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Fatigue
Diagnosis/Condition:
Discipline:
ICD-9 Codes:
ICD-10 Codes:
Origination Date:
Review/Revised Date:
Next Review Date:
Malaise and fatigue
Chronic Fatigue Syndrome
Other malaise and fatigue
ND
780.7; 780.71; 780.79
R53.82; R53.2; G93.3; R93.3; R53.81;
R53.83
2007
10/2014
10/2016
Patient complaints of fatigue are common in clinical practice. Prevalence in population-based
surveys is between 6-7.5%. Statistics of those reporting significant fatigue in a primary care
setting is 21-33%.1,2,3,4,5,6,7 Complaints of fatigue have been documented in all age groups and
prevalence is generally higher in women.5,8,9,10 “Fatigue” is the 4th most common primary
diagnosis for patients seeking naturopathic care in the CHP Group.11 Fatigue itself is a factor in
presenteeism and fatigue accompanies many other causes of presenteeism, such as migraine,
back pain and depression.12 Fatigue is a significant complication of many clinical conditions and
treatment regimens and at the end of life. No two cases are the same, and there are usually other
co-morbidities and confounding factors to consider in evaluation, diagnosis and
treatment/management. Chronic fatigue syndrome (CFS) is a less frequent cause of fatigue, and
is briefly included in this summary.13,14
CFS is a condition thought to be associated with Epstein Barr virus (EBV) or another virus. It
may include no symptoms or it may manifest with symptoms such as: recurrent sore throat, low
grade fever, lymph node swelling, headache, muscle and joint pain, weakness, intestinal
discomfort, depression, and loss of concentration. It is often correlated to patients with
fibromyalgia and multiple chemical sensitivities and lasts longer than 6 months. The 1994
revised Centers for Disease Control (CDC) definition of the CFS states that patients “must have
clinically evaluated, unexplained, persistent or relapsing fatigue of new or definite onset; is not
the result of ongoing exertion; is not alleviated by rest; and results in substantial reduction in
previous levels of occupational, educational, social, or personal activities, plus four or more
specifically defined associated symptoms.” Chronic fatigue is considered a diagnosis of
exclusion. There are specific criteria to follow and they can be found here on the CDC website:
http://www.cdc.gov/cfs/
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Fatigue Clinical Pathway
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Subjective Findings and History15
The symptom of fatigue can be poorly described by the patient. A thorough evaluation is needed
to clarify complaints of “fatigue,” “tiredness,” or “exhaustion” and to distinguish lack of energy
from loss of motivation, sleepiness, or depression which may point to a different cause and/or
diagnosis. Fatigue described as loss of interest and enjoyment (anhedonia) for example, may be
an indicator of depression. Prominent sleepiness suggests a sleep disorder.
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A thorough history and intake should cover:
Systematic inquiry for personal or family history of diseases and medications often
associated with fatigue.
Symptoms of depression anxiety and sleep disorder.
Impact on activities of daily living (ADLs).
Patients' own understanding of their illness and how they cope with it.
Social stressors.
Length and duration of fatigue (less than one month - recent, over one monthprolonged, over six months-chronic). Chronic fatigue does not always translate to CFS.16
Concomitant symptoms (e.g. weight loss, night sweats) as an indicator for undiagnosed
chronic illness.
Screening for psychiatric disorders and/or domestic violence.
Pathophysiology
There are many causes of fatigue and sometimes the causative factor cannot be identified. 3,17,18,19
Some are associated with physical disease states such as rheumatoid conditions, autoimmune
disorders, such as lupus and multiple sclerosis, endocrine problems like hypothyroid, diabetes
and Addison’s disease, infections (influenza, tuberculosis (TB), AIDS, Hepatitis A, B, or C,
mononucleosis), cancers, and cardiovascular or renal disease. Psychosocial or mental health
issues like depression, insomnia or disturbed sleep, grief, and anxiety are common causes of
fatigue. Malnutrition from anorexia or eating disorders can also produce fatigue. End-of-life
stages also are frequently associated with fatigue. Fatigue is a common undesirable side effect
of many prescription and over the counter (OTC) medications, as well a recreational drugs
(including alcohol).
Objective Findings
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Examination—Both a physical and mental state examination must be performed to assess
medical and psychiatric diagnoses associated with fatigue.
Routine investigations—If there are no specific indications for special investigations, a
standard set of screening tests is adequate.
Special investigations—Immunological and virological tests are generally unhelpful as
routine investigations. Sleep studies can be useful in excluding a primary sleep disorder,
such obstructive sleep apnea and narcolepsy.
Psychological assessment—It is important to inquire fully about patients' understanding of
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Fatigue Clinical Pathway
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their illness (questions may include “What do you think is wrong with you?” and “What
do you think the cause is?”). Patients may be worried that the fatigue is a symptom of a
severe, as yet undiagnosed, disease or that activity will cause a long term worsening of
their condition and this may alter their health state.
Fatigue scales-- A large number of fatigue scales exist and there is no consensus on which
fatigue measuring scales that are most appropriate for use in assessment of fatigue in
different diseases.20
Assessment
An assessment that distinguishes predisposing, precipitating, and perpetuating factors is
valuable in providing an explanation to patients and for targeting intervention. Fatigue may
not always be sufficiently described as a simple continuum from no fatigue to severe fatigue,
and a multidimensional approach has been suggested, including physical, cognitive, emotional,
and functional axes.21
Exam
Complete physical exam (cardiovascular, head and neck, pulmonary, neurological, mental
status).
Labs
Common screening laboratory tests for fatigue:
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Complete Blood Count (CBC)
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Ferritin
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Erythrocyte sedimentation rate (ESR) and/or C reactive protein (CRP)
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Chemistry screen (comprehensive metabolic panel) including liver and kidney
function, glucose, and electrolytes
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Urea
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HIV, monospot , tuberculosis (PPD) based on history and risk factors
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Thyroid function panel (including Free T4)
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Urine Dipstick analysis, including glucose and beta hCG.
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Electrocardiogram (EKG)
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Fasting 2 hour Glucose Tolerance (2HGT) (if dysglycemia is suspected)
Special Tests
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Salivary cortisol testing for adrenal function 22,23,24,25,26,27
Stool analysis (dysbiosis)28
Heavy metals assessment 29
Lactulose/mannitol absorption test 29
Food allergy testing 29
Hepatitis Panel
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Fatigue Clinical Pathway
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Plan
There is no known specific medical therapy for the “cure” of CFS.30 The clinician-patient
relationship is of the utmost importance. Two-thirds of patients with CFS reported that they
were “dissatisfied with the quality of their medical care and felt their clinicians lacked
communication skills and education regarding their diagnosis”31. When CAM use was
compared between fatigued and non-fatigued persons, “those with CFS-like illness or chronic
fatigue were most likely to use body-based and mind-body therapies”.32
Explain the step-wise approach to assessment and clear establishment of mutual therapeutic
goals. Regularly scheduled brief appointments or communication should be planned in order to
monitor patient progress and maintenance of goals.
Natural therapeutics:
 The evidence for CAM treatments for fatigue comes primarily research on fatigue
associated with other conditions such as cancer, CFS, and end of life care. Sood et.al.
offer a critical review of 15 CAM interventions ranging from acupuncture and mistletoe
extract to Polarity Therapy and Tibetan yoga.33 They concluded that while, “…The
quality of the trials was highly variable, with heterogeneous outcomes, small sample
sizes, and a lack of randomization and blinding…” many studies reported favorable
results.
 Diaphragmatic breathing, good posture, relaxation, and bodywork (e.g. massage, spinal
manipulation) are all important stress relievers.
 Mild to moderate exercise (graded exercise therapy) stimulates the metabolism,
especially the digestive process, and increases nutrient absorption and toxin elimination
(e.g. tai chi, dance, walking, swimming, graded exercise therapy
(GET).34,35,36,37,38,39,40,41,42,43,44,45,126,Error! Bookmark not defined.,46,47,48,49
 Exercise in warm water.50
 Visualization and acupuncture (combined therapy).51
 Meditation, Qi Gong. 52,53,54,55,56,57
 Acupuncture.58
 Massage.59,60
 Homeopathy.61,62
 Sauna therapy.63
 Traditional Chinese Medicine.64,65
Diet and nutritional supplementation:
 A good diet that includes fruits, vegetables and grains and emphasizes whole, natural,
unprocessed selections. Fresh foods are preferable and frozen are acceptable.66
 Limit caffeine intake and increase water. Although caffeine can provide energy and
stimulation, regular intake may lead to fatigue.
 Essential fatty acids.67
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Fatigue Clinical Pathway
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Acclydine.68
Multivitamin/Multimineral (MVMM).
Magnesium and potassium supplementation.69,70,71,72,73,74,52,75,76,77,78,79,80 ,
Preliminary data on acetyl-l-carnitine and S-adenosylmethionine.52,81,82,83,84,85,86,52,87
Fiber stabilizes blood sugar - oat bran, apples, celery, grains (prevents reactive
hypoglycemia, common in EBV). Drink plenty of fluids (6-8 glasses of water daily).
Avoid canned foods and keep refined sugar to a minimum as it suppresses the immune
system.
Identify food allergies/sensitivities and limit intake of these foods.
Detoxification.88,89,90
Supplements such as: vitamins B12 and B691,92,93,94,95,96,97, NADH9899,100,101; DHEA102; betacarotene; which potentiates the immune system and acts as an anti-oxidant; vitamin C103;
which enhances the destruction of viruses and bacteria; zinc, which is necessary for
proper functioning of the thymus and for cellular immunity; and glandular extracts,
which enhance immune function.
Essential Fatty Acids(Evening Primrose Oil).104
Botanicals:
 Those that promote bile production, liver protection, liver regeneration, antioxidation,
and circulation. Examples are: Silybum marianum, Scutellaria baicalensis, catechin, Cynara
scolymus, Glycyrrhiza glabra105,106, Echinacea angustifolia, and Baptisia tinctoria.
 Adaptogenic herbs are often used in the treatment of fatigue in order to balance the
stress response in the body. This approach is often taken in the initial treatment
approach, while the cause of fatigue is being determined, as well as when there is
evidence of adrenal dysfunction. While there are several herbs with adaptogenic
qualities (e.g. Eleutherococcus senticosus 107, Paullinia sorbilis (guarana)108, Panax Ginseng,
Schisandra sp., Withania somnifera, and Rhodiola rosea109), individuals are ma110tched to the
herb(s) that best suits his/her symptoms.111,112,113,114,115,116,117
 Botanical medicine can also be used to support a patient receiving chemotherapy.118,119,120
 Anti-viral botanicals such as: Allium sativum, Lomatium porteri, Uncaria tomentosa,
Lentinula edodes (Shitake mushroom), Ganoderma lucidum, Sambucus nigra, Eleutherococcus
senticosus (Siberian ginseng), Hypericum perforatum, Atractylodes sp. formula (Chinese),
and Tang-Kuei Four Combination (Chinese).
Biopsychosocial approach:
Persistent fatigue requires active management, preferably before it has become chronic. When a
specific disease cause of fatigue can be identified, this should be the focus of treatment. If no
other specific disease diagnosis can be made, or if medical treatment of disease fails to relieve
the fatigue, a broader biopsychosocial management strategy is required. This is important as
well due to the lack of laboratory abnormalities, so patients and clinicians may struggle with the
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Fatigue Clinical Pathway
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validity of the disease and may experience feelings of guilt. Providing validation, support, and
reassurance to the patient is key.
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Managing activity and avoidance—Gradual increases in activity can be advised unless there
is a clear contraindication. It is critical, however, to distinguish between carefully graded
increases carried out in collaboration with the patient and “forced” exercise. It is also
important to explain that erratic variation between overactivity on “good” days and
subsequent collapse does not help long-term recovery and that “stabilizing” activity is a
prerequisite to graded increases.
Depression and anxiety—If there is evidence of depression a trial of an antidepressant drug
is warranted (e.g. tricyclic antidepressant (TCA,Selective serotonin reuptake inhibitors
(SSRIs, or Serotonin-norepinephrine reuptake inhibitors (SNRIs)).
Up to 50% of patients in one trial attributed their chronic fatigue to mainly psychological
causes.16 Randomised trials and systematic reviews have shown psychological therapies,
such as cognitive behavior therapy (CBT) to be equally effective for mild to moderate
depression (note: results are dependent on therapy type and clinician
experience).121,122,123,124,125,126 ,127,128,129,50,130
Managing occupational and social stresses—Patients may be overstressed by working. Those
who have left work may be inactive and demoralized and may not wish to return to the
same job. These situations require a problem solving approach to consider how to
manage work demands, achieve a return to work, or to plan an alternate career.131
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Pharmacological Agents for both fatigue and chronic fatigue syndrome include:
 Antidepressants (as described above), calcium-channel modulators, anti-virals and antiretrovirals, muscle relaxants, immune modulators, glucocorticoids, antibacterials, and
analgesics132
Referral Criteria
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Undiagnosed or suspected moderate- severe psychiatric disorder (including suicidal
ideation).
Suspected poor prognosis, or severe debilitating disease.
Worsening symptoms.
Resources for Clinicians (links to authoritative evidence-based information)
Brief Fatigue Inventory. This tool is designed for end of life, but physicians may find this tool
useful for evaluating fatigue. http://www.aafp.org/afp/20010901/807.html
Resources for Patients
Center for Disease Control and Prevention (CDC)
US Department of Health and Human Services
888-232-3228 (general CDC voice-mail which leads to CFS information) (www.cdc.gov/cfs)
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National CFS and Fibromyalgia Association
(www.ncfsfa.org)
eMedicineHealth.com is a first aid and consumer health information site written by physicians
for patients and consumers. Fatigue is a common health complaint. It is, however, one of the
hardest terms to define, and a symptom of many different conditions.
http://www.emedicinehealth.com/fatigue/article_em.htm
Mayo Clinic.com. Fatigue: When to rest, when to worry
http://www.mayoclinic.com/health/fatigue/HQ00673
Clinical Pathway Feedback
CHP desires to keep our clinical pathways customarily updated. If you wish to provide
additional input, please use the e-mail address listed below and identify which clinical pathway
you are referencing. Thank you for taking the time to give us your comments.
Clinical Services Department: [email protected]
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