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Day # 126: Chronic Fatigue Syndrome

Today we will continue our current theme of psychosomatic disorders as we discuss chronic fatigue syndrome.

Today's Content Level: Intermediate; Advanced


  • Chronic fatigue syndrome (CFS) is an illness of uncertain cause that is characterized by disabling fatigue and other symptoms such as cognitive impairment, orthostatic intolerance, sleep disturbances, and headaches.

  • CFS is also known by other names including myalgic encephalomyelitis (ME) and systemic exertion intolerance disease (SEID).

  • CFS is a controversial diagnosis and there is debate regarding the validity of the disease. It shares common features with other disorders including fibromyalgia, irritable bowel syndrome, and multiple chemical sensitivity.

Diagnostic Criteria 1 , 2

  • There are multiple case definitions, however the Institute of Medicine (IOM) diagnostic criteria focuses on the most specific features of the disease.

  • There are three core/required symptoms to diagnose CFS:

  • ≥ 6 months of significantly reduced ability to perform activities that were normal before the illness. This reduced ability to engage in activities is also associated with profound fatigue and not substantially alleviated by rest. The extent of fatigue was not a problem before becoming ill. Activities may include occupational, family, social, or physical tasks and responsibilities.

  • Post-exertional malaise (PEM): worsening of CFS symptoms after physical, emotional, or mental exertion that would not have caused a problem before the illness. Patients often describe PEM as a "crash", "collapse", or "relapse". Symptoms of PEM may last days or even weeks. Example-> attending a child's school event may leave someone house-bound for days in a row and be unable to perform home tasks like cooking or laundry.

  • Un-refreshing sleep: may not feel better or less tired, even after a full night of sleep. Some people with CFS may have problems falling asleep or staying asleep.

  • In addition to the three core symptoms, one of the following two symptoms is required for diagnosis:

  • Cognitive impairment: problems with thinking, memory, attention, information processing, or executive functioning. Most individuals with CFS have trouble thinking quickly, remembering things, and paying attention to details. Patients may describe this problem as "brain fog". All of these symptoms can be exacerbated by exertion, effort, stress, or prolonged upright posture.

  • Orthostatic intolerance: patients with CFS experience a worsening of symptoms while standing or sitting upright. Symptoms may include feeling lightheaded, dizzy, weak, fainting, headaches, nausea, blurry vision, or increased fatigue or cognitive worsening. Symptoms may improve, but not necessarily fully resolve, with lying down. They may have objective heart rate and blood pressure abnormalities while standing and have abnormal orthostatic vital signs or head-tilt testing.

Other Common Symptoms 3

  • Many, but not all, individuals with ME/CFS have other associated symptoms. Some of the most common symptoms include:

  • Chronic pain or muscle weakness (muscle pain, joint pain, headaches)

  • Sore throat

  • Tender lymph nodes

  • Digestive issues, like irritable bowel syndrome

  • Shortness of breath

  • Palpitations

  • Allergies or sensitivities to foods, odors, chemicals, light, or noise

Epidemiology/Pathogenesis 4, 5

  • Fatigue is a very common presenting complaint in primary care practice, however, CFS represents a very small subset of individuals who complain of chronic fatigue.

  • The exact prevalence is unknown, however the CDC estimates between 4-10 people/100,000 in the U.S. have CFS and costs the U.S. economy about $17 to $24 billion annually in medical bills and lost incomes.

  • Higher female representation (ratio about 3:1)

  • Primarily occurs in young to middle-aged adults.

  • The pathophysiology is controversial and not well understood. A number of endocrine/immunological abnormalities have been described (hypometabolic state, abnormal energy metabolism pathways, decreased serum cortisol, increased insulin-like growth factor, depressed natural killer cell function) but their causal role is unclear. A number of infectious etiologies have been proposed (Epstein-Barr virus, retroviruses, Q fever, etc.), however no infectious agent has been proven to cause CFS. Nonetheless, many patients attribute their symptoms to a viral infection.

  • Highly comorbid with mood disorders, anxiety, fibromyalgia, myofascial pain, multiple chemical hypersensitivity, thyroiditis, hypovitaminosis D, and endometriosis.

  • Risk factors: childhood trauma is associated with a 6-fold increased risk and has the highest correlation with sexual abuse, emotional abuse, and emotional neglect. Depressive and anxiety disorders are also correlated (~66% of CFS patients), however whether the depression/anxiety generally occurs before or as a consequence of CFS symptoms is controversial.

Clinical Pearls 6

  • Obtain a thorough history, a full review of systems, and a comprehensive physical/neurologic exam.

  • Differential diagnosis: the differential diagnosis is broad. From pocket psychiatry, the differential includes -> "infection (EBV, HIV, Hepatitis, Lyme), neurologic (multiple sclerosis, CVA/stroke), rheumatic (SLE, rheumatoid arthritis, Sjogrens), psychiatric (anxiety, MDD), endocrine (thyroid dysfunction, adrenal insufficiency), metabolic disturbance, sleep apnea, anemia, fibromyalgia, dehydration/orthostasis".

  • Laboratory studies: recommended initial laboratory studies in patients with chronic fatigue include complete blood count with differential count (CBC with diff), blood chemistries (including glucose, electrolytes, calcium, renal and hepatic function tests), thyroid-stimulating hormone (TSH), urinalysis (UA), and creatine kinase (CK) if muscle pain or weakness is present.

  • Other medical workup: If the history or examination suggest sleep apnea, then obtain a sleep study. If the history or exam suggest adrenal insufficiency, then evaluate for adrenal insufficiency.

Treatment 7, 8

  • General approach: many therapies have been tried for the treatment of CFS, but none are curative. Management should be supportive in nature and focus on improving function and improving common symptoms such as exercise tolerance, sleep disorders, pain, depression, anxiety, concentration, and lightheadedness.

  • Physical activity: remaining physically active is important for patients with CFS in order to maintain physical functioning and improve fatigue and other symptoms over time. Initiating and progressing through an exercise program has its challenges due to potential exacerbation of post-exertional malaise (PEM). Graded exercise therapy (GET) is a structured exercise program that aims to gradually increase how long you can carry out a physical activity, and.has been found to increase the recovery rate of CFS.

  • Psychotherapy: cognitive behavioral therapy (CBT) has also been found to decrease fatigue, improve sleep, and improve perceived general health among patients with CFS. The focus of treatment is aimed towards helping patient accept the diagnosis, feel more in control of symptoms, challenge feelings that could prevent improvement, and gain a better understanding of how their behavior can affect the condition. Sleep hygiene instructions should be discussed with all patients with CFS.

  • Pharmacologic treatment: A number of medications have been tested for the treatment of CFS. Many have been found to be of no benefit and the benefit of others is unclear, and they should be considered on a case-by-case basis in order to relieve some of the symptoms of CFS. Treatment with antidepressants should be considered in patients with comorbid depression or anxiety. Tricyclic antidepressants (TCAs) such as amitriptyline have been used to some affect in patients to improve sleep efficiency and chronic pain. Other interventions for pain include as needed nonsteroidal anti-inflammatory drug (NSAID), acetaminophen, or other nonpharmacologic interventions. In patients with CFS who have persistent dizziness and lightheadedness, there may be a role for fludrocortisone or atenolol, however this aspect is unlikely to be managed by psychiatry.


  • Next lesson we will have a review quiz and after that we will move on to our next theme: personality disorders. If you want more learning resources then check out our recommended resources page.

  • Resources for today's post include: Pocket Psychiatry and the articles referenced above.

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