Category: Treatment

Pharmacological treatment of chronic fatigue syndrome: focusing on the role of antidepressants

Abstract:

Chronic fatigue syndrome (CFS) is characterized by chronic, medically unexplained fatigue associated with effort- and stress-intolerance, widespread pain, and impairment in sleep and concentration. Although this constellation of symptoms is highly prevalent in clinical practice, the pathophysiological mechanisms underlying CFS are poorly understood. Current evidence indicates similarities in symptomatology, and possibly etiology and pathogenesis, between CFS and depression. Additionally, there is significant overlap between CFS and the syndrome of fibromyalgia for which antidepressants have shown consistent efficacy.

Data regarding antidepressant treatment of CFS is less copious and less uniformly positive, such that antidepressant use in CFS remains controversial. The current review aims to summarize available data related to antidepressants and other psychotropic agents in CFS to provide a platform for clinicians to make decisions in their treatment of this challenging syndrome.

We identified relevant studies through a PubMed literature search with a combination of the following search terms: ‘fatigue,’ ‘depression,’ ‘antidepressant,’ ‘etiology’ (e.g., ‘neurobiology,’ ‘neurotransmitter,’ ‘genetic’), ‘diagnosis,’ and ‘treatment’ (e.g., ‘antidepressant’ plus the specific name). In addition, studies were also identified via the reference sections of retrieved articles. The authors thoroughly reviewed major findings from the scanned literatures and eventually synthesized them, providing summary, interpretation, and future directions.

 

Source: Pae CU, Marks DM, Patkar AA, Masand PS, Luyten P, Serretti A. Pharmacological treatment of chronic fatigue syndrome: focusing on the role of antidepressants. Expert Opin Pharmacother. 2009 Jul;10(10):1561-70. Doi: 10.1517/14656560902988510. https://www.ncbi.nlm.nih.gov/pubmed/19514866

 

On the question of infectious aetiologies for multiple sclerosis, schizophrenia and the chronic fatigue syndrome and their treatment with antibiotics

Abstract:

Close similarities in the courses of multiple sclerosis and schizophrenia laid the theoretical ground for attempting to find a common infectious aetiology for the two diseases. Chlamydia pneumoniae, which belongs to the rickettsial family of microorganisms has been linked to both diseases. It is postulated that since rickettsial microorganisms are ubiquitous in human populations they and the human species normally live in peaceful coexistence. In rare cases, for unknown reasons, varieties of them may become aggressive and pathogenic.

The kynurenic acid hypothesis of schizophrenia has attracted much attention. It also seems to have initiated a paradigmatic shift from the hitherto prevailing serological research approach to one which focuses on immunological factors.

An open clinical pilot study in which, during 2006, eight female and five male patients with psychotic symptoms were treated with a combination of antibiotics is presented, to which, in the beginning of 2007 two female patients suffering from severe and long standing chronic fatigue syndrome were added. On one year follow-up, six out of the eight female patients showed stable excellent treatment results, whereas two were rated as showing significant treatment results. Four of the five men who entered the study were suffering from chronic schizophrenia, whereas the fifth, was a case of severe acute catatonic schizophrenia.

Two of the male patients showed significant treatment results, whereas three of them were rated as having had a slight to moderate improvement. No less than three of the women had suffered their first episode of psychosis after giving birth to their first (and only) child. This finding, as these women all responded excellently to treatment with antibiotics, indicates that post partum psychosis could be regarded as an infectious complication of childbirth of, as to the causative agent, unknown aetiology. High priority ought therefore be given to initiate controlled clinical trials with antibiotic treatment of this serious condition. The otherwise promising results of the pilot study seem to warrant further and controlled clinical trials with treatment with antibiotics of patients with psychotic symptoms.

As the second patient with psychotic symptoms to enter the study, had a long standing history of chronic fatigue, where an initial treatment with the antidepressant fluoxetine had only worsened her condition, whereas ninety days of treatment with antibiotics, combined with vitamin B injections, effected a complete recovery, the author decided, when two patients with long standing and incapacitating chronic fatigue syndromes sought the clinic in February and March 2007, to include them in the study. The first of them, after sixty days of treatment with antibiotics showed excellent treatment results on follow-up one year later, whereas the second, who also took the combination of antibiotics for sixty days, was rated as having shown a significant improvement.

Comment in: Hypotheses concerning rickettsial microorganisms, autoimmune diseases and new treatment strategies. [Med Hypotheses. 2010]

 

Source: Frykholm BO. On the question of infectious aetiologies for multiple sclerosis, schizophrenia and the chronic fatigue syndrome and their treatment with antibiotics. Med Hypotheses. 2009 Jun;72(6):736-9. doi: 10.1016/j.mehy.2008.11.045. Epub 2009 Mar 6. https://www.ncbi.nlm.nih.gov/pubmed/19269110

 

Protective effects of antidepressants against chronic fatigue syndrome-induced behavioral changes and biochemical alterations

Abstract:

Chronic fatigue syndrome (CFS) is characterized by profound fatigue, which substantially interferes with daily activities. The aim of this study was to explore the protective effects of antidepressants in an animal model of CFS in mice. Male albino mice were forced to swim individually for a period of 6-min session each for 7 days. Imipramine (10 and 20 mg/kg), desipramine (10 and 20 mg/kg) and citalopram (5 and 10 mg/kg) were administered 30 min before forced swimming test on each day.

Various behavior tests (immobility time, locomotor activity, anxiety-like behavior by plus maze and mirror chamber) followed by biochemical parameters (lipid peroxidation, reduced glutathione, catalase and nitrite level) were assessed in chronic stressed mice. Chronic forced swimming for 7 days significantly caused increase in immobility period, impairment in locomotor activity, anxiety-like behavior, and oxidative stress (raised lipid peroxidation, nitrite activity and reduced glutathione and catalase activity) as compared with naïve mice (P < 0.05).

Seven days of pretreatment with imipramine (10 and 20 mg/kg), desipramine (10 and 20 mg/kg), and citalopram (5 and 10 mg/kg) significantly reduced immobility time, improved locomotor activity and anti-anxiety effect (in both plus maze and mirror chamber test), and attenuated oxidative stress in chronic stressed mice as compared with control (chronic fatigues) (P < 0.05). These results suggested that these drugs have protective effect and could be used in the management of chronic fatigue like conditions.

 

Source: Kumar A, Garg R. Protective effects of antidepressants against chronic fatigue syndrome-induced behavioral changes and biochemical alterations. Fundam Clin Pharmacol. 2009 Feb;23(1):89-95. doi: 10.1111/j.1472-8206.2008.00638.x. Epub 2009 Jan 10. https://www.ncbi.nlm.nih.gov/pubmed/19207541

 

Customizing treatment of chronic fatigue syndrome and fibromyalgia: the role of perpetuating factors

Erratum in: Psychosomatics. 2009 Mar-Apr;50(2):176.

Abstract:

BACKGROUND: Syndromes characterized by chronic, medically unexplained fatigue, effort- and stress-intolerance, and widespread pain are highly prevalent in medicine.

RESULTS: In chronic fatigue syndrome (CFS) and fibromyalgia (FM), various perpetuating factors may impair patients’ quality of life and functioning and impede recovery. Although cognitive-behavioral and graded-exercise therapy are evidence-based treatments, the effectiveness and acceptability of therapeutic interventions in CFS/FM may largely depend on a customized approach taking the heterogeneity of perpetuating factors into account.

CONCLUSION: Further research should clarify the aim and outcome of different treatment strategies in CFS/FM, as well as the underlying mechanisms of change, including those facilitating neurobiological recovery.

 

Source: Van Houdenhove B, Luyten P. Customizing treatment of chronic fatigue syndrome and fibromyalgia: the role of perpetuating factors. Psychosomatics. 2008 Nov-Dec;49(6):470-7. doi: 10.1176/appi.psy.49.6.470. https://www.ncbi.nlm.nih.gov/pubmed/19122123

 

Diagnostic and treatment challenges of chronic fatigue syndrome: role of immediate-release methylphenidate

Abstract:

Chronic fatigue syndrome (CFS) is a distinct entity belonging to the group of persistent fatigue that can be challenging to diagnose and to treat. It is characterized by a combination of prolonged fatigue, other nonspecific somatic manifestations and neuropsychological symptoms, including difficulties with concentration, short-term memory and thinking, as well as impaired attention and slowed processing speed. Neurostimulants increasing dopamine and norepinephrine activity, such as bupropion, dextroamphetamine and recently immediate-release methylphenidate have been advocated to improve neurocognitive deficits. The use of immediate-release methylphenidate in CFS has been shown in one small study. Using the positive results of this study and the well-known beneficial effects of the drug on a range of similar cognitive symptoms in attention-deficit/hyperactivity disorder, this perspective addresses CFS and other related disorders and provides a discussion on the potential promising role of methylphenidate in the therapeutic armamentarium of CFS.

 

Source: Valdizán Usón JR, Idiazábal Alecha MA. Diagnostic and treatment challenges of chronic fatigue syndrome: role of immediate-release methylphenidate. Expert Rev Neurother. 2008 Jun;8(6):917-27. Doi: 10.1586/14737175.8.6.917. https://www.ncbi.nlm.nih.gov/pubmed/18505357

 

Cognitive-behavioural therapy v. mirtazapine for chronic fatigue and neurasthenia: randomised placebo-controlled trial

Abstract:

BACKGROUND: Single interventions in chronic fatigue syndrome have shown only limited effectiveness, with few studies of comprehensive treatment programmes.

AIMS: To examine the effect of a comprehensive cognitive-behavioural treatment (CCBT) programme compared with placebo-controlled mirtazapine medication in patients with chronic fatigue, and to study the effect of combined medication and CCBT.

METHOD: A three-armed randomised clinical trial of mirtazapine, placebo and a CCBT programme was conducted to investigate treatment effect in a patient group (n=72) with chronic fatigue referred to a specialist clinic. The CCBT programme was compared with mirtazapine or placebo therapy for 12 weeks, followed by 12 weeks treatment with a mixed crossover-combination design. Assessments were done at 12 weeks and 24 weeks.

RESULTS: By 12 weeks the treatment effect was significantly better in the group initially receiving CCBT, as assessed with the Fatigue Scale (P=0.014) and the Clinical Global Impression Scale (P=0.001). By 24 weeks the treatment group initially receiving CCBT for 12 weeks followed by mirtazapine for 12 weeks showed significant improvement compared with the other treatment groups on the Fatigue Scale (P<0.001) and the Clinical Global Impression Scale (P=0.002). Secondary outcome measures showed overall improvement with no significant difference between treatment groups.

CONCLUSIONS: Multimodal interventions may have positive treatment effects in chronic fatigue syndrome. Sequence of interventions seem to be of importance.

 

Source: Stubhaug B, Lie SA, Ursin H, Eriksen HR. Cognitive-behavioural therapy v. mirtazapine for chronic fatigue and neurasthenia: randomised placebo-controlled trial. Br J Psychiatry. 2008 Mar;192(3):217-23. doi: 10.1192/bjp.bp.106.031815. http://bjp.rcpsych.org/content/192/3/217.long (Full article)

 

Rehabilitation of decreased motor performance in patients with chronic fatigue syndrome: should we treat low effort capacity or reduced effort tolerance?

Abstract:

AIM: The aetiology, pathophysiology, diagnostic delineation and treatment of chronic fatigue syndrome (CFS) remain a matter of debate. Here some aspects of the debate are elucidated, with a particular focus on the patients’ decreased motor performance.

HYPOTHESIS: The pathophysiological basis of decreased motor performance in CFS may, theoretically, involve three components: (1) a peripheral energetic deficit (impaired oxidative metabolism and/or physical deconditioning); (2) a central perceptual disturbance (higher effort sense or increased ‘interoception’); and (3) a fundamental failure of the neurobiological stress system, leading to an abnormal ‘sickness response’. It is proposed that the first two components may lead to low effort capacity, while the third component may lead to reduced effort tolerance. Although there is evidence for low effort capacity influencing symptoms and functional limitations in CFS, it is assumed that reduced effort tolerance might be the primary disturbance in CFS.

DIAGNOSTIC IMPLICATIONS: Distinguishing low effort capacity and reduced effort tolerance may contribute to a refinement of current diagnostic criteria of CFS and the identification of subgroups.

THERAPEUTIC IMPLICATIONS: The above-mentioned distinction may make it possible to formulate a rationale for an effective implementation and adequate outcome evaluation of rehabilitation strategies in CFS.

RESEARCH IMPLICATIONS: This new heuristic framework may inform future research aimed at disentangling the complex determination of impaired motor performance in CFS, as well as studies aimed at customizing treatment to different subtypes of patients.

 

Source: Van Houdenhove B, Verheyen L, Pardaens K, Luyten P, Van Wambeke P. Rehabilitation of decreased motor performance in patients with chronic fatigue syndrome: should we treat low effort capacity or reduced effort tolerance? Clin Rehabil. 2007 Dec;21(12):1121-42. https://www.ncbi.nlm.nih.gov/pubmed/18042608

 

Open-label study of s-citalopram therapy of chronic fatigue syndrome and co-morbid major depressive disorder

Abstract:

OBJECTIVE: Chronic fatigue syndrome (CFS) is a debilitating disorder with prominent symptoms of malaise, fatigue, myalgia, arthralgia, and impaired concentration. The symptoms of CFS may often overlap those of Major Depressive Disorder (MDD). Treatment of CFS has generally been disappointing. We hypothesized that s-citalopram therapy may improve the symptoms of both disorders in CFS patients with co-morbid depression.

METHODS: 16 patients received s-citalopram 10 mg to 20 mg daily for up to 12 weeks. Outcome measures of CFS included the Chalder Fatigue Questionnaire (CFQ), the multi-dimensional Fatigue Impact Scale (FIS), the CFS symptom rating (CFS-SR) 100 mm visual analogue scale, and the clinical global impressions severity (CGI/S) and change (CGI/C) ratings. Secondary outcomes of MDD included the Hamilton Depression Rating (HAM-D), Beck Depression Inventory (BDI), and the CGI/S and CGI/C ratings of MDD.

RESULTS: We observed reductions in the mean CFQ score (p<0.0005), FIS score (p<0.0005), and CGI/S (p<0.0005) and CGI/C (p<0.0005) ratings over time. There was a significant improvement in 5 of the 8 CFS-SR symptoms: post-exertion malaise (p=0.001), headaches (p<0.0005), un-refreshing sleep (p<0.0005), and impaired memory and concentration (p<0.0005). There was also a reduction in mean HAM-D (p<0.0005), BDI (p<0.0005), CGI/S (p=0.001) and CGI/C (p<0.0005) ratings of MDD.

LIMITATIONS: The sample size was limited and the study design was not double-blind or placebo controlled.

CONCLUSION: We observed a significant reduction in both CFS and co-morbid MDD symptom severity ratings, and improvement in 5 of 8 core somatic symptoms of CFS during s-citalopram therapy.

 

Source: Amsterdam JD, Shults J, Rutherford N. Open-label study of s-citalopram therapy of chronic fatigue syndrome and co-morbid major depressive disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2008 Jan 1;32(1):100-6. Epub 2007 Aug 3. https://www.ncbi.nlm.nih.gov/pubmed/17804135

 

Considerations for the treatment of chronic fatigue syndrome

Abstract:

The etiology of chronic fatigue syndrome(CFS) is still unknown and under active discussion, but involvement of psychosocial factors appear to be essential for the onset and clinical course of CFS. As CFS patients complain of many stress-related physical and psychological symptom, it is important to understand the CFS from psychosomatic point of view. Not only for the pharmaceutical treatment, attentive consideration is required for treatment of exhaustion of body and mind of CFS patients. Use of anti-depressants or oriental herb medicine is often effective to relieve the anxiety and depressive condition. Furthermore to augment the self-healing potential, psychosomatic approach is important to modify the life style and behavioral characteristics.

 

Source: Murakami M. Considerations for the treatment of chronic fatigue syndrome. Nihon Rinsho. 2007 Jun;65(6):1089-92. [Article in Japanese] https://www.ncbi.nlm.nih.gov/pubmed/17561702

 

Treatment of chronic fatigue and orthostatic intolerance with propranolol

Abstract:

We describe the effect of propranolol in an adolescent with chronic fatigue syndrome and orthostatic intolerance. Our observations suggest that the head-up tilt-test and beta-blocker treatment might be considered in patients with chronic fatigue syndrome and that enhanced sympathetic nervous activity might be part of the underlying pathophysiology.

 

Source: Wyller VB, Thaulow E, Amlie JP. Treatment of chronic fatigue and orthostatic intolerance with propranolol. J Pediatr. 2007 Jun;150(6):654-5. https://www.ncbi.nlm.nih.gov/pubmed/17517256