Treatment of chronic fatigue syndrome with 5-HT3 receptor antagonists–preliminary results

Abstract:

OBJECTIVE: The serotonin system presumably is involved in the pathogenesis of chronic fatigue syndrome (CFS). Results from a few studies led to the hypothesis of a “postsynaptic hyperresponsiveness” in CFS. Therefore we intended to evaluate the efficacy of 5-HT3 receptor antagonists in the treatment of CFS.

PATIENTS AND METHODS: 2 patient groups (10 patients each; CFS according to the CDC classification criteria) received either oral tropisetron (5 mg once daily) or oral ondansetron (2 x 8 mg daily), open-labelled. Treatment duration was 15 days. Treatment response was evaluated by visual analog scales (VAS) for fatigue and capability.

RESULTS: 19 patients finished their respective study. In the tropisetron group 6/9 (VAS fatigue) and 7/9 (VAS capability) patients documented benefit, 8/10 rsp. 8/10 patients in the ondansetron group. The score changes (VAS before and after treatment) in case of response were more pronounced in the tropisetron group. The frequency of concomitant symptoms did not differ significantly in the treatment groups. The overall analysis of both studies showed a remarkable improvement (> or = 35%) of approximately one third of the patients in both VAS. Treatment was well tolerated.

CONCLUSION: Our preliminary results encourage to perform placebo-controlled, double-blind studies to further evaluate the efficacy of 5-HT3 receptor antagonists in the treatment of CFS.

Source: Späth M, Welzel D, Färber L. Treatment of chronic fatigue syndrome with 5-HT3 receptor antagonists–preliminary results. Scand J Rheumatol Suppl. 2000;113:72-7. http://www.ncbi.nlm.nih.gov/pubmed/11028837

Chronic fatigue syndrome, fibromyalgia, and multiple chemical sensitivities in a community-based sample of persons with chronic fatigue syndrome-like symptoms

Abstract:

OBJECTIVE: The aim of this study was to determine illness comorbidity rates for individuals with chronic fatigue syndrome (CFS), fibromyalgia (FM), and multiple chemical sensitivities (MCS). An additional objective was to identify characteristics related to the severity of fatigue, disability, and psychiatric comorbidity in each of these illness groups.

METHODS: A random sample of 18,675 residents in Chicago, Illinois, was first interviewed by telephone. A control group and a group of individuals with chronic fatigue accompanied by at least four minor symptoms associated with CFS received medical and psychiatric examinations.

RESULTS: Of the 32 individuals with CFS, 40.6% met criteria for MCS and 15.6% met criteria for FM. Individuals with MCS or more than one diagnosis reported more physical fatigue than those with no diagnosis. Individuals with more than one diagnosis also reported greater mental fatigue and were less likely to be working than those with no diagnosis. Individuals with CFS, MCS, FM, or more than one diagnosis reported greater disability than those with no diagnosis.

CONCLUSIONS: Rates of coexisting disorders were lower than those reported in prior studies. Discrepancies may be in part attributable to differences in sampling procedures. People with CFS, MCS, or FM endure significant disability in terms of physical, occupational, and social functioning, and those with more than one of these diagnoses also report greater severity of physical and mental fatigue. The findings illustrate differences among the illness groups in the range of functional impairment experienced.

 

Source: Jason LA, Taylor RR, Kennedy CL. Chronic fatigue syndrome, fibromyalgia, and multiple chemical sensitivities in a community-based sample of persons with chronic fatigue syndrome-like symptoms. Psychosom Med. 2000 Sep-Oct;62(5):655-63. http://www.ncbi.nlm.nih.gov/pubmed/11020095

 

Longitudinal analysis of symptoms reported by patients with chronic fatigue syndrome

Abstract:

PURPOSE: To determine the effect of chronic fatigue syndrome (CFS) illness duration and onset type on the likelihood of reporting a symptom during successive follow-up periods.

METHODS: In 1997, a two-phase RDD survey in Wichita, Kansas, was conducted to estimate the prevalence of CFS. Phase I identified 56,154 respondents 18-69 years of age and screened for severe fatigue, extreme tiredness or exhaustion lasting for 1 month or longer. In phase II an equal number of fatigued (n = 7,176) and randomly selected non-fatigued subjects were asked about 8 CFS and 13 non-CFS symptoms, as well as the presence of specific medical and psychiatric conditions. Eligible respondents were clinically evaluated to establish CFS diagnosis. Phase II respondents were re-contacted at 12- (n = 4,331) and 24-months (n = 4,266) for additional follow-up and diagnosis. In this study we considered symptoms reported as being present most of the time during each successive observation period. Generalized estimating equations were used to model symptoms over time and to address study questions. Such a model accounts for correlations among repeated symptoms for each subject. We used an auto-regressive structure for the correlation matrix, assuming the correlations between each pair of repeated symptoms should decrease as the time between symptoms increased.

RESULTS: There were 74 CFS patients who had been ill for 1 to 20 years (median = 6.3 years). Among these, 46 reported gradual and 28 reported sudden onset. Symptoms fluctuated over the course of illness. However, only stomach pain (non-CFS symptom) was more likely to be reported as duration of illness increased (p < 0.05). There was no association between onset type and the likelihood of reporting a symptom during an interview, except that chills and severe headaches were more likely to be reported by sudden cases.

CONCLUSIONS: The likelihood of expressing CFS and non-CFS symptom “most of the time” is the same across years of illness. More analyses are warranted to consider expression of symptoms for >/=6 months and severe symptoms.

 

Source: Nisenbaum R, Jones A, Jones J, Reeves W. Longitudinal analysis of symptoms reported by patients with chronic fatigue syndrome. Ann Epidemiol. 2000 Oct 1;10(7):458. http://www.ncbi.nlm.nih.gov/pubmed/11018368

 

Psychiatric correlates in chronic fatigue syndrome

Abstract:

PURPOSE: This study presents psychiatric correlates in Chronic Fatigue Syndrome (CFS) that emerged from the CDC’s Surveillance Study. It seeks to determine the time of onset and rates of syndromal psychiatric disorders and identify the predominant disorder. Other goals are to ascertain whether depression is associated with CFS symptomatology, compare syndromal to self- reported depression, and test for the specificity of the 1988 CDC case definition for CFS.

METHODS: All 565 enrolled subjects had fatiguing illnesses and were evaluated for CFS. They completed the Diagnostic Interview Schedule for the DSM-III-R and the Beck Depression Inventory. Prevalence estimates for current syndromal psychiatric disorders were calculated. CFS symptoms were compared by depression status. Syndromal and self-reported depression were contrasted. Groups that did and did not meet the case definition were compared by three outcome variables.

RESULTS: Rates of current psychiatric disorders were high in CDC subjects compared to the community. The predominant disorder was depression. Although prior disorders tended to persist (75%), many disorders were incident to the fatiguing illness (57%). Depression was not associated with increased CFS symptomatology. There was only weak agreement between measures of syndromal and self-reported depression (kappa = 0.3219). Subjects designated as CFS had similar rates of syndromal psychiatric disorders, syndromal depression, and self-reported depression as did non-CFS subjects.

CONCLUSIONS: Current syndrome; psychiatric disorders appear associated with fatiguing illnesses. While prior psychiatric disorders are risk factors for current, the onset was largely concurrent with the fatiguing illnesses. The BDI should probably not be used as a measure for psychiatric morbidity in CFS subjects. Regardless of outcome, there was no evidence of specificity of psychiatric features to the CDC case definition.

 

Source: Axe E, Satz P. Psychiatric correlates in chronic fatigue syndrome. Ann Epidemiol. 2000 Oct 1;10(7):458. http://www.ncbi.nlm.nih.gov/pubmed/11018367

 

Chronic fatigue syndrome: occupation, medical utilization, and subtypes in a community-based sample

Abstract:

Most studies of chronic fatigue syndrome (CFS) have been based on patients recruited from primary or tertiary care settings. Patients from such settings might not be typical of patients in the general population. The present investigation involved examining individuals with CFS from a community-based study. A random sample of 18,675 respondents in Chicago was first interviewed by telephone. A group of individuals with chronic fatigue accompanied by at least four minor symptoms associated with CFS were given medical and psychiatric examinations. From this sample, a physician review group diagnosed individuals with CFS.

Those diagnosed with CFS were subclassified based on a variety of categories, including duration of illness, mode of illness onset, and presence or absence of a stressful life event directly preceding onset. In addition, we examined medical utilization among those diagnosed with CFS, as well as whether individuals with CFS were disproportionately represented in health care professions. Important differences emerged on measures of sociodemographics, symptoms, and functional disability. The implications of these findings and others are discussed.

 

Source: Jason LA, Taylor RR, Kennedy CL, Song S, Johnson D, Torres S. Chronic fatigue syndrome: occupation, medical utilization, and subtypes in a community-based sample. J Nerv Ment Dis. 2000 Sep;188(9):568-76. http://www.ncbi.nlm.nih.gov/pubmed/11009329

 

Pain complaints in patients with fibromyalgia versus chronic fatigue syndrome

Abstract:

Individuals with fibromyalgia (FM) and/or chronic fatigue syndrome (CFS) report arthralgias and myalgias. However, only persons with FM alone exhibit abnormal pain responses to mild levels of stimulation, or allodynia. We identify the abnormalities in the neuroendocrine axes that are common to FM and CFS as well as the abnormalities in central neuropeptide levels and functional brain activity that differentiate these disorders. These two sets of factors, respectively, may account for the similarities and differences in the pain experiences of persons with FM and CFS.

 

Source: Bradley LA, McKendree-Smith NL, Alarcón GS. Pain complaints in patients with fibromyalgia versus chronic fatigue syndrome. Curr Rev Pain. 2000;4(2):148-57. http://www.ncbi.nlm.nih.gov/pubmed/10998728

 

Decreased bone mineral density during low dose glucocorticoid administration in a randomized, placebo controlled trial

Abstract:

OBJECTIVE: While osteoporosis and bone fractures are clearly recognized side effects of high dose glucocorticoids, the effect of low dose glucocorticoids remains controversial. We investigated the effect of 3 months of low dose hydrocortisone on bone mineral density (BMD).

METHODS: Subjects, 18 to 55 years old with chronic fatigue syndrome and no medical or psychiatric illness requiring medication, were randomized in a double blind, placebo controlled trial to receive oral hydrocortisone, 13 mg/m2 body surface area every morning and 3 mg/m2 every afternoon (25 to 35 mg/day, equivalent to about 7.5 mg prednisone/day) or placebo for 12 weeks. Before and after treatment BMD of the lumbar spine was measured by dual energy x-ray absorptiometry.

RESULTS: We studied 23 subjects (19 women, 4 men). For the 11 hydrocortisone recipients there was a mean decrease in BMD: mean change from baseline of the lateral spine was -2.0% (95% CI -3.5 to -0.6. p = 0.03) and mean change of the anteroposterior spine was -0.8% (95% CI -1.5 to -0.1, p = 0.06). Corresponding changes for the 12 placebo recipients were +1.0% (95% CI -1.0 to 3.0, p = 0.34) and +0.2% (95% CI -1.4 to 1.5, p = 0.76).

CONCLUSION: A 12 week course of low dose glucocorticoids given to ambulatory subjects with chronic fatigue syndrome was associated with a decrease in BMD of the lumbar spine. This decrease was statistically significant in lateral spine measurements and nearly so in anteroposterior spine measurements.

 

Source: McKenzie R, Reynolds JC, O’Fallon A, Dale J, Deloria M, Blackwelder W, Straus SE. Decreased bone mineral density during low dose glucocorticoid administration in a randomized, placebo controlled trial. J Rheumatol. 2000 Sep;27(9):2222-6. http://www.ncbi.nlm.nih.gov/pubmed/10990237

 

Effect of growth hormone treatment in patients with chronic fatigue syndrome: a preliminary study

Abstract:

The efficacy of growth hormone (GH) therapy was evaluated in patients with chronic fatigue syndrome (CFS) who had peak serum GH levels below 10 microg/l during stage-controlled sleep. Twenty patients (7 men, 13 women; age range, 30-60 years) with CFS were randomized to receive placebo or GH therapy, 6.7 microg/kg/day (0.02 IU/kg/day), for 12 weeks.

Following this double-blind treatment period, the 17 patients remaining in the study were given GH therapy at the above dose for an open period of 9 months. Mean (+/- SD) serum levels of insulin-like growth factor I (IGF-I) increased during GH treatment, from 173 +/- 46 microg/I to 296 +/- 89 microg/l (P < 0.001); IGF-I SDS values increased from -0.45 +/- 1.14 to +1.43 +/- 1.09 (P < 0.001).

Fat-free mass and total body water were significantly increased after 12 months of treatment. Although quality of life, as assessed using two different questionnaires, did not improve significantly during GH treatment, four patients were able to resume work after a long period of sick leave.

 

Source: Moorkens G, Wynants H, Abs R. Effect of growth hormone treatment in patients with chronic fatigue syndrome: a preliminary study. Growth Horm IGF Res. 1998 Apr;8 Suppl B:131-3. http://www.ncbi.nlm.nih.gov/pubmed/10990148

 

Secretion of growth hormone in patients with chronic fatigue syndrome

Abstract:

Decreased serum levels of insulin-like growth factor I (IGF-I) are common in patients with fibromyalgia, which is frequently associated withchronic fatigue syndrome (CFS). Twenty patients with CFS (7 men, 13 women; age range, 30-60 years) and age- and sex-matched controls were tested for peak GH responses to insulin-induced hypoglycaemia and arginine administration. Nocturnal secretion of GH and serum levels of IGF-I were also measured. Serum IGF-I SDS (+/- SD) was significantly lower in patients with CFS than in controls (SDS, -0.39 +/- 1.07 vs 0.33 +/- 0.84; P = 0.02). Patients with CFS also tended to have reduced nocturnal secretion of GH (area under the curve, 32.4 +/- 18.3 vs 62.7 +/- 43.7 microg/l/15 minutes; P= 0.06), but peak GH responses to insulin-induced hypoglycaemia and arginine administration did not differ significantly between the two groups. It is not clear whether the tendency for impaired spontaneous nocturnal GH secretion in patients with CFS is a cause or an effect of the condition.

 

Source: Berwaerts J, Moorkens G, Abs R. Secretion of growth hormone in patients with chronic fatigue syndrome. Growth Horm IGF Res. 1998 Apr;8 Suppl B:127-9. http://www.ncbi.nlm.nih.gov/pubmed/10990147

 

Cerebral perfusion in chronic fatigue syndrome and depression

Abstract:

BACKGROUND: Patients with chronic fatigue syndrome (CFS) and depressive illness share many, but not all, features.

AIMS: To test the hypothesis that patients with CFS have abnormal cerebral perfusion, that differs from that in patients with depressive illness.

METHOD: We recruited 30 patients with CFS who were not depressed, 12 depressed patients and 15 healthy volunteers. Regional cerebral perfusion at rest was assessed using region of interest (ROI) and voxel-based statistical parametric mapping (SPM) techniques.

RESULTS: On SPM analysis there was increased perfusion in the right thalamus, pallidum and putamen in patients with CFS and in those with depressive illness. CFS patients also had increased perfusion in the left thalamus. Depressed patients differed from those with CFS in having relatively less perfusion of the left prefrontal cortex. The results were similar on ROI analysis.

CONCLUSIONS: Abnormal cerebral perfusion patterns in CFS subjects who are not depressed are similar but not identical to those in patients with depressive illness. Thalamic overactivity may be a correlate of increased attention to activity in CFS and depression; reduced prefrontal perfusion in depression may be associated with the greater neuropsychological deficits in that disorder.

Comment in: Chronic fatigue syndrome and depression. [Br J Psychiatry. 2000]

 

Source: MacHale SM, Lawŕie SM, Cavanagh JT, Glabus MF, Murray CL, Goodwin GM, Ebmeier KP. Cerebral perfusion in chronic fatigue syndrome and depression. Br J Psychiatry. 2000 Jun;176:550-6. http://bjp.rcpsych.org/content/176/6/550.long (Full article)