Skip to main content
SpringerLink
Log in

Chronic Fatigue Syndrome

Probable Pathogenesis and Possible Treatments

  • Leading Article
  • Published:
Drugs Aims and scope Submit manuscript

Abstract

Chronic fatigue syndrome (CFS) belongs in the medically unexplained illnesses. It affects approximately 0.2–0.7% of the population in Western countries. It is characterised by unexplained fatigue, lasting 6 months or more, impairment of neurocognitive functions and quality of sleep, and of somatic symptoms, such as recurrent sore throat, muscle aches, arthralgias, headache and postexertional malaise. No link between infections and CFS has been clearly established but the immune system is activated, there are aberrations in several hypothalamic-pituitary axes and involvement of other parts of the central nervous system. No specific treatment has been found. Cognitive behavioural therapy is established to be of value to improve quality of life. More effective treatment should result, as advances in biomedical as well as psychological research continue.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Table I

Similar content being viewed by others

References

  1. Wessely S. Old wine in new bottles: neurasthenia and “ME”. Psychol Med 1990; 20: 35–53

    Article  PubMed  CAS  Google Scholar 

  2. Holmes GP, Kaplan JE, Gantz NM, et al. Chronic fatigue syndrome: a working case definition. Ann Intern Med 1988; 108: 387–9

    PubMed  CAS  Google Scholar 

  3. Fukuda K, Straus S, Hickie I, et al. The chronic fatigue syndrome: a comprehensive approach to its definition and study. Ann Intern Med 1994; 121: 953–9

    PubMed  CAS  Google Scholar 

  4. Wessely S. The epidemiology of chronic fatigue syndrome. Epidemiol Rev 1995; 17: 139–51

    PubMed  CAS  Google Scholar 

  5. Hagnell O, Grasbeck A, Ojesjo L, et al. Mental tiredness in the Lundby study: incidence and course over 25 years. Acta Psychiatr Scand 1993; 88: 316–21

    Article  PubMed  CAS  Google Scholar 

  6. Kroenke K, Arlington ME, Mangelsdorff AD. The prevalence of symptoms in medical outpatients and the adequacy of therapy. Arch Intern Med 1990; 150: 1685–9

    Article  PubMed  CAS  Google Scholar 

  7. Jason LA, Richman JA, Rademaker AW, et al. A community-based study of chronic fatigue syndrome. Arch Intern Med 1999; 159: 2129–37

    Article  PubMed  CAS  Google Scholar 

  8. Powell R, Dolan R, Wessely S. Attributions of self-esteem in depression and chronic fatigue syndromes. J Psychosom Res 1990: 34; 665–73

    Article  PubMed  CAS  Google Scholar 

  9. Komaroff AL. ‘Minor’ illness symptoms: the magnitude of their burden and of our ignorance. Arch Intern Med 1990; 150: 1586–7

    Article  PubMed  CAS  Google Scholar 

  10. Demitrack M, Dale JK, Straus SE, et al. Evidence for impaired activation of the hypothalamic-pituitary-adrenal axis in patients with chronic fatigue syndrome. J Clin Endocrinol Metab 1991; 73: 1224–34

    Article  PubMed  CAS  Google Scholar 

  11. Sharpe M, Clements A, Hawton K, et al. Increased prolactin response to buspirone in chronic fatigue syndrome. J Affect Disord 1996; 41: 71–6

    Article  PubMed  CAS  Google Scholar 

  12. Bakheit AMO, Behan PO, Dinan TG, et al. Possible upregulation of hypothalamic 5-hydroxytryptamine receptors in patients with postviral fatigue syndrome. BMJ 1992; 304: 1010–2

    Article  PubMed  CAS  Google Scholar 

  13. Dinan TG. Neuroendocrinology of chronic fatigue syndrome. J Chronic Fatigue Syndr 1996; 2: 69–70

    Article  Google Scholar 

  14. Joyce J, Hotopf M, Wessely S. The prognosis of chronic fatigue and chronic fatigue syndrome: a systematic review. QJM 1997; 90: 223

    Article  PubMed  CAS  Google Scholar 

  15. Straus S. History of chronic fatigue syndrome. Rev Infect Dis 1991; 13 Suppl. 1: S2

    Article  PubMed  Google Scholar 

  16. Hyams KC, Wignall FS, Roswell R. War syndromes and their evaluation: from the USCivil War to the Persian Gulf War. Ann Intern Med 1996; 125: 398–405

    PubMed  CAS  Google Scholar 

  17. Acheson ED. The clinical syndrome variously called benign myalgic encephalomyelitis, Iceland disease and epidemic neuromyasthenia. Am J Med 1959; 26: 569–5

    Article  PubMed  CAS  Google Scholar 

  18. Henderson DA, Shelokov A. Epidemic neuromyasthenia: clinical syndrome? N Engl J Med 1959; 260: 757–764, 814–8

    Article  PubMed  CAS  Google Scholar 

  19. Daugherty SA, Henry BE, Peterson DL, et al. Chronic fatigue syndrome in northern Nevada. Rev Infect Dis 1991;13 Suppl. l: S39–44

    Article  PubMed  Google Scholar 

  20. Buchwald D, Cheney PR, Peterson D, et al. A chronic illness characterized by fatigue, neurologic and immunologic disorders, and active human herpesvirus type 6 infection. Ann Intern Med 1992; 116: 103–13

    PubMed  CAS  Google Scholar 

  21. Ablashi DV, Eastman HB, Owen CB, et al. Frequent HHV-6 reactivation in multiple sclerosis (MS) and chronic fatigue syndrome (CFS) patients. J Clin Virol 2000; 3: 179–91

    Article  Google Scholar 

  22. Holmes GP, Kaplan JE, Stewart JA, et al. A cluster of patients with a chronic mononucleosis-like syndrome: is Epstein-Barr virus the cause? JAMA 1987; 257: 2297–302

    Article  PubMed  CAS  Google Scholar 

  23. Landay AL, Jessop C, Lennette ET, et al. Chronic fatigue syndrome: clinical condition associated with immune activation. Lancet 1991; 338: 707–12

    Article  PubMed  CAS  Google Scholar 

  24. Jones J. Serologic and immunologic responses in Chronic fatigue syndrome with emphasis on the Epstein-Barr Virus. Rev Infect Dis 1991; 13 Suppl. 1: S26–31

    Article  PubMed  Google Scholar 

  25. Buchwald D, Ashley RL, Pearlman T, et al. Viral serologies in patients with chronic fatigue and chronic fatigue syndrome. J Med Virol 1996; 50(1): 25–30

    Article  PubMed  CAS  Google Scholar 

  26. Mawle AC, Nisenbaum R, Dobbins JG, et al. Immune responses associated with CFS: a case control study. J Infect Dis 1997; 175(1): 136–41

    Article  PubMed  CAS  Google Scholar 

  27. Straus SE. Studies of herpesvirus infection in chronic fatigue syndrome. Ciba Found Symp Chronic Fatigue Syndrome. Chichester, UK: J Wiley & Sons, 1993; 173: 132–9

    CAS  Google Scholar 

  28. Wallace HL, Natelson B, Gause W, et al. Human herpesviruses in chronic fatigue syndrome. Clin Diagn Lab Immunol 1999; 6(2): 216–23

    PubMed  CAS  Google Scholar 

  29. Sota NE, Straus SE. CFS and herpesviruses: the fading evidence. Herpes 2000; 2: 46–50

    Google Scholar 

  30. Enbom M, Linde A, Evengård B. No evidence of active infection with human herpesvirus 6 (HHV-6) or (HHV-8) in Chronic fatigue syndrome. J Clin Microbiol 2000; 38: 2457

    PubMed  CAS  Google Scholar 

  31. Khan AS, Heneine WM, Chapman LE, et al. Assessment of a retrovirus sequence and other possible risk factors for the chronic fatigue syndrome. Ann Intern Med 1993; 118: 241–5

    PubMed  CAS  Google Scholar 

  32. Ludwig H, Bode L, Gosztonyi G. Borna disease: a persistent virus infection of the central nervous system. Prog Med Virol 1988; 35: 107–51

    PubMed  CAS  Google Scholar 

  33. Briese T, de la Torre JC, Lewis A, et al. Borna disease virus, a negative-strand RNA virus, transcribes in the nucleus of infected cells. Proc Natl Acad Sci U S A 1992; 89: 11486–9

    Article  PubMed  CAS  Google Scholar 

  34. Nakaya T, Takahashi H, Nakamura Y, et al. Demonstration of Borna disease virus RNA in peripheral blood mononuclear cells derived from Japanese patients with Chronic fatigue syndrome. FEBS Lett 1996; 378: 145–9

    Article  PubMed  CAS  Google Scholar 

  35. Kitani T, Kuratsune H, Fuke I, et al. Possible correlation between Borna disease virus infection and Japanese patients with chronic fatigue syndrome. Microbiol Immunol 1996; 40(6): 459–62

    PubMed  CAS  Google Scholar 

  36. Bode L, Komaroff AL, Ludwig H. No serologic evidence of Borna disease virus in patients with chronic fatigue syndrome. Clin Infect Dis 1992; 15: 1049

    Article  PubMed  CAS  Google Scholar 

  37. Evengård B, Briese T, Lindh G, et al. Absence of evidence of Borna disease virus infection in Swedish patients with Chronic fatigue syndrome. J Neurovirol 1999; 5: 495–9

    Article  PubMed  Google Scholar 

  38. White PD, Thomas JM, Amess J, et al. Incidence, risk and prognosis of acute and chronic fatigue syndromes and psychiatric disorders after glandular fever. Br J Psychiatry 1998; 173: 475–81

    Article  PubMed  CAS  Google Scholar 

  39. Behan PO, Behan WMH, Bell EJ. The postviral fatigue syndrome: an analysis of the findings in 50 cases. J Infect 1985; 10: 211–22

    Article  PubMed  CAS  Google Scholar 

  40. Archard LC, Bowles NE, Behan PO, et al. Postviral fatigue syndrome: persistence of enterovirus RNA in muscle and elevated creatine kinase. J R Soc Med 1988; 81: 326–9

    PubMed  CAS  Google Scholar 

  41. Yousef GE, Mann GF, Smith DG, et al. Chronic enterovirus infection in patients with postviral fatigue syndrome. Lancet 1988; I: 146–50

    Article  Google Scholar 

  42. Gow JW, Behan WMH, Simpson K, et al. Studies on enterovirus in patients with chronic fatigue syndrome. Clin Infect Dis 1993; 18 Suppl. 1: S126–32

    Article  Google Scholar 

  43. Lindh G, Samuelsson A, Hedlund Ko, et al. No findings of enteroviruses in Swedish patients with chronic fatigue syndrome. Scand J Infect Dis 1996; 28: 305–7

    Article  PubMed  CAS  Google Scholar 

  44. Swanink CMA, Melchers WJG, Van der Meer JWM, et al. Enteroviruses and the chronic fatigue syndrome. Clin Infect Dis 1994; 19: 860–4

    Article  PubMed  CAS  Google Scholar 

  45. McArdle A, McArdle F, Jacksom MJ, et al. Investigation by polymerase chain reaction of enteroviral infection in chronic fatigue syndrome. Clin Sci 1996; 90: 295–300

    PubMed  CAS  Google Scholar 

  46. Oldstone MBA, Holmstoen J, Welsh Jr RM. Alterations of acetylcholine enzymes in neuroblastoma cells persistently infected with lymphocytic choriomeningitis virus. J Cell Physiol 1977; 91: 459–72

    Article  PubMed  CAS  Google Scholar 

  47. Oldstone MBA, Sinha YN, Blount P, et al. Virus-induced alterations in homeostasis: alterations in differentiated functions of infected cells in vivo. Science 1982; 218: 1125–7

    Article  PubMed  CAS  Google Scholar 

  48. Preeyasombat C, Richards C, Silverman M, et al. Cortisol production. III. Rubella and varicella encephalopathy, with a note on their treatment with steroids. Am J Dis Child 1965; 110: 370–3

    CAS  Google Scholar 

  49. White MG, Carter NW, Rector FC, et al. Pathophysiology of epidemic St Louis encephalitis: I, Inappropriate secretion of antidiuretic hormone; II, Pituitary-adrenal function; III, Cerebral blood flow and metabolism. Ann Intern Med 1969; 71: 691–702

    PubMed  CAS  Google Scholar 

  50. Zeitoun MM, Hassan AI, Hussein ZM, et al. Adrenal glucocorticoid function in acute viral infections in children. Acta Paediatr Scand 1973; 62: 608–14

    Article  PubMed  CAS  Google Scholar 

  51. Coyle PK, Krupp LB, Doscher C, et al. Borrelia burgdorferi reactivity in patients with severe persistent fatigue who are from a region in which Lyme disease is endemic. Clin Infect Dis 1994; 18 Suppl I: S24–7

    Article  PubMed  Google Scholar 

  52. Straus SE, Fritz S, Dale JK, et al. Lymphocyte phenotype and function in the chronic fatigue syndrome. J Clin Immunol 1993; 13: 30–40

    Article  PubMed  CAS  Google Scholar 

  53. Vojdani A, Choppa PC, Tagle C, et al. Detection of Mycoplasma genus and Mycoplasma fermentans by PCR in patients with CFS. FEMS Immunol Med Microbiol 1998; 22(4): 355–65

    Article  PubMed  CAS  Google Scholar 

  54. Komaroff AL, Bell DS, Cheney PR, et al. Absence of antibody to Mycoplasma fermentans in CFS. Clin Infect Dis 1993; 6: 1074–5

    Article  Google Scholar 

  55. Komaroff AL, Wang SP, Lee J, et al. No association of chronic Chlamydia pneumoniae infection with chronic fatigue syndrome. J Infect Dis 1992; 165(1): 184

    Article  PubMed  CAS  Google Scholar 

  56. Krupp LB, Jandorf L, Coyle PK, et al. Sleep disturbance in chronic fatigue syndrome. J Psychosom Res 1993; 37(4): 325–31

    Article  PubMed  CAS  Google Scholar 

  57. Moldofsky H. Fibromyalgia, sleep disorder and chronic fatigue syndrome. Ciba Found Symp 1993; 173: 262–71

    PubMed  CAS  Google Scholar 

  58. Fischler B, Le Bon O, Hoffmann G, et al. Sleep anomalies in the chronic fatigue syndrome: a comorbidity study. Neuropsychobiology 1997; 35: 115–22

    Article  PubMed  CAS  Google Scholar 

  59. Glaser R, Kiecolt-Glaser JK. Stress-associated immune modulations relevance to viral infections and chronic fatigue syndrome. Am J Med 1998; 105: 35S–42S

    Article  PubMed  CAS  Google Scholar 

  60. Cohen S, Tyrrell DA, Smith AP. Psychological stress and susceptibility to the common cold. N Engl J Med 1991; 325: 606–12

    Article  PubMed  CAS  Google Scholar 

  61. Cleare AJ, Blair D, Chambers S, et al. Urinary free cortisol in chronic fatigue syndrome. Am J Psychiatry 2001; 158: 641–3

    Article  PubMed  CAS  Google Scholar 

  62. Scott LV, Teh J, Reznek R, et al. Small adrenal glands in chronic fatigue syndrome: a preliminary computer tomography study. Psychoneuroendocrinology 1999; 24: 759–68

    Article  PubMed  CAS  Google Scholar 

  63. Moorkens G, Berwaerts J, Wynants H, et al. Characterization of pituitary function with emphasis on GH secretion in the chronic fatigue syndrome. Clin Endocrinol 2000; 53: 99–106

    Article  CAS  Google Scholar 

  64. Kavelaars A, Kuis W, Knook L, et al. Disturbed neuroendocrine-immune interactions in chronic fatigue syndrome. J Clin Endocrinol Metab 2000; 85: 692–6

    Article  PubMed  CAS  Google Scholar 

  65. Lutgendorf SK, Antoni MH, Ironson G, et al. Physical symptoms of chronic fatigue syndrome are exacerbated by the stress of hurricane Andrew. Psychosom Med 1995; 57: 310–23

    PubMed  CAS  Google Scholar 

  66. Blalock JE. The syntax of immune-neuroendocrine communication. Immunol Today 1994; 15: 504–11

    Article  PubMed  CAS  Google Scholar 

  67. Grossman A, Costa A. The regulation of hypothalamic CRH: impact of in vitro studies on the central control of the stress response. Funct Neurol 1993; 8: 325–34

    PubMed  CAS  Google Scholar 

  68. Cope H, David AS. Neuroimaging in chronic fatigue syndrome. J Neurol Neurosurg Psychiatry 1996; 60: 471–3

    Article  PubMed  CAS  Google Scholar 

  69. Schwartz RB, Komaroff AL, Garada BM, etal. SPECT imaging of the brain: comparison of findings in patients with chronic fatigue syndrome, AIDS dementia complex and major unipolar depression. AJR Am J Roentgenol 1994; 162: 943–51

    PubMed  CAS  Google Scholar 

  70. Costa DC, Tannock C, Brostoff J. Brainstem perfusion is impaired in chronic fatigue syndrome. QJM 1995; 88: 767–73

    PubMed  CAS  Google Scholar 

  71. Lange G, Holodny AI, DeLuca J, et al. Quantitative assessent of cerebral ventricular volumes in chronic fatigue syndrome. Appl Neuropsychol 2001; 8: 23–30

    Article  PubMed  CAS  Google Scholar 

  72. Cook DB, Lange G, De Luca J, et al. Relationship of brain MRI abnormalities and physical functional status in chronic fatigue syndrome. Int J Neurosci 2001; 107: 1–6

    Article  PubMed  CAS  Google Scholar 

  73. Kuratsune H, Yamaguti K, Lindh G, et al. Brain regions involved in fatigue sensation: reduced acetylcarnitine uptake into the brain. Neuroimage 2002; In press

  74. Abbey SE, Garfinkel PE. Chronic fatigue syndrome and depression: cause, effect, or covariate. Rev Infect Dis 1991; 13 Suppl. 1: 73–83

    Article  Google Scholar 

  75. Johnson SK, DeLuca J, Fiedler N, et al. Cognitive functioning of patients with chronic fatigue syndrome. Clin Infect Dis 1994; 18 Suppl. 1: S84–5

    Article  PubMed  Google Scholar 

  76. Marcel B, Komaroff AL, Fagioli LR, et al. Cognitive deficits in patients with chronic fatigue syndrome. Biol Psychiatry 1996; 40(6): 535–41

    Article  PubMed  CAS  Google Scholar 

  77. Michiels V, Cluydts R, Fischler B, et al. Cognitive functioning in patients with chronic fatigue syndrome. J Clin Exp Neuropsychol 1996; 18(5): 666–77

    Article  PubMed  CAS  Google Scholar 

  78. DeLuca J, Johnson SK, Ellis SP, et al. Cognitive functioning is impaired in patients with chronic fatigue syndrome devoid of psychiatric disease. J Neurol Neurosurg Psychiatry 1995; 62(2): 151–5

    Article  Google Scholar 

  79. DeLuca J, Johnson SK, Ellis SP, et al. Sudden vs gradual onset of chronic fatigue syndrome differentiates individuals on cognitive and psychiatric measures. J Psychiatr Res 1997; 31(1): 83–90

    Article  PubMed  CAS  Google Scholar 

  80. Tiersky LA, Johnson SK, Lange G, et al. Neuropsychology of chronic fatigue syndrome: a critical review. J Clin Exp Neuropsychol 1997; 19(4): 560–86

    Article  PubMed  CAS  Google Scholar 

  81. DeLuca J, Johnson SK, Beldowicz D, et al. Neuropsychological impairments in chronic fatigue syndrome, multiple sclerosis, and depression. J Neurol Neurosurg Psychiatry 1995; 58(1): 38–43

    Article  PubMed  CAS  Google Scholar 

  82. Klimas NG, Salvato FR, Morgan R, et al. Immunologic abnormalities in chronic fatigue syndrome. J Clin Microbiol 1990; 28: 1403–10

    PubMed  CAS  Google Scholar 

  83. Levy JA. Viral studies of chronic fatigue syndrome. Clin Infect Dis 1994; 18: 117–20

    Article  Google Scholar 

  84. Tirelli U, Bernaardi D, Improta S, et al. Immunologic abnormalities in CFS. J Chronic Fatigue Syndr 1996; 2(1): 8596

    Article  Google Scholar 

  85. Patarca R, Klimas N, Sandier D, et al. Interindividual immune status variation patterns in patients with chronic fatigue syndrome: association with gender and tumor necrosis factor system. J Chronic Fatigue Syndr 1996; 2(1): 7–41

    Google Scholar 

  86. Gupta S, Vayuvegula B. A comprehensive immunological analysis in chronic fatigue syndrome. Scand J Immunol 1991; 3: 319–27

    Article  Google Scholar 

  87. Caligiuri M, Murray C, Buchwald D, et al. Phenotypic and functional deficiency of natural killer cells in patients with chronic fatigue syndrome. J Immunol 1987; 139: 3306–13

    PubMed  CAS  Google Scholar 

  88. Chao CC, Janoff EN, Hu SX, et al. Altered cytokine release in peripheral blood mononuclear cell cultures from patients with the chronic fatigue syndrome. Cytokine 1991; 3: 292–8

    Article  PubMed  CAS  Google Scholar 

  89. Morrison LJA, Behan WHM, Behan PO. Changes in natural killer cell phenotype in patients with post-viral fatigue syndrome. Clin Exp Immunol 1991; 83: 441–6

    Article  PubMed  CAS  Google Scholar 

  90. Fletcher MA, Maher K, Klimas NG. Natural killer cell function in chronic fatigue syndrome. Clin Appl Immuno Rev 2002; 2: 129–39

    Article  Google Scholar 

  91. Maher K, Klimas N, Fletcher MA. Flow cytometric measurements of perform and natural killer cell activity [abstract 47]. Proceedings of the AACFS meeting. 2001 Jan 26–29; Seattle (WA)

  92. Lloyd A, Hickie I, Hickie C, et al. Cell-mediated immunity in patients with chronic fatigue syndrome, healthy control subjects and patients with major depression. Clin Exp Immunol 1992; 87: 76–9

    Article  PubMed  CAS  Google Scholar 

  93. Bennett AL, Chao CC, Hu S, et al. Elevation of bioactive transforming growth factor-beta in serum from patients with chronic fatigue syndrome. J Clin Immunol 1997; 17: 160–6

    Article  PubMed  CAS  Google Scholar 

  94. Chao CC, Gallagher M, Phair J, et al. Serum neoptrin and interleukin-6 levels in chronic fatigue syndrome. J Infect Dis 1990; 162: 1412–3

    Article  PubMed  CAS  Google Scholar 

  95. Linde A, Andersson B, Svenson SB, et al. Serum levels of lymphokines and soluble cellular receptors in primary Epstein-Barr virus infection and in patients with chronic fatigue syndrome. J Infect Dis 1992; 165: 994–1000

    Article  PubMed  CAS  Google Scholar 

  96. Gupta S, Aggarwal S, Starr A. Increased production of interleukin-6 by adherent and non-adherent mononuclear cells during “natural fatigue” but not following “experimental fatigue” in patients with chronic fatigue syndrome. Int J Mol Med 1999; 3(2): 209–13

    PubMed  CAS  Google Scholar 

  97. Cannon JG, Angel JB, Abad LW, et al. Interleukin-1 beta, interleukin-1 receptor antagonist, and soluble interleukin-1 receptor type II secretion in chronic fatigue syndrome. J Clin Immunol 1997; 17: 253–61

    Article  PubMed  CAS  Google Scholar 

  98. Suhaldonik RJ, Reichenbach NL, Hitzges P, et al. Upregulation of the 2-5A synthetase/RNase L antiviral pathway associated with chronic fatigue syndrome. Clin Infect Dis 1994; 18 Suppl. 1: S96–S104

    Article  Google Scholar 

  99. Suhaldonik RJ, Peterson DL, O Brien K, et al. Biochemical evidence for a novel low molecular weight 2-5A-dependent RNase L in chronic fatigue syndrome. J Interferon Cytokine Res 1997; 17: 377–85

    Article  Google Scholar 

  100. Moldofsky H. Sleep, neuroimmune and neuroendocrine functions in fibromyalgia and chronic fatigue syndrome. Adv Neuroimmunol 1995; 5(1): 39–56

    Article  PubMed  CAS  Google Scholar 

  101. Cacioppo JT, Berntson GG, Malarkey WB, et al. Autonomic, neuroendocrine, and immune responses to psychological stress: the reactivity hypothesis. Ann N Y Acad Sci 1998; 840: 664–73

    Article  PubMed  CAS  Google Scholar 

  102. Yang EV, Glaser R. Stress-induced immunomodulation: impact on immune defenses against infectious disease. Biomed Pharmacother 2000; 54: 245–50

    Article  PubMed  CAS  Google Scholar 

  103. Kiecolt-Glaser JK, Glaser R. Psychoneuroimmunology and health consequences: data and shared mechansims. Psychosom Med 1995; 57: 269–74

    PubMed  CAS  Google Scholar 

  104. Whiting P, Bagnall AM, Sowden AJ, et al. Interventions for the treatment and mangaement of chronic fatigue syndrome: a systematic review. JAMA 2001; 286: 1360–8

    Article  PubMed  CAS  Google Scholar 

  105. Straus SE, Dale JK, Tobi M, et al. Acyclovir treatment of the chronic fatigue syndrome: lack of efficacy in a placebo-controlled trial. N Engl J Med 1988; 3119: 1692–8

    Article  Google Scholar 

  106. Lloyd A, Hickie I, Wakefield D, et al. A double-blind, placebo-controlled trial of intravenous immunoglobulin therapy in patients with the chronic fatigue syndrome. Am J Med 1990; 89: 561–8

    Article  PubMed  CAS  Google Scholar 

  107. Vollmer-Conna U, Hickie I, Hadzi-Pavlovic D, et al. Intravenous immunoglobulin is ineffective in the treatment of patients with chronic fatigue syndrome. Am J Med 1997; 103: 38–43

    Article  PubMed  CAS  Google Scholar 

  108. Peterson PK, Shepard J, Macres M, et al. A controlled trial of intravenous immunoglobulin in chronic fatigue syndrome. Am J Med 1990; 89: 554–60

    Article  PubMed  CAS  Google Scholar 

  109. See DM, Tilles JG. Alpha-interferon treatment of patients with chronic fatigue syndrome. Immunol Invest 1996; 25: 153–64

    Article  PubMed  CAS  Google Scholar 

  110. Brook MG, Bannister BA, Weir WR. Interferon-alpha therapy for patients with chronic fatigue syndrome. J Infect Dis 1993; 168: 791–2

    Article  PubMed  CAS  Google Scholar 

  111. De Vinci C, Levine PH, Pizza G, et al. Lessons from a pilot study of transfer factor in chronic fatigue syndrome. Biotherapy 1996; 9: 87–90

    Article  PubMed  Google Scholar 

  112. Andersson M, Bagby JR, Dyrehag LE, et al. Effects of staphylococcus toxoid vaccine on pain and fatigue in patients with fibromyalgia / chronic fatigue syndrome. Eur J Pain 1998; 2: 133–42

    Article  PubMed  Google Scholar 

  113. Strayer DR, Carter WA, Brodsky I, et al. A controlled clinical trial with a specifically configured RNA drug, poly(I)-poly(C12U), in chronic fatigue syndrome. Clin Infect Dis 1994 Jan; 18 Suppl. 1: S88–95

    Article  PubMed  Google Scholar 

  114. Klimas NG, Walling J, Smith M, et al. Experimental therapy results in clinical and immunologic improvement in chronic fatigue syndrome (CFS) patients [abstract 48]. AACFS meeting 2001 Jan 28–29; Seattle (WA)

  115. McKenzie R, O Fallon A, Dale J, et al. Low-dose hydrocortisone for treatment of chronic fatigue syndrome: a randomized controlled trial. JAMA 1998; 280: 1061–6

    Article  PubMed  CAS  Google Scholar 

  116. Cleare AJ, Heap E, Malhi GS, et al. Low-does hydrocortisone in chronic fatigue syndrome: a randomised crossover trial. Lancet 1999; 353: 455–8

    Article  PubMed  CAS  Google Scholar 

  117. Peterson PK, Pheley A, Schroeppel J, et al. A preliminary placebo-controlled crossover trial of fludrocortisone for chronic fatigue syndrome. Arch Intern Med 1998; 158: 908–14

    Article  PubMed  CAS  Google Scholar 

  118. Rowe PC, Calkins H, DeBusk K, et al. Fludrocortisone acetate to treat nerually mediated hypotension in chronic fatigue syndrome: a randomized controlled trial. JAMA 2001; 285: 52–9

    Article  PubMed  CAS  Google Scholar 

  119. Moorkens G, Wynants H, Abs R. Effect of growth hormone treatment in patients with chronic fatigue synrome: a preliminary study. Growth Horm IGF Res 1998; 8: 131–3

    Article  PubMed  CAS  Google Scholar 

  120. Snorrason E, Geirsson A, Stefansson K. Trial of a selective acetylcholinesterase inhibitor galanthamine hydrobromide, in the treatment of chronic fatigue syndrome. J Chronic Fatigue Syndr 1996; 2: 35–54

    Article  Google Scholar 

  121. Forsyth LM, Preuss HG, MacDowell AL, et al. Therapeutic effects of oral NADH on the symptoms of patients with chronic fatigue syndrome. Ann Allergy Asthma Immunol 1999; 82: 185–91

    Article  PubMed  CAS  Google Scholar 

  122. Steinberg P, McNutt BE, Marshall P, et al. Double-blind placebo-controlled study of the efficacy of oral terfenadine in the treatment of chronic fatigue syndrome. J Allergy Clin Immunol 1996; 97 (1 Pt 1): 119–26

    Article  PubMed  CAS  Google Scholar 

  123. Natelson BH, Cheu J, Pareja J, et al. Randomized, double blind, controlled placebo-phase in trial of low dose phenelzine in the chronic fatigue syndrome. Psychopharmacology (Berl) 1996; 124: 226–30

    Article  CAS  Google Scholar 

  124. Vercoulen JH, Swanink CM, Zitman FG, et al. Randomized, double-blind, placebo-controlled study of fluoxetine in chronic fatigue syndrome. Lancet 1996; 347: 858–61

    Article  PubMed  CAS  Google Scholar 

  125. Wearden AJ, Morriss RK, Mullis R, et al. Randomised, double-blind, placebo-controlled treatment trial of fluoxetine and graded exercise for chronic fatigue syndrome. Br J Psychiatry 1998; 172: 485–90

    Article  PubMed  CAS  Google Scholar 

  126. Natelson BH, Cheu J, Hill N, et al. Single-blind, placebo phase-in trial of two escalating doses of selegiline in the chronic fatigue syndrome. Neuropsychobiology 1998; 172: 485–90

    Google Scholar 

  127. Hickie IB, Wilson AJ, Wright JM, et al. A randomized double-blind placebo-controlled trial of moclobemide in patients with chronic fatigue syndrome. J Clin Psychiatry 2000; 61: 643–8

    Article  PubMed  CAS  Google Scholar 

  128. Fulcher KY, White PD. Randomised controlled trial of graded exercise in patients with the chronic fatigue syndrome. BMJ 1997; 314: 1647–52

    Article  PubMed  CAS  Google Scholar 

  129. Field TM, Sunshine W, Hernandez-Reif M, et al. Massage therapy effects on depression and somatic symptoms in chronic fatigue syndrome. J Chronic Fatigue Syndr 1997; 3: 43–51

    Article  Google Scholar 

  130. Cox IM, Campbell MJ, Dowson D. Red blood cell magnesium and chronic fatigue syndrome. Lancet 1991; 337: 757–60

    Article  PubMed  CAS  Google Scholar 

  131. Warren G, McKendrick M, Peet M. The role of essential fatty acids in chronic fatigue syndrome: a case-controlled study of red cell membrane essential fatty acids (EFA) and a placebo-controlled treatment study with high dose of EFA. Acta Neurol Scand 1999; 99: 112–6

    Article  PubMed  CAS  Google Scholar 

  132. Behan PO, Behan WM, Horrobin D. Effect of high doses of essential fatty acids on the postviral fatigue syndrome. Acta Neurol Scand 1990; 82: 209–16

    Article  PubMed  CAS  Google Scholar 

  133. Kaslow JE, Rucker L, Onishi R. Liver extract-folic acid-cyanocobolamin vs placebo for chronic fatigue syndrome. Arch Intern Med 1989; 149: 2501–3

    Article  PubMed  CAS  Google Scholar 

  134. Lloyd AR, Hickie I, Brockman A, et al. Immunologic and psychologic therapy for patients with chronic fatigue syndrome: a double-blind, placebo-controlled trial. Am J Med 1993; 94: 197–203

    Article  PubMed  CAS  Google Scholar 

  135. Sharpe M, Hawton K, Simkin S, et al. Cognitive behaviour therapy for the chronic fatigue syndrome: a randomized controlled trial. BMJ 1996; 312: 22–6

    Article  PubMed  CAS  Google Scholar 

  136. Deale A, Chalder T, Marks I, et al. Cognitive behavior therapy for chronic fatigue syndrome: a randomized controlled trial. Am J Psychiatry 1997; 153: 408–14

    Google Scholar 

  137. Deale A, Husain K, Chalder T, et al. Long-term outcome of cognitive behavior therapy versus relaxation therapy for chronic fatigue syndrome: a 5-year follow-up study. Am J Psychiatry 2001; 158: 2038–42

    Article  PubMed  CAS  Google Scholar 

  138. Prins JB, Bleijenberg G, Bazelmans E, et al. Cognitive behaviour therapy for chronic fatigue syndrome: a multicentre randomised controlled trial. Lancet 2001; 357: 841–7

    Article  PubMed  CAS  Google Scholar 

  139. Ax S, Gregg VH, Jones D. Chronic fatigue syndrome: sufferer s evaluation of medical support. J R Soc Med 1997; 90: 250–4

    PubMed  CAS  Google Scholar 

  140. Reeves B. CDC and prevention planning session for optimizing the CFS case definition: practical applications, methodology. AACFS meeting 2001 Jan 28–29; Seattle (WA)

  141. Sharpe M, Chalder T, Palmer I, et al. Chronic fatigue syndrome: a practical guide to assessment and management. Gen Hosp Psychiatry 1997; 19: 185–99

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

No sources of funding were used to assist in the preparation of this manuscript. The authors have no conflicts of interest that are directly relevant to the content of this manuscript.

Author information

Authors and Affiliations

  1. Department of Immunology, Microbiology and Pathology F82, Karolinska Institutet at Huddinge University Hospital, SE-14186, Stockholm, Sweden

    Birgitta Evengård

  2. Department of Medicine, University of Miami School of Medicine and Miami VAMC, Miami, Florida, USA

    Nancy Klimas

Authors
  1. Birgitta Evengård
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nancy Klimas
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Birgitta Evengård.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Evengård, B., Klimas, N. Chronic Fatigue Syndrome. Drugs 62, 2433–2446 (2002). https://doi.org/10.2165/00003495-200262170-00003

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003495-200262170-00003

Keywords

Search

Navigation