Randomised, double-blind, placebo-controlled study of fluoxetine in chronic fatigue syndrome

Abstract:

BACKGROUND: No somatic treatment has been found to be effective for chronic fatigue syndrome (CFS). Antidepressant therapy is commonly used. Fluoxetine is recommended in preference to tricyclic agents because it has fewer sedative and autonomic nervous system effects. However, there have been no randomised, placebo-controlled, double-blind studies showing the effectiveness of antidepressant therapy in CFS. We have carried out such a study to assess the effect of fluoxetine in depressed and non-depressed CFS patients.

METHODS: In this randomised, double-blind study, we recruited 44 patients to the depressed CFS group, and 52 to the non-depressed CFS group. In each group participants were randomly assigned to receive either fluoxetine (20 mg once daily) or placebo for 8 weeks. The effect of fluoxetine was assessed by questionnaires, self-observation lists, standard neuropsychological tests, and a motion-sensing device (Actometer), which were applied on the day treatment started and on the last day.

FINDINGS: The two groups were well matched in terms of age, sex distribution, employment and marital status, and duration of CFS. There were no significant differences between the placebo and fluoxetine-treated groups in the change during the 8-week treatment period for any dimension of CFS. There was no change in subjective assessments of fatigue, severity of depression, functional impairment, sleep disturbances, neuropsychological function, cognitions, or physical activity in the depressed or the non-depressed subgroup.

INTERPRETATION: Fluoxetine in a 20 mg daily dose does not have a beneficial effect on any characteristic of CFS. The lack of effect of fluoxetine on depressive symptoms in CFS suggests that processes underlying the presentation of depressive symptoms in CFS may differ from those in patients with major depressive disorder.

 

Source: Vercoulen JH, Swanink CM, Zitman FG, Vreden SG, Hoofs MP, Fennis JF, Galama JM, van der Meer JW, Bleijenberg G. Randomised, double-blind, placebo-controlled study of fluoxetine in chronic fatigue syndrome. Lancet. 1996 Mar 30;347(9005):858-61. http://www.ncbi.nlm.nih.gov/pubmed/8622391

 

Neurocognitive functioning in chronic fatigue syndrome

Abstract:

Although substantial research has been conducted on chronic fatigue syndrome (CFS) over the past decade, the syndrome remains poorly understood. The most recent case definition describes CFS as being characterized both by disabling fatigue and by subjective reports of difficulty with concentration and “short-term” memory. However, research into the neurocognitive and psychological functioning of individuals with CFS has provided mixed objective results. The current paper reviews studies that have examined the neurocognitive and/or psychological functioning of individuals with CFS. Changes in research design and instruments employed to study individuals with CFS are suggested.

 

Source: DiPino RK, Kane RL. Neurocognitive functioning in chronic fatigue syndrome. Neuropsychol Rev. 1996 Mar;6(1):47-60. http://www.ncbi.nlm.nih.gov/pubmed/9144668

 

Screening for psychiatric morbidity in subjects presenting with chronic fatigue syndrome

Abstract:

BACKGROUND: There is a need for a valid self-rating questionnaire to screen for psychiatric morbidity in patients with chronic fatigue syndrome (CFS). This study had the aim of assessing the utility and validity of two commonly used measures.

METHOD: Scores obtained on the General Health Questionnaire (GHQ) and the Beck Depression Inventory (BDI) were compared with various diagnostic and severity ratings obtained via a validating clinical interview, the Schedules for the Clinical Assessment of Neuropsychiatry (SCAN) in 95 consecutively referred subjects at a medical out-patient clinic who fulfilled standard criteria for CFS, and 48 healthy controls. Outcome measures were validating coefficients and receiver operating characteristics (ROC) for different thresholds and scoring on GHQ and BDI and index of definition (ID) as measured by SCAN; and Pearson and point by serial correlation coefficients for different diagnostic groups derived via SCAN and defined according to ICD-10 and DSM-III-R.

RESULTS: GHQ and BDI perform poorly as screeners of psychiatric morbidity in CFS subjects when compared with various SCAN derived ratings although results for controls are comparable with other studies.

CONCLUSIONS: Neither the GHQ nor BDI alone can be recommended as screeners for psychiatric morbidity in CFS subjects.

 

Source: Farmer A, Chubb H, Jones I, Hillier J, Smith A, Borysiewicz L. Screening for psychiatric morbidity in subjects presenting with chronic fatigue syndrome. Br J Psychiatry. 1996 Mar;168(3):354-8. http://www.ncbi.nlm.nih.gov/pubmed/8833692

 

Fibromyalgia, chronic fatigue syndrome, and myofascial pain

Abstract:

The prevalence of fibromyalgia in the general population was found to be 2% and increased with age. Multiple traumatic factors, including sexual and physical abuse, may be important initiating events. The most important pathophysiologic studies in fibromyalgia included evidence of altered blood flow to the brain and hypothalamic-pituitary-adrenal dysfunction. The prevalence of chronic fatigue syndrome is much less than that of fibromyalgia. Epidemiologic studies demonstrated that chronic fatigue and symptoms of fibromyalgia are distributed as continuous variables in the general population. No association between chronic fatigue and initial infections was seen in primary care practices.

 

Source: Goldenberg DL. Fibromyalgia, chronic fatigue syndrome, and myofascial pain. Curr Opin Rheumatol. 1996 Mar;8(2):113-23. http://www.ncbi.nlm.nih.gov/pubmed/8732795

 

Hypochondriasis influences quality-of-life outcomes in patients with chronic fatigue

Abstract:

BACKGROUND: To determine how hypochondriacal symptoms influence the quality-of-life outcomes of patients with a chief complaint of chronic fatigue.

METHODS: Cross-sectional cohort study of a consecutive sample of 71 patients (mean duration of fatigue of 4.1 years). Forty-eight (68%) patients met criteria for current major depression and 32 (45%) met criteria for chronic fatigue syndrome (CFS). All patients received a comprehensive medical and psychiatric evaluation. Quality-of-life and physical, depressive and hypochondriacal symptom scores were assessed through reliable self-report questionnaires and a structured interview. A path model expressing the relation between predictor variables (hypochondriasis and depression), intervening variables (physical symptoms) and quality of life was postulated and evaluated using structural equation methods.

RESULTS: The paths linking hypochondriasis with physical symptoms and mental health and the path connecting physical symptoms and quality of life were each statistically significant. The model applied especially well to patients who fulfilled CFS criteria.

CONCLUSIONS: The quality of life of chronic fatigue patients correlates with the severity of their physical symptoms and their hypochondriacal disposition toward illness.

 

Source: Manu P, Affleck G, Tennen H, Morse PA, Escobar JI. Hypochondriasis influences quality-of-life outcomes in patients with chronic fatigue. Psychother Psychosom. 1996 Mar-Apr;65(2):76-81. http://www.ncbi.nlm.nih.gov/pubmed/8711085

 

An assessment of cognitive function and mood in chronic fatigue syndrome

Abstract:

Data were gathered regarding the associates of chronic fatigue syndrome (CFS) with: (1) speed of cognitive processing, (2) motor speed, (3) ability to sustain attention, and (4) mood. Patients were given a brief neuropsychological test battery before and after double-blind treatment with terfenadine or placebo and completed a daily mood rating scale (Positive and Negative Affect Schedule) during the study.

CFS patients exhibited slower cognitive processing and motor speed and lower positive affect, as compared to data reported from previous studies of healthy subjects and other patient groups; however, CFS patients did not exhibit deficits in sustained attention in comparison to other groups.

The CFS patients’ ability to attend to verbal versus figural stimuli and mood ratings were different from those reported in studies of patients with depression. Because of methodological limitations, these findings are preliminary, but they encourage further assessment of cognitive dysfunction and mood in CFS.

 

Source: Marshall PS, Watson D, Steinberg P, Cornblatt B, Peterson PK, Callies A, Schenck CH. An assessment of cognitive function and mood in chronic fatigue syndrome. Biol Psychiatry. 1996 Feb 1;39(3):199-206. http://www.ncbi.nlm.nih.gov/pubmed/8837981

 

Eosinophil cationic protein serum levels and allergy in chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is a syndrome of uncertain etiopathogenesis characterized by disabling fatigue associated with a variable number of somatic and/or neuropsychologic symptoms. In patients with CFS, several immunologic abnormalities can be detected, including a higher prevalance of allergy.

The aim of this study was to determine whether CFS patients, well studied for their allergy profile, show signs of eosinophil activation, as detectable by the measurement in serum of eosinophil cationic protein (ECP) levels. In 35 consecutive CFS outpatients (diagnosis based on the Centers for Disease Control case definition), ECP was measured in serum by a competitive enzyme immunoassay (ECP-FEIA kit, Kabi Pharmacia Diagnostics, Uppsala, Sweden).

Fourteen disease-free subjects with no history of CFS or allergy were selected as controls. ECP serum levels were significantly higher in CFS patients than in controls (18.0 +/- 11.3 micrograms/l vs 7.3 +/- 2.1 micrograms/l; P < 0.01). In the CFS population, the prevalence of RAST positivity to one or more allergens was 77%, while no control showed positive RAST.

Twelve of the 14 CFS patients with increased ECP serum levels were RAST-positive. However, CFS RAST-positive patients had no significantly higher ECP serum levels than CFS RAST-negative patients (19.3 +/- 12.4 micrograms/l vs 13.6 +/- 3.7 micrograms/l; P = 0.4).

This is the first report of increased serum levels of ECP in CFS. On the basis of the available data, it is discussed whether eosinophil activation has a pathogenetic role in CFS or is linked to the frequently associated allergic condition, or, finally, whether a common immunologic background may exist for both atopy and CFS.

 

Source: Conti F, Magrini L, Priori R, Valesini G, Bonini S. Eosinophil cationic protein serum levels and allergy in chronic fatigue syndrome. Allergy. 1996 Feb;51(2):124-7. http://www.ncbi.nlm.nih.gov/pubmed/8738520

 

Brainstem hypoperfusion in CFS

Comment on: Brainstem perfusion is impaired in chronic fatigue syndrome. [QJM. 1995]

 

Sir, Costa and his colleagues {QJ Med 1995; 88:767-73) are to be congratulated for providing more information about chronic fatigue syndrome. Hypocapnia is a powerful and readily available cerebral vasoconstrictor.1

The ‘cerebral vasoconstriction, and reduction in cerebral blood flow, are initiated when the arterial pCO2 has fallen 2 mmHg below normal. When the pCO2 has fallen by 25 mmHg, cerebral blood flow is decreased by about one third … the maximum possible reduction of blood flow that can be achieved by respiratory alkalaemia is of the order of 40 per cent’.2

You can read the rest of this comment here: http://qjmed.oxfordjournals.org/content/89/2/163.1.long

 

Source: Nixon PG. Brainstem hypoperfusion in CFS. QJM. 1996 Feb;89(2):163-4. http://qjmed.oxfordjournals.org/content/89/2/163.1.long

 

Management of chronic fatigue syndrome: case study

Abstract:

1. Chronic fatigue syndrome (CFS) is a complex disorder marked by incapacitating fatigue of uncertain etiology which has resulted in a least a 50% reduction in activity and is of at least 6 months’ duration. 2. Definitive diagnosis can be very challenging. Because no markers objectively identify the presence of CFS, diagnosis depends heavily on the presence of subjective complaints. 3. The current philosophy of CFS management is to use a multidisciplinary approach incorporating these rehabilitation goals: restore a sense of self efficacy and control; gradually increase physical activity; and decrease the restrictions imposed by CFS.

 

Source: Dyck D, Allen S, Barron J, Marchi J, Price BA, Spavor L, Tateishi S. Management of chronic fatigue syndrome: case study. AAOHN J. 1996 Feb;44(2):85-92. http://www.ncbi.nlm.nih.gov/pubmed/8694980

 

The rise and fall of the chronic fatigue syndrome as defined by Holmes et al.

Abstract:

This paper is a sequel to my monograph on neurocirculatory asthenia and chronic fatigue syndrome. It pays special attention to the nature of chronic fatigue syndrome, to the forms of neurocirculatory asthenia, and above all to the 6th form in which profound fatigue is the dominant symptom. All forms including the 6th are characterized by the presence of concomitant symptoms due to dysfunction of the autonomic nervous system. Chronic fatigue syndrome as defined by Holmes et al is devoid of these symptoms. Up till the present day no case histories of it have been published. It is argued that chronic fatigue syndrome sensu Holmes et al does not exist, the 6th form of neurocirculatory asthenia having to take up its place.

 

Source: van Waveren EK. The rise and fall of the chronic fatigue syndrome as defined by Holmes et al. Med Hypotheses. 1996 Feb;46(2):63-6. http://www.ncbi.nlm.nih.gov/pubmed/8692045