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

 

Central basis of muscle fatigue in chronic fatigue syndrome

Abstract:

We studied whether muscle fatigue, metabolism, or activation are abnormal in the chronic fatigue syndrome (CFS). Subjects performed both an intermittent submaximal and a sustained maximal voluntary isometric exercise protocol of the tibialis anterior muscle.

The extent of fatigue, metabolic response, and changes in both M-wave amplitude and twitch tension during exercise were similar in patients and controls. The response to systemic exercise was also normal in the patients. However, voluntary activation of the tibialis was significantly lower in the patients during maximal sustained exercise.

The results indicate that patients with CFS have (1) normal fatigability and metabolism at both the intracellular and systemic levels, (2) normal muscle membrane function and excitation-contraction coupling, and (3) an inability to fully activate skeletal muscle during intense, sustained exercise. This failure of activation was well in excess of that found in controls, suggesting an important central component of muscle fatigue in CFS.

Comment in: Chronic fatigue syndrome. [Neurology. 1993]

 

Source: Kent-Braun JA, Sharma KR, Weiner MW, Massie B, Miller RG. Central basis of muscle fatigue in chronic fatigue syndrome. Neurology. 1993 Jan;43(1):125-31. http://www.ncbi.nlm.nih.gov/pubmed/8423875

 

Persistence of enterovirus RNA in muscle biopsy samples suggests that some cases of chronic fatigue syndrome result from a previous, inflammatory viral myopathy

Abstract:

Molecular hybridization using an enterovirus group specific probe detected virus RNA in muscle biopsy samples from 25 of 96 cases of inflammatory muscle disease and similarly from 41 of 158 cases of postviral fatigue syndrome (PFS).

Enterovirus RNA was detected in only two of 152 samples of control muscle. The inflammatory myopathy group comprised patients with polymyositis (PM), juvenile dermatomyositis (JDM) or adult dermatomyositis (DM), and all showed the presence of an inflammatory infiltrate and fiber necrosis on histological examination of a muscle biopsy sample.

In contrast, muscle samples from the PFS group were histologically normal except for non-specific changes such as occasional single fiber atrophy. By analogy with enteroviral myocarditis, which can progress to a post-inflammatory disease with persistence of virus in myocardium and disposes to the rapid development of dilated cardiomyopathy, we propose that PFS syndrome may be a sequela of a previous inflammatory viral myopathy.

 

Source: Bowles NE, Bayston TA, Zhang HY, Doyle D, Lane RJ, Cunningham L, Archard LC. Persistence of enterovirus RNA in muscle biopsy samples suggests that some cases of chronic fatigue syndrome result from a previous, inflammatory viral myopathy. J Med. 1993;24(2-3):145-60. http://www.ncbi.nlm.nih.gov/pubmed/8409778

 

Epidemiology of chronic fatigue syndrome: the Centers for Disease Control Study

Abstract:

The US Centers for Disease Control initiated physician-based chronic fatigue syndrome (CFS) surveillance systems in four cities in September 1989 to determine the prevalence, incidence, course and impact of the illness. The participating physicians have referred to our surveillance system 590 patients who were ill during the first two years of surveillance with severe, debilitating, unexplained fatigue for at least the preceding six months.

Referred patients were screened for psychiatric disorders preceding, concurrent with, and subsequent to the onset of their fatigue by specially trained nurses using a modified Diagnostic Interview Schedule. Complete health histories were obtained by interview and review of medical records and a basic panel of standard laboratory diagnostic tests were conducted. Four physicians have independently reviewed the health information of 337 of the patients for classification.

Approximately 26% of patients referred to the surveillance system met the CFS case definition in all regards, 14% lacked one or more of the required eight symptom criteria, 15% were judged to have another possible or known medical illness which could account for the severe fatigue, and the remaining 45% did not meet the case definition because of histories of psychiatric disorders preceding the onset of fatigue.

Minimum prevalence rates for the period 1 September 1989 to 1 September 1991 ranged from 2.0 to 7.3 per 100,000 of the general population across the four study sites and rates based on prorated data ranged from 4.6 to 11.3 per 100,000. More than 80% of the CFS cases were female, most were white, and their average age at onset was approximately 30 years.

 

Source: Gunn WJ, Connell DB, Randall B. Epidemiology of chronic fatigue syndrome: the Centers for Disease Control Study. Ciba Found Symp. 1993;173:83-93; discussion 93-101. http://www.ncbi.nlm.nih.gov/pubmed/8387910

 

Investigation of retroviral involvement in chronic fatigue syndrome

Abstract:

Within the last few years significant efforts have been made to identify objective reliable diagnostic markers from individuals with chronic fatigue syndrome (CFS).

We report the absence of a previously described retroviral marker (HTLV-II gag) in a blinded study of CFS cases. Even with excellent reproducible sensitivities, this marker failed in repeated attempts to distinguish cases from controls. In addition, four other retroviruses (simian T cell leukaemia virus, human spumavirus, bovine leukaemia virus and simian retrovirus) were examined for their presence in these CFS cases and found to be absent.

Our findings suggest that these agents, at least as markers, are non-distinguishing for CFS and that other factors may be confounding the resolution of an aetiology to this syndrome.

 

Source: Folks TM, Heneine W, Khan A, Woods T, Chapman L, Schonberger L. Investigation of retroviral involvement in chronic fatigue syndrome. Ciba Found Symp. 1993;173:160-6; discussion 166-75. http://www.ncbi.nlm.nih.gov/pubmed/8387909

 

Enteroviruses and postviral fatigue syndrome

Abstract:

Postviral fatigue syndrome (PFS) occurs both in epidemics and sporadically. Many of the original epidemics were related to poliomyelitis outbreaks which either preceded or followed them.

The core clinical symptoms are always the same: severe fatigue made worse by exercise, myalgia, night sweats, atypical depression and excessive sleep. The other common symptoms include dysequilibrium disorders and irritable bowel syndrome.

We have detected enteroviral genome sequences in muscle biopsies from cases of PFS, using specific enteroviral oligonucleotide primers in the polymerase chain reaction (PCR). In addition, whole virus particles can be demonstrated in PCR-positive muscle, using solid-phase immuno-electron microscopy.

An increase in the number and size of muscle mitochondria was found in 70% of PFS cases, suggesting an abnormality in metabolic function. Evidence of hypothalamic dysfunction was present, particularly involving 5-hydroxytryptamine metabolism.

A putative model of PFS, based on persistent enteroviral infection in laboratory mice, revealed resolving inflammatory lesions in muscle with, however, a marked increase in the production of certain cytokines in the brain. This model may help to explain the pathogenesis of PFS.

 

Source: Behan PO, Behan WM, Gow JW, Cavanagh H, Gillespie S. Ciba Found Symp. 1993;173:146-54; discussion 154-9. http://www.ncbi.nlm.nih.gov/pubmed/8387908

 

Studies of herpesvirus infection in chronic fatigue syndrome

Abstract:

The relationship of herpesviruses to chronic fatigue syndrome has received considerable attention over the past decade. Data suggesting an association fall into three major categories.

First, among acute precipitants of the syndrome are primary infections with some herpesviruses, most notably Epstein-Barr virus and cytomegalovirus.

Second, a series of studies have detailed elevations of antibodies to most herpesviruses in selected chronic fatigue syndrome populations, with Epstein-Barr virus and human herpes type 6 being the objects of most scrutiny.

Third, one recent study reported a greater ease of recovery of human herpes virus type 6 from chronic fatigue syndrome patients. This review article critically examines the cumulative data regarding an association between one or more herpesviruses and the chronic fatigue syndrome in the context of the known biology and epidemiology of these agents.

In view of these, and additional considerations regarding study methodologies, the conclusion is drawn that herpesviruses are not dominant causes of the chronic fatigue syndrome and may not even be necessary to the perpetuation of the illness, but it is premature to dismiss entirely this latter possibility.

 

Source: Straus SE. Studies of herpesvirus infection in chronic fatigue syndrome. Ciba Found Symp. 1993;173:132-9; discussion 139-45. http://www.ncbi.nlm.nih.gov/pubmed/8387907

 

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

 

Lymphocyte phenotype and function in the chronic fatigue syndrome

Abstract:

Lymphocytes of 18 patients meeting the Centers for Disease Control (CDC) case definition for the chronic fatigue syndrome (CFS), 10 similar, chronically fatigued patients not fully conforming to the CDC case definition, and 17 matched, healthy individuals were studied to determine the presence of abnormalities of peripheral cell phenotype and function.

Extensive phenotypic analyses of B- and T-cell subsets, natural killer (NK) cells, and macrophages were performed using single-, dual-, and three-color flow cytometry. Compared to controls, in CFS patients the percentage of CD4 T cells and CD4,CD45RA, or naive T cells, was reduced. The CD4,CD45RO, or memory T-cell, subset was numerically normal but expressed increased levels of adhesion markers (CD29, CD54, and CD58). CFS patient lymphocytes showed reduced proliferative responses to phytohemagglutinin, concanavalin A, and staphylococcal enterotoxin B. Lymphocytes from fatigue patients not meeting the CDC definition showed similar abnormalities.

These data indicate that peripheral T cells manifest an increased state of differentiation in CFS and related conditions. This may arise as a consequence of an underlying neuropsychiatric and/or neuroendocrine disorder or because of exposure to antigens or superantigens of an infectious agent.

 

Source: Straus SE, Fritz S, Dale JK, Gould B, Strober W. Lymphocyte phenotype and function in the chronic fatigue syndrome. J Clin Immunol. 1993 Jan;13(1):30-40. http://www.ncbi.nlm.nih.gov/pubmed/8095270

 

Japanese patients with chronic fatigue syndrome are negative for known retrovirus infections

Abstract:

Although chronic fatigue syndrome (CFS) is known to be the syndrome that begins with an acute flu-like illness that may be due to the exposure to an infectious agent, there has been no convincing evidence on the causative agents.

Recently, human T-lymphotropic virus type II (HTLV-II)-like virus has been reported to be associated with the CFS by using HTLV Western blot analysis and polymerase chain reaction. However, some investigators could not detect HTLV-II by indirect immunofluorescence analysis.

Lately, CFS patients have been reported in Japan. We detected all 30 tested patients with CFS were seronegative for HTLV-II, HTLV-I and HIV by specific peptide ELISA and Western blot. Further, PCR analysis was negative for HTLV-II and retrovirus was not detected by coculture method with patients’ PBMC. Thus, known human retrovirus infections do not cause a CFS in Japan.

 

Source: Honda M, Kitamura K, Nakasone T, Fukushima Y, Matsuda S, Nishioka K, Matsuda J, Hashimoto N, Yamazaki S. Japanese patients with chronic fatigue syndrome are negative for known retrovirus infections. Microbiol Immunol. 1993;37(10):779-84. http://www.ncbi.nlm.nih.gov/pubmed/7507200