Addressing Depression in Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome

chronic fatigue
chronic fatigue
Clinicians address issues relating to treating patients with comorbid chronic fatigue syndrome and mood disorders.

Anxiety and mood disorders, especially major depressive disorder (MDD), are highly prevalent in patients with the condition known as chronic fatigue syndrome or myalgic encephalomyelitis (ME/CFS), also sometimes called Chronic Fatigue Immune Dysfunction (CFIDS) or Systemic Exertion Intolerance Disease (SEID).1 The reason for the high prevalence of depression in patients with ME/CFS has not yet been fully explained, and the topic remains a subject of debate among researchers, patients, and patient advocates.2

Although the true prevalence of ME/CFS is difficult to ascertain because of the varied methods of assessment, a meta-analysis of 14 studies estimated it at 3.28% on the basis of patient self-reports.3 ME/CFS is characterized by persistent and disabling fatigue of at least 6 months’ duration that is not alleviated by rest, and which may worsen with mental or physical exertion. At this time, most diagnostic criteria state that patients should not be diagnosed with ME/CFS in the presence of an identified medical or psychiatric cause for fatigue. Laboratory markers are presently not available to confirm the diagnosis of ME/CFS or point to optimal treatments.4

In an email interview, Susan K. Johnson, PhD, professor of psychological science, University of North Carolina, Charlotte, told Psychiatry Advisor that prevalence estimates of depression in patients with ME/CFS span a wide range, from a low of 5% to as high as 80%. “This wide range is likely due to the coding assumptions applied to psychiatric interviews. It is possible to overestimate the prevalence of psychiatric disorders in CFS when there are so many overlapping symptoms that, depending on coding assumptions, can be attributed to somatic or psychiatric causes.” Persistent fatigue, painful physical symptoms, sleep disturbances, poor concentration, psychomotor retardation, and decreased libido are characteristic features of both MDD and ME/CFS.5

Dr Johnson noted that there are distinguishing factors that differentiate the depression seen in CFS from clinical depression. “Whereas depressed patients’ cognitions are dominated by a negative view of the self, CFS patients are primarily preoccupied with symptoms for which they make somatic attributions. People with CFS [are] generally more disabled than depressed patients. While exercise exacerbates fatigue in CFS, individuals with depression generally report more positive mood following exercise. Additionally, CFS can be separated from depression in terms of neuroimaging and neuroendocrine responses.”

Some researchers believe that depression, fatigue, and other manifestations of MD/CFS are part of the symptom cluster of an underlying biological disease state, possibly involving the presence of a hypometabolic syndrome, disturbances in the hypothalamic-pituitary-adrenal axis, activation of the shared oxidative and nitrosative pathway, or aberrations in the 2-5A synthetase/RNase L pathways.6,7

Other researchers contend that CE/MDD is an atypical manifestation of anxiety or depressive states, and that it is best understood as a psychological disorder. Still others believe that the depression common in patients with ME/CFS is a natural response to the severe fatigue and disability imposed by the disease process.6

Related Articles

Eric Gordon, MD, a physician whose California-based practice focuses on complex chronic illnesses, told Psychiatry Advisor that depression should not be regarded as an integral feature of CFS. “There are CFS patients who also have depression. Depression is often an example of the inflammatory response in certain people’s central nervous system, and since inflammation may be part of CFS, we see this type of depression in some patients with CFIDS. Patients with CFS may have an element of situational depression because their lives are interrupted and their friends and family may treat them as malingerers; however, this is not in any way a defining characteristic of CFIDS patients. Many are not any more depressed than anyone else with a chronic disease.”

The biopsychosocial model of CFS, endorsed by a number of researchers in the field, conceptualizes CFS as a multidimensional experience in which both physiological and psychological factors combine to precipitate and perpetuate the illness.8-10 Dr Johnson noted that many people with ME/CFS have objections to the biopsychosocial model, as it may imply that the syndrome is primarily a result of psychosocial factors instead of an underlying pathobiological process. “The [biopsychosocial] model is generally associated with cognitive behavioral therapy and graded exercise approaches. People who have a very strong physiological/medical view of their illness etiology can find this approach dismissive of their illness experience. Some also argue that graded exercise can be harmful because exercise intolerance is a hallmark of the disease.” Graded exercise therapy, which involves a gradual increase of physical activity over time, is intended to address the presumed deconditioning effects of CFS, whereas cognitive behavioral therapy is meant to challenge patients’ purported fears of exertion, maladaptive illness beliefs, and overfocus on symptoms.10,11

Dr Johnson told Psychiatry Advisor that people with CFS are unlikely to seek help from mental health professionals. “Community studies of CFS find that while many people endorse depression symptoms, they tend to seek help from physicians for these symptoms. Patients who are seeking treatment from a mental health provider will likely be more open to CBT approaches which have been shown to be helpful. CBT requires that the patient be willing to examine and change their beliefs about the illness and its disability. Antidepressants are not very helpful in CFS, although they offer symptomatic relief in some cases. For many patients with CFS, challenging their illness beliefs (via CBT) will be counterproductive, and ACT (acceptance and commitment therapy) and stress management approaches may be more helpful. Approaches to treatment need to be individualized and respectful of the patients’ lived experience.”


  1. Janssens KAM, Zijlema WL, Joustra ML, Rosmalen JGM. Mood and anxiety disorders in chronic fatigue syndrome, fibromyalgia, and irritable bowel syndrome: Results from the LifeLines Cohort Study. Psychosom Med. 2015;77(4):449.
  2. Larkin D, Martin CR. The interface between chronic fatigue syndrome and depression: A psychobiological and neurophysiological conundrum. Neurophysiol Clin Neurophysiol. 2017;47(2):123-129.
  3. Johnston S, Brenu EW, Staines D, Marshall-Gradisnik S. The prevalence of chronic fatigue syndrome/myalgic encephalomyelitis: a meta-analysis. Clin Epidemiol. 2013;5:105-110.
  4. Christley Y, Duffy T, Martin CR. A review of the definitional criteria for chronic fatigue syndrome. J Eval Clin Pract. 2012;18(1):25-31.
  5. Bair MJ, Robinson RL, Katon W, Kroenke K. Depression and pain comorbidity: a literature review. Arch Intern Med. 2003;163(20):2433-2445.
  6. Christley Y, Duffy T, Everall IP, Martin CR. The neuropsychiatric and neuropsychological features of chronic fatigue syndrome: revisiting the enigma. Curr Psychiatry Rep. 2013;15(4):353.
  7. Naviaux RK, Naviaux JC, Li K, et al. Metabolic features of chronic fatigue syndrome. Proc Natl Acad Sci U S A. 2016;113(37):E5472-E5480.
  8. Afari N, Buchwald D. Chronic fatigue syndrome: a review. Am J Psychiatry. 2003;160(2):221-236.
  9. Geraghty KJ, Esmail A. Chronic fatigue syndrome: is the biopsychosocial model responsible for patient dissatisfaction and harm?Br J Gen Pract J R Coll Gen Pract. 2016;66(649):437-438.
  10. Johnson SK. Chronic fatigue syndrome: a biopsychosocial perspective. In: Friedman HS, ed. Encyclopedia of Mental Health (Second Edition). Oxford: Academic Press; 2016:279-283.
  11. Wilshire CE, Kindlon T, Courtney R, et al. Rethinking the treatment of chronic fatigue syndrome—a reanalysis and evaluation of findings from a recent major trial of graded exercise and CBT. BMC Psychol. 2018;6:6.