Treatment of chronic fatigue syndrome

Abstract:

Chronic Fatigue Syndrome is a disorder which is characterised by profound fatigue together with a variety of other subjective clinical features which persist over a prolonged period of time. The aetiology remains at present uncertain and therefore rational therapeutic strategies are difficult to plan. This paper reviews currently used forms of treatment aimed at correcting the possible pathophysiological mechanisms and discusses the problems associated with the management of this condition.

 

Source: McBride SJ, McCluskey DR. Treatment of chronic fatigue syndrome. Br Med Bull. 1991 Oct;47(4):895-907. http://www.ncbi.nlm.nih.gov/pubmed/1794089

 

Intravenous immunoglobulin and myalgic encephalomyelitis

Comment on: Intravenous immunoglobulins. [BMJ. 1991]

 

SIR, In his editorial on intravenous immunoglobulin Dr A D B Webster calls for multicentre trials to assess the possible efficacy of this product in various conditions including mvalgic encephalomyelitis. Two such placebo controlled trials have been completed. Unfortunately, the results are conflicting. American investigators treated their patients with 1 g/kg every month for six months. There were no obvious benefits when the treated patients were compared with controls given placebo. An Australian trial used an even higher dose of 2 g/kg over three months. Here there were significant benefits in both physical and psychological wellbeing in the treatment group.

You can read the rest of this comment here:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1670935/pdf/bmj00145-0062d.pdf

 

Source: Shepherd C. Intravenous immunoglobulin and myalgic encephalomyelitis. BMJ. 1991 Sep 21;303(6804):716. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1670935/

 

Antidepressant therapy in the chronic fatigue syndrome

Abstract:

The chronic fatigue syndrome is a condition receiving increasing recognition. Symptoms of depression are not infrequent and may be persistent and severe enough to warrant treatment. The controversy over the use of antidepressant therapy in this condition may present a dilemma for the general practitioner considering possible treatments. This paper draws on the literature and on the authors’ own observations of patients with the chronic fatigue syndrome to suggest guidelines for the use of antidepressant therapy.

Comment in:

Chronic fatigue syndrome. [Br J Gen Pract. 1991]

Chronic fatigue syndrome. [Br J Gen Pract. 1991]

 

Source: Lynch S, Seth R, Montgomery S. Antidepressant therapy in the chronic fatigue syndrome. Br J Gen Pract. 1991 Aug;41(349):339-42. http://www.ncbi.nlm.nih.gov/pubmed/1822108

Note: You can read the full article here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1371759/

 

Red blood cell magnesium and chronic fatigue syndrome

Abstract:

The hypotheses that patients with chronic fatigue syndrome (CFS) have low red blood cell magnesium and that magnesium treatment would improve the wellbeing of such patients were tested in a case-control study and a randomised, double-blind, placebo-controlled trial, respectively.

In the case-control study, 20 patients with CFS had lower red cell magnesium concentrations than did 20 healthy control subjects matched for age, sex, and social class (difference 0.1 mmol/l, 95% confidence interval [CI] 0.05 to 0.15).

In the clinical trial, 32 patients with CFS were randomly allocated either to intramuscular magnesium sulphate every week for 6 weeks (15 patients) or to placebo (17).

Patients treated with magnesium claimed to have improved energy levels, better emotional state, and less pain, as judged by changes in the Nottingham health profile. 12 of the 15 treated patients said that they had benefited from treatment, and in 7 patients energy score improved from the maximum to the minimum.

By contrast, 3 of the 17 patients on placebo said that they felt better (difference 62%, 95% CI 35 to 90), and 1 patient had a better energy score. Red cell magnesium returned to normal in all patients on magnesium but in only 1 patient on placebo. The findings show that magnesium may have a role in CFS.

Comment in:

Magnesium and chronic fatigue. [Lancet. 1991]

Magnesium and chronic fatigue syndrome. [Lancet. 1991]

Magnesium and chronic fatigue syndrome. [Lancet. 1991]

Intravenous magnesium loading in chronic fatigue syndrome. [Lancet. 1992]

 

Source: Cox IM, Campbell MJ, Dowson D. Red blood cell magnesium and chronic fatigue syndrome. Lancet. 1991 Mar 30;337(8744):757-60. http://www.ncbi.nlm.nih.gov/pubmed/1672392

 

A controlled trial of intravenous immunoglobulin G in chronic fatigue syndrome

Abstract:

PURPOSE: Currently, there is no established therapy for chronic fatigue syndrome (CFS), a recently defined illness that has been associated with a variety of immunologic abnormalities. Based on the hypothesis that a chronic viral infection or an immunoregulatory defect is involved in the pathogenesis of CFS, the therapeutic benefit of intravenous immunoglobulin G (IV IgG) was evaluated in a group of patients with CFS. Additionally, serum immunoglobulin concentrations and peripheral blood lymphocyte subset numbers were measured at the outset of the study, and the effect of IV IgG therapy on IgG subclass levels was determined.

PATIENTS AND METHODS: Thirty patients with CFS were enrolled in a double-blind, placebo-controlled trial of IV IgG. The treatment regimen consisted of IV IgG (1 g/kg) or intravenous placebo (1% albumin solution) administered every 30 days for 6 months. Participants completed a self-assessment form prior to each of the six treatments, which was used to measure severity of symptoms, functional status, and health perceptions. Patients were also asked to report adverse experiences defined as worsening of symptoms occurring within 48 hours of each treatment.

RESULTS: Twenty-eight patients completed the trial. At baseline, all 28 patients complained of moderate to severe fatigue, and measures of social functioning and health perceptions showed marked impairment. Low levels of IgG1 were found in 12 (42.9%), and 18 (64.3%) had low levels of IgG3. At the end of the study, no significant therapeutic benefit could be detected in terms of symptom amelioration or improvement in functional status, despite restoration of IgG1 levels to a normal range. Major adverse experiences were observed in 20% of both the IV IgG and placebo groups.

CONCLUSION: The results of this study indicate that IV IgG is unlikely to be of clinical benefit in CFS. In addition to the ongoing need for placebo-controlled trials of candidate therapies for CFS, an expanded research effort is needed to define the etiology and pathogenesis of this disorder.

Comment in:

Intravenous immunoglobulin treatment for the chronic fatigue syndrome. [Am J Med. 1990]

 

Source: Peterson PK, Shepard J, Macres M, Schenck C, Crosson J, Rechtman D, Lurie N. A controlled trial of intravenous immunoglobulin G in chronic fatigue syndrome. Am J Med. 1990 Nov;89(5):554-60. http://www.ncbi.nlm.nih.gov/pubmed/2239975

 

A double-blind, placebo-controlled trial of intravenous immunoglobulin therapy in patients with chronic fatigue syndrome

Abstract:

PURPOSE: The chronic fatigue syndrome (CFS) is characterized by profound fatigue, neuropsychiatric dysfunction, and frequent abnormalities in cell-mediated immunity. No effective therapy is known.

PATIENTS AND METHODS: Forty-nine patients (40 with abnormal cell-mediated immunity) participated in a randomized, double-blind, placebo-controlled trial to determine the effectiveness of high-dose intravenously administered immunoglobulin G. The patients received three intravenous infusions of a placebo solution or immunoglobulin at a dose of 2 g/kg/month. Assessment of the severity of symptoms and associated disability, both before and after treatment, was completed at detailed interviews by a physician and psychiatrist, who were unaware of the treatment status. In addition, any change in physical symptoms and functional capacity was recorded using visual analogue scales, while changes in psychologic morbidity were assessed using patient-rated indices of depression. Cell-mediated immunity was evaluated by T-cell subset analysis, delayed-type hypersensitivity skin testing, and lymphocyte transformation with phytohemagglutinin.

RESULTS: At the interview conducted by the physician 3 months after the final infusion, 10 of 23 (43%) immunoglobulin recipients and three of the 26 (12%) placebo recipients were assessed as having responded with a substantial reduction in their symptoms and recommencement of work, leisure, and social activities. The patients designated as having responded had improvement in physical, psychologic, and immunologic measures (p less than 0.01 for each).

CONCLUSION: Immunomodulatory treatment with immunoglobulin is effective in a significant number of patients with CFS, a finding that supports the concept that an immunologic disturbance may be important in the pathogenesis of this disorder.

Comment in:

Intravenous immunoglobulin treatment for the chronic fatigue syndrome. [Am J Med. 1990]

Immunoglobulin treatment for chronic fatigue syndrome. [Am J Med. 1991]

Intravenous immunoglobulin treatment of chronic fatigue syndrome. [Am J Med. 1991]

Placebo responses in patients complaining of chronic fatigue. [Am J Med. 1991]

 

Source: Lloyd A, Hickie I, Wakefield D, Boughton C, Dwyer J. A double-blind, placebo-controlled trial of intravenous immunoglobulin therapy in patients with chronic fatigue syndrome.  Am J Med. 1990 Nov;89(5):561-8. http://www.ncbi.nlm.nih.gov/pubmed/2146875

 

Post-viral fatigue syndrome, viral infections in atopic eczema, and essential fatty acids

Abstract:

Three clinical observations relating to viral infections are well-known but poorly understood. These are: the susceptibility of people with atopic eczema to viral infections; the occasional precipitation of an atopic syndrome by viral infections; the occurrence of a fatigue syndrome following viral infections.

A unifying hypothesis is presented which explains these observations in terms of the interactions between viral infections and essential fatty acid (EFA) metabolism. Key elements of the hypothesis are the facts that interferon requires 6-desaturated EFAs in order to exert its anti-viral effects, that people with atopic eczema have low levels of 6-desaturated EFAs, and that viruses, as part of their attack strategy, may reduce the ability of cells to make 6-desaturated EFAs.

The hypothesis has practical implications for the treatment of patients with viral infections.

 

Source: Horrobin DF. Post-viral fatigue syndrome, viral infections in atopic eczema, and essential fatty acids.  Med Hypotheses. 1990 Jul;32(3):211-7.  http://www.ncbi.nlm.nih.gov/pubmed/2204789

 

Liver extract-folic acid-cyanocobalamin vs placebo for chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome is a recently defined entity for which clinical criteria were proposed by the Centers for Disease Control, Atlanta, Ga. A frequently advocated treatment in Southern California is an injectable solution of bovine liver extract containing folic acid and cyanocobalamin (LEFAC).

We conducted a double-blind, placebo-controlled, crossover trial of intramuscular LEFAC in 15 patients who met the Centers for Disease Control criteria for chronic fatigue syndrome. Although patients responded to placebo and LEFAC by several criteria of functional status, no significant difference was apparent between response to placebo and that to LEFAC. The placebo response appeared to be strong.

 

Source: Kaslow JE, Rucker L, Onishi R. Liver extract-folic acid-cyanocobalamin vs placebo for chronic fatigue syndrome. Arch Intern Med. 1989 Nov;149(11):2501-3. http://www.ncbi.nlm.nih.gov/pubmed/2684076

 

Immunotherapy and enhanced antibody-dependent cell-mediated cytotoxicity using virally-infected target cells

Abstract:

We examined the ability of in vitro addition of Interleukin-2 (IL-2) to differentially enhance antibody-dependent cell mediated cytotoxicity (ADCC) utilizing cultured Epstein-Barr virus infected cells and gammaglobulin (Sandoglobulin). We found significant enhancement of ADCC when IL-2 was added. Chronic Epstein-Barr virus or Chronic Fatigue Syndrome patients in a therapeutic gammaglobulin program may benefit from IL-2 given in vivo.

 

Source: Bosse D, Ades EW. Immunotherapy and enhanced antibody-dependent cell-mediated cytotoxicity using virally-infected target cells. J Clin Lab Immunol. 1989 Jul;29(3):109-10. http://www.ncbi.nlm.nih.gov/pubmed/2561291

 

Acyclovir treatment of the chronic fatigue syndrome. Lack of efficacy in a placebo-controlled trial

Abstract:

Twenty-seven adults with a diagnosis of the chronic fatigue syndrome were enrolled in a double-blind, placebo-controlled study of acyclovir therapy. The patients had had debilitating fatigue for an average of 6.8 years, accompanied by persisting antibodies to Epstein-Barr virus early antigens (titers greater than or equal to 1:40) or undetectable levels of antibodies to Epstein-Barr virus nuclear antigens (titers less than 1:2) or both.

Each course of treatment consisted of intravenous placebo or acyclovir (500 mg per square meter of body-surface area) administered every eight hours for seven days. The same drug was then given orally for 30 days (acyclovir, 800 mg four times daily). There were six-week observation periods before, between, and after the treatments. Three patients had acyclovir-induced nephrotoxicity and were withdrawn from the study.

Of the 24 patients who completed the trial, similar numbers improved with acyclovir therapy and with placebo (11 and 10, respectively). Neither acyclovir treatment nor clinical improvement correlated with alterations in laboratory findings, including titers of antibody to Epstein-Barr virus or levels of circulating immune complexes or of leukocyte 2′,5′-oligoadenylate synthetase. Subjective improvement correlated with various measures of mood.

We conclude that acyclovir, as used in this study, does not ameliorate the chronic fatigue syndrome. We believe that the clinical improvement observed in most patients reflected either spontaneous remission of the syndrome or a placebo effect.

 

Source: Straus SE, Dale JK, Tobi M, Lawley T, Preble O, Blaese RM, Hallahan C, Henle W. Acyclovir treatment of the chronic fatigue syndrome. Lack of efficacy in a placebo-controlled trial. N Engl J Med. 1988 Dec 29;319(26):1692-8. http://www.ncbi.nlm.nih.gov/pubmed/2849717