines for ME/CFS treatment.<ref>{{Cite web|url=https://www.nice.org.uk/guidance/ng206/chapter/Recommendations#symptom-management-for-people-with-mecfs|title=Recommendations &#124; Myalgic encephalomyelitis (or encephalopathy)/chronic fatigue syndrome: diagnosis and management &#124; Guidance &#124; NICE|date=October 29, 2021|website=www.nice.org.uk|access-date=April 28, 2024|archive-date=December 29, 2021|archive-url=https://web.archive.org/web/20211229193427/https://www.nice.org.uk/guidance/ng206/chapter/Recommendations#symptom-management-for-people-with-mecfs|url-status=live}}</ref><ref>{{Cite web|url=https://meassociation.org.uk/2023/11/the-me-association-raises-concerns-about-new-research-promoting-cbt-as-a-treatment-for-me-cfs/|title=The ME Association raises concerns about new research promoting CBT as a treatment for ME/CFS|first=Emma|last=Jefferies|date=November 6, 2023|website=The ME Association|access-date=April 28, 2024|archive-date=November 6, 2023|archive-url=https://web.archive.org/web/20231106230355/https://meassociation.org.uk/2023/11/the-me-association-raises-concerns-about-new-research-promoting-cbt-as-a-treatment-for-me-cfs/|url-status=live}}</ref>

===Other approaches===
====Avoidance of body heat====
Fatigue in [[Multiple sclerosis|MS]] often correlates with relatively high [[Endogeny|endogenous]] body temperature.<ref>{{Cite web|url=https://www.msaustralia.org.au/symptom/heat-sensitivity/|title=Heat Sensitivity|access-date=2024-03-15|archive-date=2024-01-17|archive-url=https://web.archive.org/web/20240117003926/https://www.msaustralia.org.au/symptom/heat-sensitivity/|url-status=live}}</ref><ref name="auto5"/><ref>{{Cite web|url=https://multiplesclerosisnewstoday.com/multiple-sclerosis-news/2014/08/11/higher-body-temperature-in-rrms-patients-could-cause-increased-fatigue/|title=Higher Body Temperature in RRMS Patients Could Cause Increased Fatigue|date=August 11, 2014|website=multiplesclerosisnewstoday.com|access-date=March 15, 2024|archive-date=March 15, 2024|archive-url=https://web.archive.org/web/20240315125742/https://multiplesclerosisnewstoday.com/multiple-sclerosis-news/2014/08/11/higher-body-temperature-in-rrms-patients-could-cause-increased-fatigue/|url-status=live}}</ref><ref>{{Cite journal|title=Body temperature is elevated and linked to fatigue in relapsing-remitting multiple sclerosis, even without heat exposure|first1=James F.|last1=Sumowski|first2=Victoria M.|last2=Leavitt|date=July 15, 2014|journal=Archives of Physical Medicine and Rehabilitation|volume=95|issue=7|pages=1298–1302|doi=10.1016/j.apmr.2014.02.004|pmid=24561056|pmc=4071126}}</ref><ref>{{cite journal |last1=Leavitt |first1=V. M. |last2=De Meo |first2=E. |last3=Riccitelli |first3=G. |last4=Rocca |first4=M. A. |last5=Comi |first5=G. |last6=Filippi |first6=M. |last7=Sumowski |first7=J. F. |title=Elevated body temperature is linked to fatigue in an Italian sample of relapsing–remitting multiple sclerosis patients |journal=Journal of Neurology |date=November 2015 |volume=262 |issue=11 |pages=2440–2442 |doi=10.1007/s00415-015-7863-8 |pmid=26223805 |hdl=2158/1428484 |hdl-access=free }}</ref><ref>{{cite journal | vauthors = Manjaly ZM, Harrison NA, Critchley HD, Do CT, Stefanics G, Wenderoth N, Lutterotti A, Müller A, Stephan KE | display-authors = 6 | title = Pathophysiological and cognitive mechanisms of fatigue in multiple sclerosis | journal = Journal of Neurology, Neurosurgery, and Psychiatry | volume = 90 | issue = 6 | pages = 642–651 | date = June 2019 | pmid = 30683707 | pmc = 6581095 | doi = 10.1136/jnnp-2018-320050 }}</ref><ref>{{cite journal | vauthors = Ellison PM, Goodall S, Kennedy N, Dawes H, Clark A, Pomeroy V, Duddy M, Baker MR, Saxton JM | display-authors = 6 | title = Neurostructural and Neurophysiological Correlates of Multiple Sclerosis Physical Fatigue: Systematic Review and Meta-Analysis of Cross-Sectional Studies | journal = Neuropsychology Review | volume = 32 | issue = 3 | pages = 506–519 | date = September 2022 | pmid = 33961198 | pmc = 9381450 | doi = 10.1007/s11065-021-09508-1 }}</ref><ref>{{cite journal | pmc=5102292 | date=2016 | title=Central fatigue in multiple sclerosis: A review of the literature | journal=The Journal of Spinal Cord Medicine | volume=39 | issue=4 | pages=386–399 | doi=10.1080/10790268.2016.1168587 | pmid=27146427 | vauthors = Newland P, Starkweather A, Sorenson M }}</ref><ref name="pmid35963205">{{cite journal |last1=Christogianni |first1=Aikaterini |last2=O'Garro |first2=Jasmine |last3=Bibb |first3=Richard |last4=Filtness |first4=Ashleigh |last5=Filingeri |first5=Davide |title=Heat and cold sensitivity in multiple sclerosis: A patient-centred perspective on triggers, symptoms, and thermal resilience practices |journal=Multiple Sclerosis and Related Disorders |date=November 2022 |volume=67 |article-number=104075 |doi=10.1016/j.msard.2022.104075 |pmid=35963205 |doi-access=free }}</ref><ref>{{Cite journal|title=Thermoregulation in multiple sclerosis|first1=Scott L.|last1=Davis|first2=Thad E.|last2=Wilson|first3=Andrea T.|last3=White|first4=Elliot M.|last4=Frohman|date=November 15, 2010|journal=Journal of Applied Physiology|volume=109|issue=5|pages=1531–1537|doi=10.1152/japplphysiol.00460.2010|pmid=20671034|pmc=2980380}}</ref><ref>{{cite book |doi=10.1016/B978-0-444-64074-1.00042-2 |chapter=Thermoregulatory dysfunction in multiple sclerosis |title=Thermoregulation: From Basic Neuroscience to Clinical Neurology, Part II |series=Handbook of Clinical Neurology |date=2018 |volume=157 |pages=701–714 |pmid=30459034 |isbn=978-0-444-64074-1 | vauthors = Davis SL, Jay O, Wilson TE |publisher=Elsevier }}</ref>{{Excessive citations inline|date=May 2024}}

====Improved sleep====
Improving sleep has been associated with reduced fatigue but only in small studies.<ref>{{cite journal |last1=Orlandi |first1=Aline Cristina |last2=Ventura |first2=Camila |last3=Gallinaro |first3=Andrea Lopes |last4=Costa |first4=Renata Alqualo |last5=Lage |first5=Laís Verderame |title=Improvement in pain, fatigue, and subjective sleep quality through sleep hygiene tips in patients with fibromyalgia |journal=Revista Brasileira de Reumatologia |date=October 2012 |volume=52 |issue=5 |pages=666–678 |pmid=23090368 }}</ref><ref>{{cite journal |last1=Pastier |first1=Nicholas |last2=Jansen |first2=Erica |last3=Boolani |first3=Ali |title=Sleep quality in relation to trait energy and fatigue: an exploratory study of healthy young adults |journal=Sleep Science |date=June 2022 |volume=15 |issue=S 02 |pages=375–379 |doi=10.5935/1984-0063.20210002 |pmid=35371410 |pmc=8906385 }}</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>{{Cite journal|title=Intermittent Fasting—Short- and Long-Term Quality of Life, Fatigue, and Safety in Healthy Volunteers: A Prospective, Clinical Trial|first1=Katharina|last1=Anic|first2=Mona W.|last2=Schmidt|first3=Larissa|last3=Furtado|first4=Lina|last4=Weidenbach|first5=Marco J.|last5=Battista|first6=Marcus|last6=Schmidt|first7=Roxana|last7=Schwab|first8=Walburgis|last8=Brenner|first9=Christian|last9=Ruckes|first10=Johannes|last10=Lotz|first11=Karl J.|last11=Lackner|first12=Annbalou|last12=Hasenburg|first13=Annette|last13=Hasenburg|date=October 10, 2022|journal=Nutrients|volume=14|issue=19|page=4216|doi=10.3390/nu14194216|doi-access=free |pmid=36235868|pmc=9571750}}</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">{{cite journal |last1=Tarn |first1=Jessica |last2=Evans |first2=Evelyn |last3=Traianos |first3=Emmanuella |last4=Collins |first4=Alexis |last5=Stylianou |first5=Mryto |last6=Parikh |first6=Jehill |last7=Bai |first7=Yang |last8=Guan |first8=Yu |last9=Frith |first9=James |last10=Lendrem |first10=Dennis |last11=Macrae |first11=Victoria |last12=McKinnon |first12=Iain |last13=Simon |first13=Bruce S. |last14=Blake |first14=Justyna |last15=Baker |first15=Mark R. |last16=Taylor |first16=John Paul |last17=Watson |first17=Stuart |last18=Gallagher |first18=Peter |last19=Blamire |first19=Andrew |last20=Newton |first20=Julia |last21=Ng |first21=Wan-Fai |title=The Effects of Noninvasive Vagus Nerve Stimulation on Fatigue in Participants With Primary Sjögren's Syndrome |journal=Neuromodulation: Technology at the Neural Interface |date=April 2023 |volume=26 |issue=3 |pages=681–689 |doi=10.1016/j.neurom.2022.08.461 |pmid=37032583 |doi-access=free }}</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>{{cite journal |last1=Xiang |first1=Yu |last2=Lu |first2=Liming |last3=Chen |first3=Xiankun |last4=Wen |first4=Zehuai |title=Does Tai Chi relieve fatigue? A systematic review and meta-analysis of randomized controlled trials |journal=PLOS ONE |date=5 April 2017 |volume=12 |issue=4 |article-number=e0174872 |doi=10.1371/journal.pone.0174872 |doi-access=free |pmid=28380067 |pmc=5381792 |bibcode=2017PLoSO..1274872X }}</ref><ref>{{cite journal |last1=Wang |first1=Rui |last2=Huang |first2=Xueyan |last3=Wu |first3=Yeqi |last4=Sun |first4=Dai |title=Efficacy of Qigong Exercise for Treatment of Fatigue: A Systematic Review and Meta-Analysis |journal=Frontiers in Medicine |date=22 June 2021 |volume=8 |article-number=684058 |doi=10.3389/fmed.2021.684058 |doi-access=free |pmid=34239889 |pmc=8257957 }}</ref><ref>{{cite book |doi=10.1016/bs.irn.2019.08.002 |chapter=Qigong exercise for chronic fatigue syndrome |title=Exercise on Brain Health |series=International Review of Neurobiology |date=2019 |volume=147 |pages=121–153 |pmid=31607352 |isbn=978-0-12-816967-4 | vauthors = Chan JS, Ng S, Yuen L, Chan CL |publisher=Academic Press }}</ref>

===Approaches to managing fatigue===
Some health systems help people manage their fatigue better through attitude changes and skills transference.<ref name="auto2"/><ref>{{Cite web|url=https://www.ruh.nhs.uk/rnhrd/patients/services/fatigue_services/index.asp?menu_id=1&RNHRD=y|title=Royal United Hospitals Bath NHS Foundation Trust|first=Royal United Hospitals Bath NHS Foundation|last=Trust|website=www.ruh.nhs.uk|access-date=2025-01-06|archive-date=2025-01-20|archive-url=https://web.archive.org/web/20250120122805/https://www.ruh.nhs.uk/rnhrd/patients/services/fatigue_services/index.asp?menu_id=1&RNHRD=y|url-status=live}}</ref><ref>{{Cite web|url=https://www.health.harvard.edu/topics/energy-and-fatigue#boosting-energy-managing-fatigue2|title=Energy & Fatigue|date=April 12, 2023|website=Harvard Health|access-date=January 6, 2025|archive-date=January 18, 2025|archive-url=https://web.archive.org/web/20250118080657/https://www.health.harvard.edu/topics/energy-and-fatigue#boosting-energy-managing-fatigue2|url-status=live}}</ref><ref>{{Cite web|url=https://www.mssociety.org.uk/about-ms/signs-and-symptoms/fatigue/managing-fatigue|title=Managing MS Fatigue - Help & Support &#124; MS Society|website=www.mssociety.org.uk|access-date=2025-01-06|archive-date=2025-01-06|archive-url=https://web.archive.org/web/20250106162801/https://www.mssociety.org.uk/about-ms/signs-and-symptoms/fatigue/managing-fatigue|url-status=live}}</ref><ref>{{Cite web|url=https://my.clevelandclinic.org/health/symptoms/21206-fatigue|title=Fatigue|website=Cleveland Clinic|access-date=2025-01-06|archive-date=2025-01-06|archive-url=https://web.archive.org/web/20250106162800/https://my.clevelandclinic.org/health/symptoms/21206-fatigue|url-status=live}}</ref><ref>{{Cite web|url=https://www.mayoclinic.org/diseases-conditions/cancer/in-depth/cancer-fatigue/art-20047709|title=Cancer fatigue: Why it occurs and how to cope|website=Mayo Clinic|access-date=2025-01-06|archive-date=2025-01-06|archive-url=https://web.archive.org/web/20250106162800/https://www.mayoclinic.org/diseases-conditions/cancer/in-depth/cancer-fatigue/art-20047709|url-status=live}}</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">{{cite web |title=Evaluation of fatigue&nbsp;— Differential diagnosis of symptoms |url=https://bestpractice.bmj.com/topics/en-us/571 |website=BMJ Best Practice |access-date=2024-03-25 |archive-date=2023-12-03 |archive-url=https://web.archive.org/web/20231203113928/https://bestpractice.bmj.com/topics/en-us/571 |url-status=live }}</ref><ref>{{cite journal |last1=Loge |first1=Jon Håvard |last2=Ekeberg |first2=Øivind |last3=Kaasa |first3=Stein |title=Fatigue in the general norwegian population |journal=Journal of Psychosomatic Research |date=July 1998 |volume=45 |issue=1 |pages=53–65 |doi=10.1016/s0022-3999(97)00291-2 |pmid=9720855 }}</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>{{Cite journal|title=Fatigue as the Chief Complaint|first1=Peter|last1=Maisel|first2=Erika|last2=Baum|first3=Norbert|last3=Donner-Banzhoff|date=August 30, 2021|journal=Deutsches Ärzteblatt International|volume=118|issue=33–34|pages=566–576|doi=10.3238/arztebl.m2021.0192|pmid=34196270|pmc=8579431}}</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>{{cite journal |last1=Meng |first1=Hongdao |last2=Hale |first2=Lauren |last3=Friedberg |first3=Fred |title=Prevalence and Predictors of Fatigue in Middle-Aged and Older Adults: Evidence from the Health and Retirement Study |journal=Journal of the American Geriatrics Society |date=October 2010 |volume=58 |issue=10 |pages=2033–2034 |doi=10.1111/j.1532-5415.2010.03088.x |pmid=20929479 |pmc=2981161 }}</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==
{{col div|colwidth=30em}}
* [[Acquiescence]]
* [[Affect (psychology)|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]]
{{colend}}

==References==
{{Reflist}}

==Further reading==
* [[Byung-Chul Han]]: ''Müdigkeitsgesellschaft''. Matthes & Seitz, Berlin 2010, {{ISBN|978-3-88221-616-5}}. (Philosophical essay about fatigue as a sociological problem and symptom).
** Danish edition: Træthedssamfundet. Møller, 2012, {{ISBN|978-87-994043-7-7}}.
** Dutch edition: De vermoeide samenleving. van gennep, 2012, {{ISBN|978-94-6164-071-0}}.
** Italian editions: La società della stanchezza. nottetempo, 2012, {{ISBN|978-88-7452-345-0}}.
** Korean edition: 한병철 지음 | 김태환 옮김. Moonji, 2011, {{ISBN|978-89-320-2396-0}}.
** Spanish edition: La sociedad del cansancio. Herder Editorial, 2012, {{ISBN|978-84-254-2868-5}}.
** South, David (1993). [https://www.google.co.uk/books/edition/Hannah_Institute_for_the_History_of_Medi/tyPYa2ZsItMC?hl=en&gbpv=1&dq=chronic+fatigue+hannah+institute&pg=PA1&printsec=frontcover ''Professor puts chronic fatigue into historical perspective''].  Hannah Institute for the History of Medicine Number 18 Summer 1993, p.&nbsp;1

==External links==
{{wikiquote}}
{{Commons category|Fatigue}}
* [http://www.cancer.gov/cancertopics/pdq/supportivecare/fatigue/patient Fatigue&nbsp;–  Information for Patients], U.S. National Cancer Institute
{{Medical resources
| ICD11          = {{ICD11|MG22}}
| ICD10          = {{ICD10|R|53||r|50}}
| ICD9           = {{ICD9|780.7}}
| ICDO           =
| OMIM           =
| DiseasesDB     = 30079
| MedlinePlus    = 003088
| eMedicineSubj  =
| eMedicineTopic =
| MeshID         = D005221
}}

{{General symptoms and signs}}
{{Common Cold}}
{{Mental processes}}

{{Authority control}}

[[Category:Exercise physiology]]
[[Category:Symptoms]]
[[Category:Subjective experience]]
[[Category:Fatigue| ]]