Fatigue in Adults:​

Evaluation and Management

Kelly M. Latimer, MD, MPH;​Althea Gunther, MD;​and Michael Kopec, MD
Eastern Virginia Medical School, Norfolk, Virginia

Fatigue is among the top 10 reasons patients visit primary care offices, and it significantly affects patients’ well-being and
occupational safety. A comprehensive history and cardiopulmonary, neurologic, and skin examinations help guide the workup
and diagnosis. Fatigue can be classified as physiologic, secondary, or chronic. Physiologic fatigue can be addressed by proper
sleep hygiene, a healthy diet, and balancing energy expenditure. Secondary fatigue is improved by treating the underly-
ing condition. Cognitive behavior therapy, exercise therapy, and acupuncture may help with some of the fatigue associated
with chronic conditions. Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic, severe, and potentially
debilitating disorder with demonstrated inflammatory, neurologic, immunologic, and metabolic abnormalities. ME/CFS has a
poor prognosis, with no proven treatment or cure. It may become more common after the COVID-19 pandemic because many
patients with long COVID (post–COVID-19 condition) have symptoms similar to ME/CFS. The most important symptom of
ME/CFS is postexertional malaise. The 2015 National Academy of Medicine diagnostic criteria diagnose ME/CFS. Exercise can
be harmful to patients with ME/CFS because it can trigger postexertional malaise. Patients should be educated about pacing
their activity not to exceed their limited energy capacity. Treatment should prioritize comorbidities and symptoms based on
severity. (Am Fam Physician. 2023;​108(1):58-69. Copyright © 2023 American Academy of Family Physicians.)

Published online June 6, 2023. Fatigue encompasses a range of potential causes and
related comorbidities and is a feeling of weariness or
Fatigue is one of the top 10 reasons for a visit to primary exhaustion.12 This can be a physiologic, self-limited, normal
care and is reported by 5% to 10% of patients in the pri- response in healthy individuals. It may also be chronic or
mary care setting.1,2 Fatigue is the most common symptom secondary to another condition. Fatigue may or may not
reported by those with chronic illness. 3 A cross-sectional respond to rest. In comparison, sleepiness is the tendency
survey found up to 38% of U.S. workers reported fatigue to doze off and responds to rest.13 Patients, physicians, and
during the previous two weeks.4 Fatigue is strongly asso- medical journals use the words fatigue, sleepiness, and
ciated with absenteeism, decreased work productivity, and weakness interchangeably;​the three are often related and
serious accidents.5,6 Fatigue is estimated to cost employers not mutually exclusive. There are widely used objective
more than $100 billion per year.4 Risk factors for fatigue in
the general population include being female, unmarried,
younger, and of lower educational attainment.7 Fatigue BEST PRACTICES IN OCCUPATIONAL
is an important component of frailty syndrome, which is MEDICINE
commonly found in older patients with limited physiologic
reserves and vulnerability to minor illness or injury, and Recommendations From Choosing Wisely
independently predicts falls and functional decline in older Recommendation Sponsoring organization
people.8-10 Decreased cognition, some forms of cancer, met-
abolic and reproductive health effects, and increased mor- Do not routinely order sleep American College
studies (polysomnography) to of Occupational
tality have been associated with fatigue.9,11
screen for or diagnose sleep and Environmental
disorders in workers having Medicine
CME This clinical content conforms to AAFP criteria for chronic fatigue or insomnia.
CME. See CME Quiz on page 20.
Source:​For more information on Choosing Wisely, see https://​
Author disclosure:​ No relevant financial relationships. www.choosing​wisely.org. For supporting citations and to search
Choosing Wisely recommendations relevant to primary care, see
Patient information:​A handout on this topic is available
https://​w ww.aafp.org/pubs/afp/collections/choosing-wisely.html.
with the online version of this article.

58 American
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 FATIGUE IN ADULTS
TABLE 1

Diseases and Conditions Associated With Fatigue and Options for Evaluation
Category Disease/conditions Evaluation options

Cardiovascular Arrhythmias Chest computed tomography

and pulmonary Cardiomyopathy Chest radiography
Chronic obstructive pulmo- Echocardiography
nary disease Electrocardiography
Coronary artery disease Holter monitor
Heart failure Pulmonary function testing
Pulmonary hypertension
Sarcoidosis
Valvular heart disease

Endocrine and Chronic kidney disease A1C level

metabolic Diabetes mellitus Adrenocorticotropic hormone level
Hypercalcemia Basic metabolic panel
Hypercortisolism Cortisol level
Hyperthyroidism Renal ultrasonography
Hypothyroidism Thyroid-stimulating hormone level
Primary adrenal insufficiency Thyroid ultrasonography
Severe obesity Urinalysis

Environmental Adverse medication effect Alcohol screening (e.g., SBIRT [screening, brief
and exposure- Gulf War syndrome intervention, and referral to treatment])
related Chest radiography
Heavy metals
Mold/mycotoxins Lead level

Substance use disorder Medication levels

Urine drug screening

Gastrointestinal Celiac disease Abdominal computed tomography

Cirrhosis Comprehensive metabolic panel
Food allergy or intolerances* C-reactive protein
Inflammatory bowel diseases Endomysial antibody
Small intestinal bacterial Erythrocyte sedimentation rate
overgrowth* Liver ultrasonography
Tissue transglutaminase

Gynecologic Endometriosis Pelvic ultrasonography

Pregnancy Urine pregnancy test
Premenstrual syndrome

Hematologic Anemia Complete blood count

Iron overload Ferritin level
Folate level
Iron panel
Vitamin B12 level
continues

*—Comorbid conditions commonly found with myalgic encephalomyelitis/chronic fatigue syndrome.

and subjective tools to assess and monitor sleep- Evaluation

iness.13 In contrast, assessment tools for fatigue The differential diagnosis list for fatigue is exten-
are not consistently validated and tend to be con- sive (Table 1).15,16 Table 2 provides a list of ques-
dition specific.14 tions to ask when eliciting a history from a patient

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 FATIGUE IN ADULTS
TABLE 1 (continued)

Diseases and Conditions Associated With Fatigue and Options for Evaluation
Category Disease/conditions Evaluation options
Infectious Coccidioidomycosis Epstein-Barr virus antibody
diseases COVID-19 Hepatitis B antigen
Epstein-Barr virus* Hepatitis C antibody
Giardiasis HIV testing
Hepatitis B Lyme titer
Hepatitis C Monospot
HIV Purified protein derivative or quantiferon
Parvovirus B19 Rapid plasma reagin
Q fever Serum treponemal antibody
Syphilis Stool ova and parasites
Tick-borne diseases
Tuberculosis
West Nile virus
Neurologic Cerebrospinal fluid leak Acetylcholine receptor antibody
Cerebrovascular accident Brain or spine magnetic resonance imaging
Chiari malformation Electroencephalography
Craniocervical instability Methylmalonic acid level
Multiple sclerosis Vitamin B12 level
Myasthenia gravis
Parkinson disease
Seizures
Spinal stenosis
Traumatic brain injury
Vitamin B12 deficiency
Oncologic Primary cancers Bone scan
Secondary cancers Complete blood count with differential
Positron emission tomography/computed
tomography
Primary Anxiety* Generalized Anxiety Disorder 7-item screening tool
psychiatric Bipolar disorder Medication levels
Depression* Mood Disorder Questionnaire
Patient Health Questionnaire-9
Thyroid-stimulating hormone level
Rheumatologic Fibromyalgia* Anti-cyclic citrullinated peptides antibody
Polymyalgia rheumatica Antinuclear antibodies
Polymyositis C-reactive protein
Rheumatoid arthritis Creatine phosphokinase
Systemic lupus Erythrocyte sedimentation rate
erythematosus Radiography of affected joints
Rheumatoid factor
Sleep Narcolepsy Epworth Sleepiness Scale
Periodic limb movement Polysomnography
disorder* STOP-Bang (snoring, tired, observed, pres-
Sleep apnea* sure, body mass index, age, neck size, gender)
questionnaire
*—Comorbid conditions commonly found with myalgic encephalomyelitis/chronic fatigue syndrome.
Information from references 15 and 16.

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 FATIGUE IN ADULTS

with fatigue.16 Physicians should use validated however, only 27% were diagnosed with a con-
screening tools to rule out comorbid sleep, mood, dition that could explain the fatigue, the most
and substance use disorders. Figure 1 suggests common of which included anemia, vitamin B12
an approach to evaluating patients with fatigue. deficiency, infection, pregnancy, and psychiatric
Medications should be reviewed to ensure the diagnoses.17 In another study, only 8% of patients
fatigue is not iatrogenic. A physical including received a clear condition-based diagnosis one
cardiopulmonary, neurologic, and skin examina- year after their presentation to primary care
tions should be performed. The initial laboratory with fatigue. Nearly 17% received a psychological
workup should be guided by history, physical diagnosis.18
examination, and common causes of fatigue. Lab-
oratory testing without specific indications is not Physiologic Fatigue
high-yield and may only change treatment in 5% Physiologic fatigue, caused by an imbalance
of patients.17 between activities that burn energy and those
Despite a comprehensive workup, a definitive that restore energy, is a normal response relieved
diagnosis is often not made. In one study inves- by appropriate rest. Physiologic causes of fatigue
tigating first-time reports of fatigue in young should be assessed before investigating second-
adults without known comorbid conditions pre- ary or chronic fatigue.15,16,19 Physicians should
senting to primary care, most received a workup;​ inquire about the patient’s daily habits, including

TABLE 2

Questions for Eliciting a History From a Patient With Fatigue

History Sleep-related
Typical reaction to activity that was previously tolerated? Do you have any trouble falling asleep or staying asleep?
Any preceding triggers to the start of fatigue? After sleeping, do you feel rested?
Duration of symptoms? How would you describe your sleep quality?
Pattern of symptoms? Do you require more naps than other people?
Function Cognition-related
How would you rate your level of fatigue? Do you have problems performing the following activities?
What helps relieve your fatigue? Driving
What exacerbates your fatigue? Watching a movie
In what level of function can you participate? How does it Reading
compare with before you became sick? Completing timed complex tasks
How does your illness affect your ability to work and man- Following/participating in conversation
age household responsibilities?
Doing more than one thing at a time
How do you feel when you try to “push through” the fatigue?
Compare your work/school success before and after
Postexertional malaise becoming ill.
How do you feel after normal physical or emotional activity? Orthostasis
How much activity does it take you to feel ill? Describe how you feel when you have been standing still
What symptoms do you experience when standing or exert- for more than a few minutes.
ing yourself? What happens when you quickly change position from
How much time is required for recovery from physical or lying down or sitting to standing?
mental exertion? How long can you tolerate standing before feeling sick?
What activity avoidance or modification do you have to How does hot weather affect you?
make due to your illness?
Do you study or work in a reclined position? Why?

Adapted with permission from Bateman L, Bested AC, Bonilla HF, et al. Myalgic encephalomyelitis/chronic fatigue syndrome:​essentials of diag-
nosis and management. Mayo Clin Proc. 2021;​96(11):​2868.

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 FATIGUE IN ADULTS

the amount and quality of sleep, activity level limit screen time, and avoid caffeine and alcohol
throughout the day, and nutritional status. Inad- near bedtime.22 Excessive exercise of prolonged
equate sleep is a widespread problem, with nearly intensity and duration that depletes energy stores
30% of U.S. adults reporting fewer than seven and does not allow for adequate recovery can
hours of sleep per night.20 Patients at high risk of leave patients feeling fatigued.23 A prerequisite
obstructive sleep apnea should be screened using to having the energy to perform daily tasks is
a validated tool such as the STOP-Bang (snoring, consuming the nutritional components to create
tiredness, observed apnea, blood pressure, body this energy. Physicians should ask patients about
mass index, age, neck circumference, gender) their dietary habits and counsel them to avoid
questionnaire.21 Good sleep hygiene can contrib- fad diets or excessively restrictive meal regimens.
ute to more restorative sleep. Patients should be Ginseng may be helpful with nonspecific physio-
reminded to adhere to consistent sleep schedules, logic fatigue.24

FIGURE 1

Fatigue is the principal symptom

Perform a comprehensive history and physical examination

Exclude adverse medication effects
Exclude substance use disorder
Screen for a mood disorder (Table 1)
Screen for a sleep disorder (Table 1)
Consider ordering a basic laboratory workup (i.e., comprehensive
metabolic panel, complete blood count, thyroid-stimulating hormone
level, pregnancy test, erythrocyte sedimentation rate, and HIV test)

Consider phys- Evaluate and Discontinue Treat comorbid Optimize Perform additional testing based
iologic causes treat suspected suspected mood disorder treatment for on findings from the history and
and optimize sleep disorder medication existing comor- physical examination (Table 1)
sleep hygiene or substance bid conditions and address comorbid conditions

Persistent fatigue?

No Yes

Ensure frequent follow-up and monitoring

Perform additional evaluation based on

ongoing signs and symptoms (Table 1)

Persistent fatigue?

Consider myalgic encephalomyelitis/chronic fatigue syndrome (Figure 2)

Suggested approach for evaluating fatigue in primary care.

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 FATIGUE IN ADULTS

Secondary Fatigue to cancer,26 inflammatory conditions (e.g., rheu-

Fatigue is a common symptom of many disor- matoid arthritis, inflammatory bowel disease),27,28
ders. Treatment should target the underlying and neurologic conditions (e.g., multiple sclero-
condition. For example, pulmonary rehabilita- sis, myasthenia gravis).29,30 Exercise may improve
tion helps the respiratory symptoms of chronic fatigue and function related to fibromyalgia.31,32
obstructive pulmonary disease and also fatigue.25 Tai chi may be superior to aerobic exercise for
Exercise therapy and psychological interventions, those with fibromyalgia.33 Massage and acupunc-
specifically cognitive behavior therapy, have ture may help manage cancer-related fatigue.34,35
some evidence of effectiveness in fatigue related There is no evidence that pharmacologic treat-
ment targeting fatigue (e.g., modafinil, methyl-
phenidate) helps manage fatigue related to most
chronic diseases.36,37
TABLE 3
Chronic Fatigue
National Academy of Medicine Criteria
Fatigue lasting six months or longer is considered
for Diagnosing Myalgic Encephalomyelitis/
chronic. Many common diseases are associated
Chronic Fatigue Syndrome
with chronic fatigue.15 Most people with pro-
Required core symptoms (present for at least six tracted fatigue do not have chronic fatigue syn-
months, at least 50% of the time, with moderate to drome.18 However, when a patient has fatigue for
severe intensity):​ six months or longer, and physiologic and second-
Postexertional malaise (i.e., crash or postexertional ary causes are excluded, physicians should con-
symptom exacerbation)
sider a diagnosis of myalgic encephalomyelitis/
Profound fatigue of new onset with substantially chronic fatigue syndrome (ME/CFS).
decreased ability to engage in pre-illness levels of activ-
ity or function
Myalgic Encephalomyelitis/Chronic
Unrefreshing sleep
Fatigue Syndrome
Plus, at least one of the following:​
ME/CFS is a chronic, complex, multisystem,
Cognitive impairment (i.e., brain fog)
incompletely understood, and variably defined
Orthostatic intolerance (e.g., lightheadedness, nausea, condition with a poor prognosis.15 In 2015, the
fatigue, palpitations, syncope with prolonged standing)
National Academy of Medicine renamed the con-
Other common clues and associated symptoms (not
dition and published recommendations with evi-
part of the criteria):​
dence-based diagnostic criteria16,19,38 (Table 316,19).
Gastrointestinal or genitourinary symptoms
The diagnostic criteria have been widely adopted;​
Hypersensitivity to external stimuli (e.g., light, noise,
however, the name systemic exertional intoler-
chemicals, foods, drugs)
ance disease is not commonly used.15,16
Impaired immune function and increased susceptibility
to infection
DIAGNOSIS
Influenza-like symptoms (e.g., sore throat, lymphade-
nopathy, chills, fever) An ME/CFS diagnosis requires the patient to
Onset after an infectious episode (e.g., mononucleosis,
experience severe fatigue that produces a sub-
COVID-19) stantial decrease from pre-illness function. The
Respiratory issues (e.g., air hunger) secondary fatigue associated with most chronic
Thermoregulatory issues
diseases improves with exercise. In contrast,
patients with ME/CFS can experience a prolonged
Visual disturbances
worsening of symptoms with even a small increase
Widespread pain
in a previously tolerated activity. This is called
Adapted with permission from Committee on the Diagnostic Cri- postexertional malaise15,16 (Table 415,19). Patients
teria for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome;​ refer to it as a crash or relapse. Postexertional
Board on the Health of Select Populations;​Institute of Medicine.
Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. malaise can be provoked by physical exertion but
Redefining an Illness. National Academies Press;​2015:​210, with also by challenges in the emotional, cognitive,
additional information from reference 16. and sensory realms. The symptoms of postexer-
tional malaise are far more severe than expected

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 FATIGUE IN ADULTS

TABLE 4

Characteristics of Postexertional Malaise

Provoked by challenges in Symptoms Timing
any of the following areas:​ Exacerbation of any constellation of symptoms Immediately following trigger or may
Cognitive (e.g., cognitive, pain, sleep, influenza-like) be delayed by hours or days
Emotional Individual limits somewhat predictable;​can May last days, weeks, or months after
Environmental vary from day to day provoking incident

Orthostatic Severity out of proportion to stimulus Patient may never return to baseline

Physical Worsening function compared with baseline

Sensory

Information from references 15 and 19.

from simple overexertion by

a patient who is not phys- FIGURE 2
ically fit. Postexertional
malaise is the most import-
ant feature of ME/CFS and Patient presents with profound fatigue

distinguishes it from other

fatigue-causing conditions. Substantial decrease
There are no physical in function?
examination findings or
diagnostic tests for ME/CFS.
No Yes
It was previously a diag-
nosis of exclusion but now Manage symptoms Persist ≥ 6 months?
is a clinical diagnosis16,39 Consider another
(Figure 219). ME/CFS is not a diagnosis

psychological disorder and No Yes

is not caused by physical Manage symptoms Postexertional malaise

deconditioning, laziness, or Follow and reassess and unrefreshing sleep?
malingering. Patients with for 6 months
this disorder have debili- Consider another
diagnosis
tating symptoms and fre- No Yes

quently face stigma and Consider another Cognitive impairment or

skepticism from friends, diagnosis orthostatic intolerance?
family, and physicians.40
Patients often know more
No Yes
about ME/CFS than their
physicians, and many have Consider another Diagnose patient with
little trust in the medical diagnosis myalgic encephalomyelitis/
chronic fatigue syndrome
establishment.41
ME/CFS may be diffi-
cult to diagnose due to an
Diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome.
extensive differential, vari-
Adapted with permission from Committee on the Diagnostic Criteria for Myalgic Encepha-
able clinical presentations, lomyelitis/Chronic Fatigue Syndrome;​Board on the Health of Select Populations;​Institute
multiple possible comor- of Medicine. Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Redefining an
bid conditions, and a lack Illness. National Academies Press;​2015:​212.
of medical education and

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 FATIGUE IN ADULTS

awareness among physicians42 (Table 115,16). Any MEDICAL CARE

condition associated with chronic fatigue, chronic There is no U.S. Food and Drug Administra-
pain, autonomic dysfunction, or immune dysreg- tion–approved treatment for ME/CFS. 51 The
ulation can overlap with ME/CFS and cloud the most valuable action a physician can take for
clinical picture. a patient with this disorder is to validate their
concerns.15,16 A healthy patient-physician rela-
EPIDEMIOLOGY tionship is only possible when the patient feels
ME/CFS may affect 0.8% to 2.2% of the U.S. believed. The physician should treat symptoms
population, but most are undiagnosed or mis- in order of severity, with the patient setting the
diagnosed.43 The COVID-19 pandemic may priority 19 (Table 515,16,51-53). The goal of treatment
increase the prevalence because many patients should be to minimize symptoms and maximize
with long COVID (post–COVID-19 condition) function, which may include facilitating access
report long-lasting sequelae, including
chronic fatigue.44 Women are affected
three to four times more often than TABLE 5
men.43 Most patients are White, but
prevalence data are lacking in people Treatment Options for Symptoms of Myalgic
of color.15 The patient’s age at diagnosis Encephalomyelitis/Chronic Fatigue Syndrome
is bimodal, with a peak in the teenage Nonpharmacologic Pharmacologic treatments
years and another peak in the thirties, Symptom treatments (start at low doses)
but the condition has been described in
people from two to 77 years of age.16 Fatigue or Cognitive pacing Occasional use;​beware
brain fog of “push and crash”:​
Patients with ME/CFS and their Memory aids (e.g.,
family members report worse function calendar reminders, Amantadine
alarms, calculator) Armodafinil (Nuvigil)
and quality of life scores than patients
Perform cognitive
with other severe chronic diseases such Caffeine
tasks lying down
as multiple sclerosis.45,46 The severity Methylphenidate
of illness varies, with 25% of patients Modafinil
able to work. Between 10% and 25% are
homebound or bedbound.47 The most Gastrointes- Healthy diet If small intestinal bacte-
tinal Trial of elimination rial overgrowth:​
severely affected patients often cannot
diets (e.g., aspar- Metronidazole (Flagyl)
access medical care and are usually not
tame, sugar, dairy, Oral vancomycin
included in studies of ME/CFS. Other gluten-free)
patients have waxing and waning Rifaximin (Xifaxan)
symptoms and functional status. 47
Hypersen- Environmental controls None
sitivity to to reduce light levels,
PATHOPHYSIOLOGY stimuli sound levels, and tem-
Researchers have found abnormalities perature fluctuations
in energy metabolism in the nervous
Immune Avoid crowds Selective use:​
and immune systems in patients with
dysfunction Frequent hand washing Antiviral agents (e.g.,
ME/CFS.15,48 Patients exhibit impaired
Mask in public acyclovir)
generation and utilization of adenosine
Hydroxychloroquine
triphosphate, the key energy-storing
molecule in aerobic metabolism.49 Intravenous
immunoglobulin
When patients underwent maximal
Subcutaneous gamma
exercise over two consecutive days, the
globulin
patients with ME/CFS demonstrated continues
significantly impaired exercise perfor-
mance on day 2 compared with healthy Note:​Treatment should be individualized, symptom-based, and prioritized by
the patient.
participants and even patients with
multiple sclerosis.50

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 TABLE 5 (continued)

Treatment Options for Symptoms of Myalgic

Encephalomyelitis/Chronic Fatigue Syndrome
Nonpharmacologic Pharmacologic treatments to resources available to any severely
Symptom treatments (start at low doses)
disabled patient. Physicians should
Orthostatic Avoidance of pro- Alpha agonists treat any comorbidities and edu-
intolerance longed standing Desmopressin cate patients about pacing, where the
Compression stockings Fludrocortisone
patient stays within their finite energy
Electrolyte drinks capacity to avoid triggering postex-
Intravenous saline
Salt tablets ertional malaise. Patients can use the
Low-dose beta blocker
mantra “Stop, rest, pace.”15,16,19,54,55
Pain Acupuncture Antiepileptics Helpful pacing resources can be
Chiropractic therapy Medical marijuana
found at https://​w ww.meaction.net/
resource/pacing-and-management-
Dry needling Muscle relaxers
guide.54 The Centers for Disease Con-
Heat or cold packs Naltrexone (Revia)
trol and Prevention website provides
Hydrotherapy Nonsteroidal anti-
patient-centered handouts at https://​
Massage inflammatory drugs
w w w.c d c . gov/me - c f s /re s ou rc e s /
Pacing Serotonin and nor-
epinephrine reuptake
patient-toolkit.html.55
Physical therapy inhibitors Treatment must be individualized
Transcutaneous elec- Tramadol because every patient with ME/CFS
trical nerve stimulation has different symptoms. Polyphar-
macy can become a problem, so using
Postexertional Assistive devices (e.g., None
malaise scooter, shower chair, medications with more than one
stair lift) therapeutic effect is helpful (e.g., pre-
Avoid triggers scribing a tricyclic antidepressant to
Disability benefits help with both poor sleep and pain).
Handicap parking
Frequent medication reconciliation
placard is imperative. Patients may be sen-
Home health aide sitive to adverse medication effects;​
Pacing
therefore, lower doses to start should
be considered and increased slowly
Use symptom journal
or activity tracker to as indicated.
learn limits Regularly scheduled visits foster
Work or school the patient-physician partnership
accommodations and help continually reassess and
optimize symptom-directed therapy.
Sleep Blue-light filter Alpha blockers Physicians should offer telemedicine
problems Ear plugs Antiepileptics visits because even an outing to a phy-
Eye masks Antihistamines sician’s office may trigger postexer-
Good sleep hygiene Benzodiazepines tional malaise. Because many of these
Light therapy Eszopiclone (Lunesta) patients are homebound, telemedicine
Meditation and relax- Low-dose tricyclic can help them access much-needed
ation techniques antidepressants care. Specialists should be consulted
Mirtazapine as needed and could include psychol-
Muscle relaxers ogy, pain medicine, physiatry, occu-
Suvorexant (Belsomra) pational therapy, physiotherapy, and
Trazodone
sleep medicine.52
Zolpidem
OUTDATED RECOMMENDATIONS
Note:​Treatment should be individualized, symptom-based, and prioritized by AND CONTROVERSY
the patient.
In 2011, the PACE trial reported that
Information from references 15, 16, and 51-53. graded exercise therapy and cogni-
tive behavior therapy were effective

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 FATIGUE IN ADULTS

SORT:​KEY RECOMMENDATIONS FOR PRACTICE

Evidence
Clinical recommendation rating Comments

Evaluate for physiologic causes of fatigue before investi- C Expert opinion and consen-
gating secondary or chronic fatigue.15,16,19 sus guidelines

Use exercise therapy and psychological interventions (par- B Limited-quality patient-

ticularly cognitive behavior therapy) to treat fatigue related oriented evidence
to cancer, inflammatory conditions, neurologic conditions,
and fibromyalgia, but not ME/CFS.15,16,19,26-33,36,51,52

Use the National Academy of Medicine criteria to diagnose C Consensus guideline

ME/CFS.19,38 informed by systematic
review

When treating ME/CFS, target the most severe symptoms C Expert opinion and consen-
and comorbidities.15,16,19,51,52 sus guidelines

Educate patients with ME/CFS about pacing, which may C Expert opinion and consen-
prevent postexertional malaise.15,16,19 sus guidelines

ME/CFS = myalgic encephalomyelitis/chronic fatigue syndrome.

A = consistent, good-quality patient-oriented evidence;​ B = inconsistent or limited-quality patient-oriented evidence;​
C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the
SORT evidence rating system, go to https://​w ww.aafp.org/afpsort.

treatments for patients with ME/CFS.56 The study

was later found to have significant methodologic The Authors
flaws and investigator-related conflicts of inter- KELLY M. LATIMER, MD, MPH, FAAFP, is an asso-
est.57 Reanalyzed data showed no benefit of inter- ciate professor of family and community medicine
ventions and showed harms in the graded exercise at Eastern Virginia Medical School, Norfolk, Va.
therapy group.58 Importantly, exercise is no lon-
ALTHEA GUNTHER, MD, is an assistant professor
ger recommended by the U.S. ME/CFS Clinician of family and community medicine at Eastern
Coalition and is likely to be harmful compared Virginia Medical School.
with standard care.15,16,59 Cognitive behavior ther-
apy may be as helpful as it would be for anyone MICHAEL KOPEC, MD, is an assistant professor of
family and community medicine at Eastern Vir-
with a chronic debilitating disease, but it does not ginia Medical School.
help with fatigue.
This article updates previous articles on this topic by Address correspondence to Kelly M. Latimer, MD,
Yancey and Thomas,60 Rosenthal, et al.,61 and Craig MPH, FAAFP, Eastern Virginia Medical School,
and Kakumanu.62 Department of Family Medicine, 825 Fairfax Ave.,
Norfolk, VA 23507 (email:​latimekm@​evms.edu).
Data Sources:​A search was completed in PubMed Reprints are not available from the authors.
using the key terms fatigue, sleepiness, screening for
obstructive sleep apnea, myalgic encephalomyelitis/
chronic fatigue syndrome. Additional terms included References
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