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

 

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

 

Neuro-psychiatric aspects of chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is easily differentiated from various neurological organic disorders by conventional clinical examinations. The most important disease for distinguishment from CFS is fibromyalgia syndrome, in which the prominent and cardinal feature is a deprivation of stage 4 slow wave sleep.

Experimentally, the sleep disturbance in controls can induce general myalgia, muscle tender points, severe fatigue and stiffness on awakening. The EEG abnormality is slow alpha wave contaminants on slow wave background, which is identical to EEG of CFS. The results clearly imply that CFS is not a hysterical or psychogenic disease, and that fibromyalgia may be a central fundamental of CFS.

Fibromyalgia, however, has distinct features such as no antecedent inflammatory process and no endemics. Therefore, the syndrome has features distinct from, in addition to common features to CFS. It is also very difficult to distinguish CFS from depression. The above-mentioned features can be observed in depression. Now, study of brain blood flow or metabolism by PET or SPECT can be a possible tool for establishment of the CFS identity.

 

Source: Shimizu T. Neuro-psychiatric aspects of chronic fatigue syndrome. Nihon Rinsho. 1992 Nov;50(11):2630-4. [Article in Japanese] http://www.ncbi.nlm.nih.gov/pubmed/1287239

 

Fluctuations in perceived energy and mood among patients with chronic fatigue syndrome

Comment on: Fluctuations in perceived energy and mood among patients with chronic fatigue syndrome. [J R Soc Med. 1992]

 

As one who has long had a high regard for Dr Shepherd’s reasoned arguments in. the area of chronic fatigue syndrome (CFS) (September. 1992 JRSM, p 588), I am sorry to have to point out a logical inconsistency in his assessment of our work. Postinfectious patients do indeed form a sub-group of those with chronic fatigue syndrome. However, according to the ‘Oxford criteria’, in defining other groups of chronically fatigued patients, a diagnosis of previous infection is not necessary. Thus precipitating infection is not necessary for defining the syndrome itself, as we said in our paper.

Secondly, he might do well to note the way in which our results show energy and mood levels among CFS patients to be at their highest in the midmorning. This does not appear to be the pattern typically found among individuals with a primary diagnosis of depression, as we also point out. We regard this distinction as being potentially important and would hope.that the ME Association might wish to consider its implications. Unfortunately, this point was also missed in a recently unsolicited ‘abstraction’ of our work kindly prepared for us by the International Federation of ME Associations to be published in their Medical Update.

You can read the rest of this letter here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1293708/pdf/jrsocmed00106-0076.pdf

 

Source: Wood C. Fluctuations in perceived energy and mood among patients with chronic fatigue syndrome. J R Soc Med. 1992 Oct;85(10):650. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1293708/

 

Immunological and psychological dysfunction in patients receiving immunotherapy for chronic fatigue syndrome

Abstract:

Associations between immunological and psychological dysfunction in 33 patients with Chronic Fatigue Syndrome (CFS) were examined before and in response to treatment in a double blind, placebo-controlled trial of high dose intravenous immunoglobulin. Only those patients who received active immunotherapy demonstrated a consistent pattern of correlations between improvement in depressive symptoms and markers of cell-mediated immunity (CMI).

This finding lends some support to the hypothesis that depressive symptoms in patients with CFS occur secondary to, or share a common pathophysiology with, immunological dysfunction. This pattern and the lack of strong associations between depression and immunological disturbance prior to treatment are less supportive of the view that CFS is primarily a form of depressive disorder or that immunological dysfunction in patients with CFS is secondary to concurrent depression.

 

Source: Hickie I, Lloyd A, Wakefield D. Immunological and psychological dysfunction in patients receiving immunotherapy for chronic fatigue syndrome. Aust N Z J Psychiatry. 1992 Jun;26(2):249-56. http://www.ncbi.nlm.nih.gov/pubmed/1642616

 

Fluctuations in perceived energy and mood among patients with chronic fatigue syndrome

Comment in: Fluctuations in perceived energy and mood among patients with chronic fatigue syndrome. [J R Soc Med. 1992]

Comment on: Fluctuations in perceived energy and mood among patients with chronic fatigue syndrome. [J R Soc Med. 1992]

 

I find it surprising that Wood et al. (April 992 JRSM, p 195) no longer appear to consider,that the presence of a precipitating infection should be necessary for the selection of patients involved in the study of chronic fatigue syndromes. The reference they quote, which refers to guidelines laid down at Oxford in 1990, states very clearly that post-infectious patients with chronic fatigue do indeed form a distinct subgroup, and that to fulfil research criteria there, must be,’definite evidence of infection at onset or presentation’.

Having failed to make such a distinction it is not, altogether surprising that they go on to conclude that the higher levels of depression found in their study …. serve to reinforce the now widely–current, notion that such patients may be suffering from a depressive illness, of which physical fatigue is a somatic manifestation’.

You may read the rest of this comment as well as the author’s response here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1293670/pdf/jrsocmed00107-0092b.pdf

 

Source: Shepherd C. Fluctuations in perceived energy and mood among patients with chronic fatigue syndrome. J R Soc Med. 1992 Sep;85(9):588. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1293670/

 

Monospot and VP1 tests in chronic fatigue syndrome and major depression

Abstract:

Thirty-four patients with chronic fatigue syndrome (CFS) were compared with controls with DSM-III-R major depression on the Monospot and VP1 antigen tests.

There was no significant difference in the numbers initially VP1 positive in the groups (11/34 and 7/34 positive in the chronic fatigue and major depression group respectively). Four CFS but no depressed patients were Monospot positive initially. No patient was both Monospot and VP1 positive. Patients positive on the tests were offered a repeat 6 months later. Eight of the 11 VP1 positive patients in the CFS group were retested and four remained positive, but none of the four depressed patients retested remained positive. No patient retested remained Monospot positive.

The Monospot and VP1 tests appear to have little discriminating ability between these groups as screening tests and their predictive validity is unclear.

 

Source: Lynch SP, Seth RV, Main J. Monospot and VP1 tests in chronic fatigue syndrome and major depression. J R Soc Med. 1992 Sep;85(9):537-40. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1293640/ (Full article)

 

Chronic fatigue syndrome criteria. A critique of the requirement for multiple physical complaints

Abstract:

OBJECTIVE: The purpose of this study was to test the hypothesis that the patients with chronic fatigue who have the highest number of medically unexplained physical symptoms over their lifetime would also have the highest prevalence of current and lifetime affective and anxiety disorders, lifetime affective symptoms, and the most functional disability. A further goal was to use this information to modify the current case definition to better identify a subgroup of patients with chronic fatigue syndrome who are less likely to have psychiatric illness.

DESIGN: Two hundred eighty-five consecutive patients with chronic fatigue were interviewed with the National Institute of Mental Health Diagnostic Interview Schedule and completed four self-rating questionnaires measuring psychologic distress, functional disability, and the tendency to amplify symptoms. Based on previously published data, patients were divided into four groups with a progressively higher number of lifetime medically unexplained physical symptoms. The prevalence of current and lifetime psychiatric disorders, lifetime psychologic symptoms, and extent of functional impairment was then compared in these four groups of patients.

MAIN RESULTS: The prevalence of current and lifetime psychiatric diagnosis and lifetime depressive symptoms increased linearly with the number of lifetime physical symptoms that the patient experienced. The extent of impairment in activities of daily living and the tendency to amplify symptoms also increased linearly with the number of medically unexplained physical symptoms.

CONCLUSION: The patients with the highest numbers of medically unexplained physical symptoms had extraordinarily high rates of current and lifetime psychiatric disorders. These data suggest that the current case definition for chronic fatigue syndrome inadvertently selects for patients with the highest prevalence of lifetime psychiatric diagnoses. A recommendation based on these results is to modify the case criteria for chronic fatigue syndrome to include patients with fatigue and few physical symptoms and to identify and consider excluding patients with high numbers of physical complaints.

Comment in: Defining the chronic fatigue syndrome. [Arch Intern Med. 1992]

 

Source: Katon W, Russo J. Chronic fatigue syndrome criteria. A critique of the requirement for multiple physical complaints. Arch Intern Med. 1992 Aug;152(8):1604-9. http://www.ncbi.nlm.nih.gov/pubmed/1497394

 

Postviral fatigue syndrome

Comment on: Possible upregulation of hypothalamic 5-hydroxytryptamine receptors in patients with postviral fatigue syndrome. [BMJ. 1992]

 

EDITOR, -A M 0 Bakheit and colleagues recently reported’ a possible upregulation of hypothalamic 5-hydroxytryptamine receptors in patients with the postviral fatigue syndrome, giving some evidence for hypothalamic functional abnormalities in these patients, which are different from others with depression. There is a growing body of evidence which claims that this clinical condition is organic and cannot be simply perceived as a somatisation disorder in patients with predisposition to psychiatric disease.”

We reviewed and quantitatively analysed with Ceretec and single photon emission tomography the brain perfusion of 14 patients fulfilling the Oxford criteria for diagnosis of myalgic encephalomyelitis. They had all had disease for more than six months (more than half the time) manifested with generalised malaise and myalgia, as well as significant physical and intellectual disability. None had any medical condition known to produce fatigue or had recently or in the past had psychiatric disease. When compared with a group of 24 nondepressed age and sex matched controls (normal volunteers) there was significant reduction of the perfusion to several areas of the brain cortex but particularly the brain stem (table).

You can read the rest of this comment here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1882397/pdf/bmj00077-0053b.pdf

 

Source: Costa DC, Brostoff J, Douli V, Ell PJ. Postviral fatigue syndrome. BMJ. 1992 Jun 13;304(6841):1567. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1882397/