Treatment of the chronic fatigue syndrome. A review and practical guide

Abstract:

The chronic fatigue syndrome (CFS) was formally defined in 1988 to describe a syndrome of severe and disabling fatigue of uncertain aetiology associated with a variable number of somatic and/or psychological symptoms. CFS has been reported in most industrialised countries and is most prevalent in women aged between 20 and 50 years.

Despite occasional claims to the contrary, the aetiology of CFS remains elusive. Although abnormalities in tests of immune function and cerebral imaging have been described in variable numbers of CFS patients, such findings have been inconsistent and cannot be relied upon, either to establish or exclude the diagnosis. Thus, diagnosis rests on fulfillment of the Centers for Disease Control case definition which was revised in 1992. This case definition remains somewhat controversial, largely due to its subjectiveness.

The mainstay of treatment is establishing the diagnosis and educating the patient about the illness. An empathetic clinician can stop further consultations elsewhere (‘doctor shopping’) and subsequent excessive investigations, which frequently occur in such patients.

Most patients should undertake a trial of antidepressant therapy, even if major depression is not present. The choice of antidepressant drug should tailor the tolerability profile to relief of particular CFS symptoms, such as insomnia or hypersomnia. Failure to improve within 12 weeks warrants an alternative antidepressant agent of another class. Many other drugs have been reported anecdotally to be beneficial, but no therapy has been demonstrated to be reproducibly useful in double-blind, placebo-controlled clinical trials with an adequate duration of follow-up.

 

Source: Blondel-Hill E, Shafran SD. Treatment of the chronic fatigue syndrome. A review and practical guide. Drugs. 1993 Oct;46(4):639-51. http://www.ncbi.nlm.nih.gov/pubmed/7506650

 

Disagreeing on how to treat CFS patients

Comment on: Chronic fatigue syndrome. A fresh look at an old problem. [Can Fam Physician. 1993]

 

There are some unfortunate inaccuracies in the article “Chronic Fatigue Syndrome.”‘ While the general information is useful in a very basic sense, two of the so-called “fresh look” items are inaccurate and misleading.

First, Dr McSherry suggests that “Oral magnesium supplements are indicated for CFS patients with subnormal red blood cell magnesium levels….” Presumably this recommendation comes from Dr McSherry’s reference to the study done by Cox et al. In this paper, red blood cell magnesium levels were found to be lower in patients diagnosed with chronic fatigue syndrome (CFS) than in a matched normal group, and patients were found to improve with intramuscular injections of 50% magnesium sulphate (1 g in 2 mL) every week for 6 weeks. However, oral magnesium has not been tested for its effectiveness in patients with CFS. Dr McSherry’s recommendation to use oral magnesium is, therefore, inaccurate and misleading.

You can read the rest of this comment here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2379656/pdf/canfamphys00111-0026b.pdf

 

Source: Leyton E. Disagreeing on how to treat CFS patients. Can Fam Physician. 1993 May;39:1022-4. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2379656/

 

Immunologic and psychologic therapy for patients with chronic fatigue syndrome: a double-blind, placebo-controlled trial

Abstract:

PURPOSE: To evaluate the potential benefit of immunologic therapy with dialyzable leukocyte extract and psychologic treatment in the form of cognitive-behavioral therapy (CBT) in patients with chronic fatigue syndrome (CFS).

PATIENTS AND METHODS: Immunologic and psychologic treatments were administered to 90 adult patients who fulfilled diagnostic criteria for CFS in a double-blind, randomized, and placebo-controlled study. A four-cell trial design allowed the assessment of benefit from immunologic and psychologic treatment individually or in combination. Outcome was evaluated by measurement of global well-being (visual analogue scales), physical capacity (standardized diaries of daily activities), functional status (Karnofsky performance scale), and psychologic morbidity (Profile of Mood States questionnaire), and cell-mediated immunity was evaluated by peripheral blood T-cell subset analysis and delayed-type hypersensitivity skin testing.

RESULTS: Neither dialyzable leukocyte extract nor CBT (alone or in combination) provided greater benefit than the nonspecific treatment regimens.

CONCLUSIONS: In this study, patients with CFS did not demonstrate a specific response to immunologic and/or psychologic therapy. The improvement recorded in the group as a whole may reflect both nonspecific treatment effects and a propensity to remission in the natural history of this disorder.

Comment in:

Treatment for chronic fatigue syndrome. [Am J Med. 1994]

Cognitive behavior therapy for chronic fatigue syndrome. [Am J Med. 1995]

Cognitive behavior therapy for chronic fatigue syndrome. [Am J Med. 1995]

 

Source: Lloyd AR, Hickie I, Brockman A, Hickie C, Wilson A, Dwyer J, Wakefield D. Immunologic and psychologic therapy for patients with chronic fatigue syndrome: a double-blind, placebo-controlled trial. Am J Med. 1993 Feb;94(2):197-203. http://www.ncbi.nlm.nih.gov/pubmed/8430715

 

Chronic fatigue syndrome and the treatment process

Abstract:

Fatigue is a common complaint in general practice and is often associated with psychiatric and psychosocial problems and demoralization. Although the Centers for Disease Control definition of chronic fatigue syndrome (CFS) excludes pre-existing psychiatric illness, common psychosocial problems short of a clinical disorder (such as irritability, difficulty in thinking, inability to concentrate, depression and sleep disturbance) overlap with the criteria for CFS.

Psychological states can affect the course of CFS or become confused in the patient’s and doctor’s mind with the course of infection. The core dilemma in practice is how aggressively to pursue a possible basis for CFS when it persists in the absence of an identifiable external cause. Possibilities for exploration are numerous and potentially expensive. In practice, the persistence of doctors depends on the patient’s illness behaviour, on financial and organizational factors, and on the culture of medical care and practice styles.

It is essential to differentiate the appropriate management of CFS from scientific study where intensive investigation may be warranted. In practice doctors should proceed in a manner that conveys concern, supports function, and avoids dysfunctional illness behaviour and inadvertent legitimization and reinforcement of disability.

 

Source: Mechanic D. Chronic fatigue syndrome and the treatment process. Ciba Found Symp. 1993;173:318-27; discussion 327-41. http://www.ncbi.nlm.nih.gov/pubmed/8491105

 

Pharmacological approaches to the therapy of chronic fatigue syndrome

Abstract:

Although a variety of pharmacological agents have been used to treat patients with chronic fatigue syndrome none has been shown to effect a complete resolution of symptoms.

Data obtained from a retrospective study and from an objective assessment of the aerobic work capacity of patients with this disorder suggest that the underlying pathophysiological abnormality is a disorder of sleep regulation. This results not only in profound fatigue and lethargy but also reduced sensory threshold for pain, disordered temperature regulation, cardiovascular abnormalities, disturbed higher cerebral function and mental depression.

Drugs which modulate sleep, such as tricyclic antidepressants, have a limited effect in improving the symptoms that CFS patients experience. We suggest that other agents which affect central nervous system neurotransmitters, particularly serotonin, may have potential in the management of this condition and need to be evaluated in large controlled clinical trials.

 

Source: McCluskey DR. Pharmacological approaches to the therapy of chronic fatigue syndrome. Ciba Found Symp. 1993;173:280-7; discussion 287-97. http://www.ncbi.nlm.nih.gov/pubmed/8491103

 

Psychotropic treatment of chronic fatigue syndrome and related disorders

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) and fibromyalgia frequently are associated with symptoms of major depression. For this reason, antidepressants have been used in treatment of these disorders; however, little direction has been provided into this application in psychopharmacology.

METHOD: First, nine studies were reviewed regarding the relationship of the symptoms of fatigue and depression. Next, 23 reports (12 double-blind studies, 7 open studies, and 4 case reports) were reviewed for the effectiveness of therapy as assessed by global response and improvement of both depression and pain. Studies were differentiated by type of controls, as well as by alleged mechanism of action of the pharmacologic agent.

RESULTS: Disturbances in brain neurochemistry shared by CFS and major depression may serve as a basis for the effectiveness of some antidepressants in CFS. Response to some antidepressants in patients with CFS or fibromyalgia may occur at doses lower than those used in major depression, e.g., amitriptyline 25-75 mg/day. We further found that the more serotonergic treatments (e.g., clomipramine) were more successful in alleviating pain than depression, whereas catecholaminergic agents (e.g., maprotiline, bupropion) seemed particularly effective for symptoms of associated depression.

CONCLUSION: To maximize response of the physiologic and psychological consequences of the disorder, more investigation is needed to replicate the apparent findings that relate the neurochemical impairment underlying CFS and fibromyalgia to the type of antidepressant mechanism.

 

Source: Goodnick PJ, Sandoval R. Psychotropic treatment of chronic fatigue syndrome and related disorders. J Clin Psychiatry. 1993 Jan;54(1):13-20. http://www.ncbi.nlm.nih.gov/pubmed/8428892

 

Isolated diastolic dysfunction of the myocardium and its response to CoQ10 treatment

Abstract:

Symptoms of fatigue and activity impairment, atypical precordial pain, and cardiac arrhythmia frequently precede by years the development of congestive heart failure.

Of 115 patients with these symptoms, 60 were diagnosed as having hypertensive cardiovascular disease, 27 mitral valve prolapse syndrome, and 28 chronic fatigue syndrome. These symptoms are common with diastolic dysfunction, and diastolic function is energy dependent. All patients had blood pressure, clinical status, coenzyme Q10 (CoQ10) blood levels and echocardiographic measurement of diastolic function, systolic function, and myocardial thickness recorded before and after CoQ10 replacement.

At control, 63 patients were functional class III and 54 class II; all showed diastolic dysfunction; the mean CoQ10 blood level was 0.855 micrograms/ml; 65%, 15%, and 7% showed significant myocardial hypertrophy, and 87%, 30%, and 11% had elevated blood pressure readings in hypertensive disease, mitral valve prolapse and chronic fatigue syndrome respectively. Except for higher blood pressure levels and more myocardial thickening in the hypertensive patients, there was little difference between the three groups.

CoQ10 administration resulted in improvement in all; reduction in high blood pressure in 80%, and improvement in diastolic function in all patients with follow-up echocardiograms to date; a reduction in myocardial thickness in 53% of hypertensives and 36% of the combined prolapse and fatigue syndrome groups; and a reduced fractional shortening in those high at control and an increase in those initially low.(ABSTRACT TRUNCATED AT 250 WORDS)

 

Source: Langsjoen PH, Langsjoen PH, Folkers K. Isolated diastolic dysfunction of the myocardium and its response to CoQ10 treatment. Clin Investig. 1993;71(8 Suppl):S140-4. http://www.ncbi.nlm.nih.gov/pubmed/8241699

 

A case of chronic fatigue syndrome who showed a beneficial effect by intravenous administration of magnesium sulphate

Abstract:

We have treated a case of chronic fatigue syndrome with atopic diathesis was had suffered general malaise, low grade fever, swelling of the lymph nodes, myalgias and arthralgias for a long time.

A 29-year-old female, who had been treated for atopic dermatitis for 5 years, complained of general malaise in May 1990. She was admitted to the nearest hospital in December 1990 because of low grade fever, swelling of the lymph nodes and an elevation of antinuclear antibody (2520x). She was transferred to our hospital in May 1991.

A diagnosis of collagen disease was not compatible with her condition. In addition to general malaise, fever and lymph node swelling, headache, myalgias, muscle weakness, arthralgias and insomnia were observed, and a diagnosis of chronic fatigue syndrome was made based on the working case definition proposed by Holmes et al.

Although eosinophilia, a high serum level of IgE, and elevation of RAST scores, low NK and ADCC activity, and a reduced level of NK cells in the peripheral blood were detected, serum antibodies to a number of viruses were in the normal range.

Treatments with non-steroid anti-inflammatory drugs, minor tranquilizers and antidepressant drugs were not effective at all. An administration of magnesium sulphate was intravenously performed once a week in order to improve her condition, especially severe general malaise. After about 6-week’s administration of magnesium sulphate, she noticed reduced easy fatigability and an improvement in her impaired daily activities. Finally she was able to leave the hospital in January 1992.(ABSTRACT TRUNCATED AT 250 WORDS)

 

Source: Takahashi H, Imai K, Katanuma A, Sugaya T, Hisano K, Motoya S, Aoki S, Sugiyama T, Yachi. A case of chronic fatigue syndrome who showed a beneficial effect by intravenous administration of magnesium sulphate. Arerugi. 1992 Nov;41(11):1605-10. [Article in Japanese] http://www.ncbi.nlm.nih.gov/pubmed/1492795

 

Bupropion treatment of fluoxetine-resistant chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) includes many symptoms of major depression. For this reason, many antidepressants have been used to treat the symptoms of this disorder. Among the more recently released antidepressants are fluoxetine and bupropion.

In this open study, nine CFS patients who either could not tolerate or did not respond to fluoxetine showed significant response when administered 300 mg/day of bupropion for an 8-week period in both rating of HDRS (t = 4.80, p < 0.01) and BDI (t = 2.48, p < 0.05). Furthermore, bupropion improvement in Hamilton Depression Rating Scale correlated significantly with change in plasma homovanillic acid (HVA) (r = 0.96, p < 0.01).

Plasma total methylhydroxyphenolglycol (MHPG) also increased significantly during bupropion treatment (t = 2.37, p = 0.05). Measures of T1 microsomal antibodies also decreased over treatment time; increases in natural killer cell numbers correlated inversely with change in plasma levels of free MHPG (r = -0.88, p < 0.05). Bupropion responders were more likely to have trough blood levels above 30 ng/ml (chi 2 = 3.6, p = 0.05).

 

Source: Goodnick PJ, Sandoval R, Brickman A, Klimas NG. Bupropion treatment of fluoxetine-resistant chronic fatigue syndrome. Biol Psychiatry. 1992 Nov 1;32(9):834-8. http://www.ncbi.nlm.nih.gov/pubmed/1450297

 

Chronic fatigue syndrome, a case of high anti-HHV-6 antibody titer and one associated with primary hyperaldosteronism

Abstract:

Two cases of chronic fatigue syndrome (CFS) were reported which were suggestive for the study of the etiology and a cure for CFS.

Case 1: A 31-year-old woman was admitted for chronic fatigue syndrome. Examination revealed a high titer of anti HHV-6 antigen of x2560 and an increased percentage of suppressor T lymphocytes in the peripheral blood. HHV-6 was speculated to be reactivated and stimulating the immune system in CFS.

Case 2: A 46-year-old woman suffering from CFS had been in remission for 6 years. She was admitted for hypertension associated with right adrenal adenoma and hyperaldosteronism. After right adrenalectomy, there was a recurrence of high fever and other CFS symptoms. It was suggested that CFS symptoms may be ameliorated by aldosterone.

 

Source: Kato Y, Kamijima S, Kashiwagi A, Oguri T. Chronic fatigue syndrome, a case of high anti-HHV-6 antibody titer and one associated with primary hyperaldosteronism. Nihon Rinsho. 1992 Nov;50(11):2673-8. [Article in Japanese] http://www.ncbi.nlm.nih.gov/pubmed/1337563