Evidence-Based Reviews

2 therapies lift mood in chronic fatigue syndrome

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Usual depression and anxiety therapies may be ineffective.



Chronic fatigue syndrome (CFS) continues to puzzle and provoke. Years of research have failed to find a biomedical cause or to answer fundamental questions, such as “What is it?” and “Does it exist?”

Up to two-thirds of CFS patients have psychiatric disorders,1 but psychiatrists are not the first physicians CFS patients usually see. Primary care physicians may ask you to help confirm the diagnosis, manage patients’ anxiety and depression, differentiate CFS from somatoform disorders, or provide psychotherapy for patients and their families.

Knowing what transpires in the referring physician’s office is key to helping a patient function despite CFS. This article describes:

  • CFS clinical features and possible causes
  • psychiatric comorbidities and exclusions
  • cognitive behavioral therapy (CBT) and graded exercise, the only two therapies shown to improve CFS patients’ daily function.

Case: Anxious, depressed, and tired

Mr. A, age 43, is referred to you with anxiety and depressed mood associated with CFS, diagnosed 2 years ago. Fatigue predated Mr. A’s depression and anxiety, which his primary care physician considers consequences of CFS.

Mr. A is married, has three children, and owns a successful accounting practice. CFS was diagnosed from the classic presentation: abrupt onset of fatigue despite good health and a promising career. Now, overwhelming fatigue reduces his productivity. He makes up for frequent rest breaks by working in snatches of time, even at 4 AM. He is spending little time with his wife and children.

Defining CFS

The Centers for Disease Control and Prevention (CDC) defined CFS in 1988 while investigating infectious causes of fatigue (Table 1).2,3 Epstein-Barr virus was thought to be the cause of CFS.

Most patients who present to their primary care physicians with complaints of fatigue do not meet CDC criteria for CFS, however. These “non-CFS” patients are diagnosed as having “idiopathic chronic fatigue,” a term that is not particularly helpful because CFS remains an idiopathic disorder.

Clinical findings. As with Mr. A, many CFS patients’ fatigue begins suddenly, often with flu-like symptoms. Patients lose tolerance for exercise and alcohol and become unable to work or socialize at pre-illness levels.

Medical symptoms can overlap those of other conditions, such as fibromyalgia, chemical sensitivities, and irritable bowel disorder. These associations make the condition difficult to assess and contribute to some physicians’ difficulty in accepting CFS as a biomedical condition. Mistrust and a poor patient-physician relationship can result when the physician doubts the symptoms’ “medical” nature and the patient resents the implication that the suffering is “all in your head.”

What causes CFS? No consistent factor has been identified that explains the pathophysiology of CFS symptoms. Many possibilities have been examined, but the evidence is confusing and contradictory.

A few preliminary studies suggest possible familial (shared environmental) and genetic components, but data are sparse and no more than suggestive.4 Findings of CNS studies are inconsistent, and the search for a change in immune function or an infectious agent has been fruitless despite some patients’ infection-like symptoms. The early hypothesis that Epstein-Barr virus was responsible has been disproved.

Imaging studies, psychological testing, and neuroendocrine investigations have identified abnormalities in some patients with CFS. The most-promising findings point to abnormalities in the hypothalamic-pituitary-adrenal axis and in serotonergic neurotransmission,5 suggesting an abnormal stress response in some patients.

Table 1

CDC diagnostic criteria for chronic fatigue syndrome

At least 6 months of fatigue sufficient to “substantially reduce” patient’s level of activity
4 or more of 8 concurrent symptoms:
  • Poor memory/concentration
  • Sore throat
  • Tender glands
  • Myalgia
  • Joint pain
  • Recent-onset headache
  • Unrefreshing sleep
  • Excessive tiredness on exercise
No obvious medical or psychiatric causes, such as eating disorders, psychosis, bipolar disorder, melancholia, or substance abuse*
CDC: Centers for Disease Control and Prevention
* Many nonpsychotic psychiatric disorders (such as atypical depression) do not exclude a CFS diagnosis
Source: References 1 and 2

Case continued: Test results are normal

Mr. A has undergone extensive medical assessment (complete blood cell count; renal, hepatic, and thyroid function tests; calcium, phosphate, and glucose determinations; and urinalysis), which yielded normal results. Brain MRI findings were also normal; specifically, no evidence of multiple sclerosis.

Even so, he has had nonspecific symptoms of impaired concentration, sore throat, tender cervical nodes, muscle pain, and nonrefreshing sleep. Physical exertion can leave him drained for at least 1 or 2 days.

Psychiatric Disorders

As many as 66% of CFS patients may have one or more psychiatric comorbidities; the most common are generalized anxiety disorder, panic disorder, depression, and somatoform disorder.1 Because CFS symptoms are regarded as being not fully explained by a known medical disorder, patients are often diagnosed as having an undifferentiated somatoform disorder. Either disorder could be diagnosed in some cases, but this differentiation sheds no new light on the condition.

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