Favourable results of a rehabilitation programme with cognitive behavioural therapy and graded physical activity in patients with the chronic-fatigue syndrome

Abstract:

OBJECTIVE: To determine whether a specific course of interdisciplinary rehabilitation might lead to clinically significant changes in fatigue, experienced disability and physical function in patients with the chronic-fatigue syndrome (CFS).

DESIGN: Prospective and uncontrolled.

METHOD: ‘Het Roessingh’, a rehabilitation centre in Enschede, the Netherlands, has developed an interdisciplinary clinical rehabilitation programme for patients with CFS in cooperation with the ‘Nijmeegs Kenniscentrum Chronische Vermoeidheid’ [Chronic-Fatigue Knowledge Centre] in Nijmegen, the Netherlands. In this programme, physical, mental and social activities are gradually increased on the basis of cognitive behavioural principles and graded activity. Of the 127 successive persons who enrolled for the therapy during the period from August 2000 to December 2004, 99 fulfilled the inclusion criteria; they had a median duration of symptoms of 6 years. The results of treatment were evaluated by a measurement with the ‘Checklist individuele spankracht’ [Checklist individual muscle tone] before and after treatment and the scores on the ‘Patiëntspecifieke beperkingen’ [Patient-specific disability] and the Short form-36. The measured data were complete in 74 patients.

RESULTS: Before rehabilitation, the levels of fatigue, disability and distress were high. After treatment, the studied population showed significant improvement in fatigue, experienced disability and physical function. The magnitude of the improvement was generally ‘average’. At the end of treatment, 70% of the patients were clinically less fatigued, 68% experienced less disability and 55% functioned better physically. In 34% the level of fatigue was normalised after treatment, but 9.5% of the patients was more fatigue.

CONCLUSION: The rehabilitation programme offered for CFS led to significant improvements in function and fatigue.

Comment in: [Treatment of patients with the chronic-fatigue syndrome]. [Ned Tijdschr Geneeskd. 2006]

 

Source: Torenbeek M, Mes CA, van Liere MJ, Schreurs KM, ter Meer R, Kortleven GC, Warmerdam CG. Favourable results of a rehabilitation programme with cognitive behavioural therapy and graded physical activity in patients with the chronic-fatigue syndrome. Ned Tijdschr Geneeskd. 2006 Sep 23;150(38):2088-94. [Article in Dutch] https://www.ncbi.nlm.nih.gov/pubmed/17036861

 

 

Treatment of patients with the chronic-fatigue syndrome

Abstract:

In the last few years, the chronic-fatigue syndrome has been recognised as an important health problem. In a recent report, the Health Council of the Netherlands suggested that the capacity for treatment be increased. Cognitive behavioural therapy and graded exercise training are treatment options of first choice.

A recently published, uncontrolled evaluation of a Dutch clinical rehabilitation programme based partly on these methods proved to be successful. Unfortunately, due to the uncontrolled character of the study, it remains unclear which elements in the treatment were responsible for the success. Which patients should be included in a costly clinical rehabilitation programme also remains unclear. More in general, there is room for empirical studies of treatment allocation, not in the least because of the frequently occurring comorbidity. Good progress has been made in the treatment of the chronic-fatigue syndrome, but we are still far removed from evidence-based, stepped care, treatment programmes.

Comment on: [Favourable results of a rehabilitation programme with cognitive behavioural therapy and graded physical activity in patients with the chronic-fatigue syndrome]. [Ned Tijdschr Geneeskd. 2006]

 

Source: Jonker K, van Hemert AM. Treatment of patients with the chronic-fatigue syndrome. Ned Tijdschr Geneeskd. 2006 Sep 23;150(38):2067-8. [Article in Dutch] https://www.ncbi.nlm.nih.gov/pubmed/17036854

 

An investigation of the long-term benefits of antidepressant medication in the recovery of patients with chronic fatigue syndrome

Abstract:

Two hundred and seventy-five patients fulfilling the Centre for Disease Control (CDC) criteria for Chronic Fatigue Syndrome (CFS) completed measures assessing illness history, global ratings of well being, sleep, activity and psychopathology at baseline, 6 months, 18 months and 3 year follow-up. Forty-nine of these patients had been prescribed antidepressant medication, namely Tricyclic drugs or Selective Serotonin Re-uptake Inhibitors (SSRI).

Data from the current study suggests that patients in the antidepressant medication group recover at a faster rate over time when compared to the untreated patient sample. In addition, the positive effects of antidepressant therapy are maintained at the 3-year follow-up point. It appears from these data that the SSRI in particular are responsible for improvements in the condition. Most importantly, these improvements include a reduction in the levels of fatigue recorded by patients. These findings have not been demonstrated in previous studies of the effect of antidepressant therapy for patients with this illness and this may reflect the short time periods studied in the earlier research.

 

Source: Thomas MA, Smith AP. An investigation of the long-term benefits of antidepressant medication in the recovery of patients with chronic fatigue syndrome. Hum Psychopharmacol. 2006 Dec;21(8):503-9. https://www.ncbi.nlm.nih.gov/pubmed/16981220

 

Azithromycin in chronic fatigue syndrome (CFS), an analysis of clinical data

Abstract:

BACKGROUND: CFS is a clinical state with defined symptoms, but undefined cause. The patients may show a chronic state of immune activation and treatment with an antibiotic in this subgroup has been suggested.

METHODS: In a retrospective study, the response of CFS patients to azithromycin, an antibiotic and immunomodulating drug, has been scored from the patients records and compared with clinical and laboratory data. Azithromycin was not the first choice therapy, but offered when the effect of counseling and L-carnitine was considered insufficient by the patient and the clinician.

RESULTS: Of the 99 patients investigated, 58 reported a decrease in the symptoms by the use of azithromycin. These responding patients had lower levels of plasma acetylcarnitine.

CONCLUSION: The efficacy of azithromycin in the responsive patients could be explained by the modulating effect on a chronic primed state of the immune cells of the brain, or the activated peripheral immune system. Their lower acetylcarnitine levels may reflect a decreased antioxidant defense and/or an increased consumption of acetylcarnitine caused by oxidative stress.

 

Source: Vermeulen RC, Scholte HR. Azithromycin in chronic fatigue syndrome (CFS), an analysis of clinical data. J Transl Med. 2006 Aug 15;4:34. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1562448/ (Full article)

 

Bupropion augmentation in the treatment of chronic fatigue syndrome with coexistent major depression episode

Abstract:

While psychoeducational strategies and general support are always indicated for the treatment of chronic fatigue syndrome (CFS), pharmacological strategies are yet not well established. Antidepressants such as selective serotonin re-uptake inhibitors have been shown to influence positively symptoms and immunological parameters. However, a considerable part of CFS patients do not satisfactorily respond to them. Bupropion, a centrally acting catecholamine-transporter blocker without classic psycho-analeptic properties, shows theoretical potential to improve fatigue symptoms. In the reported case paroxetine was augmented with bupropion at high dosage, a strategy which consecutively led to a rapid relief of CFS-symptoms.

 

Source: Schönfeldt-Lecuona C, Connemann BJ, Wolf RC, Braun M, Freudenmann RW. Bupropion augmentation in the treatment of chronic fatigue syndrome with coexistent major depression episode. Pharmacopsychiatry. 2006 Jul;39(4):152-4. https://www.ncbi.nlm.nih.gov/pubmed/16871471

 

How relevant are exercise capacity measures for evaluating treatment effects in chronic fatigue syndrome? Results from a prospective, multidisciplinary outcome study

Abstract:

OBJECTIVE: To evaluate the outcome of a multidisciplinary treatment programme for patients with chronic fatigue syndrome, including health-related quality of life (HRQoL) and psychosocial variables, and exercise capacity measures.

DESIGN: A six-month prospective outcome study.

SETTING: University outpatient rehabilitation clinic; group setting.

SUBJECTS: One hundred and sixteen women fulfilling chronic fatigue syndrome criteria.

INTERVENTIONS: Cognitive behaviourally and graded exercise-based strategies; emphasis on adaptive lifestyle changes.

MEASURES: Short Form General Health Survey (SF-36); Symptom Checklist (SCL-90); Causal Attribution List (CAL); Self-Efficacy Scale (SE); maximum progressive bicycle ergometer test with respiratory gas analysis; and isokinetic leg strength test, before and after treatment.

RESULTS: The total group significantly improved on nearly all reported HRQoL/psychosocial variables. Changes in exercise capacity measures were rather modest and did not correlate or only weakly correlated with HRQoL/psychosocial variables. Subgroup analyses indicated that less fit patients improved significantly more on exercise capacity measures than their more fit counterparts. Patients who were fitter at baseline scored better on pretreatment HRQoL/psychosocial variables, but both subgroups improved similarly on these variables.

CONCLUSIONS: Health-related quality of life and psychosocial functioning in patients with chronic fatigue syndrome improves after a six-month cognitive behaviourally and graded exercise-based multidisciplinary treatment programme. Increase in exercise capacity measures is not a necessary condition for reported improvements, except for less fit patients.

 

Source: Pardaens K, Haagdorens L, Van Wambeke P, Van den Broeck A, Van Houdenhove B. How relevant are exercise capacity measures for evaluating treatment effects in chronic fatigue syndrome? Results from a prospective, multidisciplinary outcome study. Clin Rehabil. 2006 Jan;20(1):56-66. https://www.ncbi.nlm.nih.gov/pubmed/16502751

 

Does methylphenidate reduce the symptoms of chronic fatigue syndrome?

Abstract:

PURPOSE: Chronic fatigue syndrome is a clinical entity consisting of prolonged and debilitating fatigue in which concentration disturbances are very frequent. Until now, no medical treatment has shown any efficacy. The objectives of this study were to investigate the short-term effects of methylphenidate, an amphetamine derivative, on fatigue, concentration disturbances, and quality of life.

SUBJECTS AND METHODS: A double-blind randomized placebo-controlled crossover study was conducted in 60 patients who fulfilled the 1994 Centers for Disease Control criteria for chronic fatigue syndrome and had concentration difficulties. Patients were enrolled between March 2003 and March 2004 at the outpatient department of a university hospital referral center for chronic fatigue syndrome patients. Random assignment to 4 weeks treatment with methylphenidate 2 x 10 mg/day, followed by 4 weeks of placebo treatment, or 4 weeks of placebo treatment, followed by methylphenidate treatment. Fatigue and concentration were measured with a Checklist Individual Strength (CIS) and a Visual Analogue Scale (VAS).

RESULTS: Fatigue scores fell significantly during methylphenidate intake in comparison with baseline (mean difference: -0.7, P = .010 for VAS; mean difference: -11.8, P <.0001 for CIS) and in comparison with placebo (mean difference: -1.0, P = .001 for VAS; mean difference: -9.7, P <.0001 for CIS). Concentration disturbances, measured with a VAS improved significantly under methylphenidate treatment compared with baseline (mean difference: -1.3, P <.0001) and compared with placebo (mean difference: -1.1, P <.0001). A clinical significant effect (> or =33% improvement or CIS < or =76) on fatigue was achieved in 17% of patients, who were considered responders; on concentration in 22% of patients.

CONCLUSIONS: Methylphenidate at a dose of 2 x 10 mg/day is significantly better than placebo in relieving fatigue and concentration disturbances in a minority of chronic fatigue syndrome patients. Further studies are needed to investigate the long-term effects of this treatment.

 

Source: Blockmans D, Persoons P, Van Houdenhove B, Bobbaers H. Does methylphenidate reduce the symptoms of chronic fatigue syndrome? Am J Med. 2006 Feb;119(2):167.e23-30. https://www.ncbi.nlm.nih.gov/pubmed/16443425

 

Treatment of chronic fatigue syndrome with antibiotics: pilot study assessing the involvement of Coxiella burnetii infection

Abstract:

OBJECTIVE: To examine whether Coxiella burnetii (C. burnetii) is involved in chronic fatigue syndrome (CFS), we administered tetracycline antibiotics to subjects with CFS, and followed changes in clinical symptoms, PCR findings, and C. burnetii antibody titers.

PATIENTS AND METHODS: The subjects were 8 patients with CFS and 213 with nonspecific complaints such as chronic fatigue and low-grade fever for several months or longer but not meeting the diagnostic criteria for CFS. All were examined for C. burnetii infection by nested PCR and the indirect immunofluorescence test (IF).

RESULTS: Four CFS patients (the CFS group) and 54 controls [the post-Q fever fatigue syndrome (QFS) group] positive for C. burnetii were treated mainly with minocycline or doxycycline (100 mg/day) for 3 months. After treatment, all 58 patients tested negative for C. burnetii infection. In the CFS group, no significant difference was noted between the mean pre- and post-treatment temperatures or headache scores. Similarly, there was no significant improvement in performance status (PS) scores. In the QFS group, however, mean temperatures and headache scores were significantly decreased after treatment (p<0.001). PS scores were also improved.

CONCLUSION: These results suggest the possibility of direct involvement of C. burnetii in the pathological state of CFS to be low, despite the C. burnetii infection rate being high in CFS patients. This is a pilot study and further larger investigations are necessary to confirm our preliminary results.

 

Source: Iwakami E1, Arashima Y, Kato K, Komiya T, Matsukawa Y, Ikeda T, Arakawa Y, Oshida S. Treatment of chronic fatigue syndrome with antibiotics: pilot study assessing the involvement of Coxiella burnetii infection. Intern Med. 2005 Dec;44(12):1258-63. https://www.ncbi.nlm.nih.gov/pubmed/16415546

 

Drug targets in stress-related disorders

Abstract:

Nervous and immune systems mutually cooperate via release of mediators of both neurological and immunological derivation. Adrenocorticotropin hormone (ACTH) is a product of the hypothalamus-pituitary adrenal axis (HPAA) which stimulates secretion of corticosteroids from adrenals. In turn, corticosteroids modulate the immune response in virtue of their anti-inflammatory activity.

On the other hand, catecholamines, products of the sympathetic nervous system (SNS), regulate immune function by acting on specific beta-adrenergic receptors. Conversely, cytokines released by monocytes/macrophages and lymphocytes, upon antigenic stimulation, are able to cross the blood-brain-barrier, thus modulating nervous functions (e.g., thermoregulation, sleep, and appetite). However, cytokines are locally produced in the brain, especially in the hypothalamus, thus contributing to the development of anorexic, pyrogenic, somnogenic and behavioural effects.

Besides pathogens and/or their products, the so-called stressors are able to activate both HPAA and SNS, thus influencing immune responses. In this respect, many studies conducted in medical students taking exams have evidenced an array of stress-induced immune alterations. Phobic disorders and migraine without aura (MWA) represent examples of stress-related disorders in which phagocytic immune deficits, endotoxemia and exaggerated levels of proinflammatory cytokines [Tumor Necrosis Factor-alpha (TNF- alpha), and interleukin- 1 beta] have been detected. Quite interestingly, administration of a thymic hormone could ameliorate clinical symptoms in phobic patients.

In MWA patients, a beta-blocker, propranolol, could mitigate migraine, whose cessation coincided with a drop of TNF-alpha serum concentration. In phobic disorders and in MWA, benzodiazepines are very often administered and, in this respect, some of them, such as diazepam, inhibit immune functions, while others, e.g., alprazolam, enhance immune responses. Alprazolam could improve clinical symptoms in MWA patients.

Chronic Fatigue Syndrome (CFS) is a disorder whose etiology and pathogenesis are still unknown. In this syndrome both abnormalities of nervous and immune systems have been reported. Despite many immune parameters evaluated in CFS no specific biomarkers of disease have been found. Our own data are in agreement with current literature in that we found decreased levels of serum (IFN)-gamma in these patients, thus indicating a predominance of T helper (h)1 response in CFS. Also leptin, a hormone which regulates food intake, fluctuates within normal ranges in CFS individuals. Quite interestingly, in depressed patients, used as controls, leptinaemia was more elevated than in CFS. Finally, in a series of recent therapeutic trials several immunomodulating agents have been used, such as staphypan Berna, lactic acid bacteria, kuibitang and intravenous immunoglobulin.

In conclusion, it seems that major drug targets in stress-related disorders are immune cells in terms of inhibition of proinflammatory cytokines and modulation of Th responses. In particular, according to recent evidences, antidepressants seem to exert beneficial effects in experimental autoimmune neuritis in rats by decreasing IFN- beta release or augmenting NK activity in depressed patients.

 

Source: Covelli V, Passeri ME, Leogrande D, Jirillo E, Amati L. Drug targets in stress-related disorders. Curr Med Chem. 2005;12(15):1801-9. http://www.ncbi.nlm.nih.gov/pubmed/16029148

 

Treatments for chronic fatigue syndrome

Abstract:

AIMS: To review studies evaluating the treatment of chronic fatigue and chronic fatigue syndrome, to describe predictors of response to treatment and to discuss the role of the occupational health physician.

METHODS: A literature search was carried out using Medline and PsychInfo.

RESULTS: Studies evaluating cognitive behaviour therapy, graded exercise therapy, pharmacological interventions (e.g. antidepressants and corticosteroids), immunological interventions and nutritional supplements were reviewed. The most promising results have been found with cognitive behaviour therapy and graded exercise therapy, and some predictors of outcome have been identified. Most of the other interventions were evaluated in just one or two studies and therefore evidence is insufficient to draw firm conclusions.

CONCLUSIONS: By applying the models of fatigue that form the bases for cognitive behaviour therapy and graded exercise therapy, occupational health physicians may play an important role in helping the patients with chronic fatigue syndrome to reduce their symptoms, improve their functioning and return to work.

 

Source: Rimes KA, Chalder T. Treatments for chronic fatigue syndrome. Occup Med (Lond). 2005 Jan;55(1):32-9. http://occmed.oxfordjournals.org/content/55/1/32.long (Full article)