Treatment – Page 12 – American ME and CFS Society

α-1 antitrypsin and chronic fatigue syndrome: a case study from pathophysiology to clinical practice

Abstract:

SUMMARY

BACKGROUND: Several lines of evidence support the involvement of inflammatory and immunologic abnormalities in chronic fatigue syndrome (CFS). Since recent studies have shown that α-1 antitrypsin (AAT) possesses anti-inflammatory properties, the potential therapeutic effect of AAT treatment on CFS has been investigated.

CASE PRESENTATION: A 49-year-old woman diagnosed with CFS was treated with intravenous infusions of a human plasma-derived AAT concentrate (60 mg/kg body weight weekly for 8 consecutive weeks). The patient’s monocyte elastase, a regulator of inflammatory processes, was 1170 U/mg. At completion of treatment, improvement in maximal workload was observed (54.0-71.7% of predicted). Additionally, amelioration in working memory (scores: 83-94) and perceptual organization (scores: 75-83) were detected on the Wechsler Adult Intelligence Scale-III test. Monocyte elastase decreased to a normal range (<150 U/mg). Improvement in functional capacity allowed the patient to work in part-time employment.

CONCLUSION: These findings suggest a possible role for AAT in the treatment of CFS.

Source: Alegre J, Camprubí S, García-Quintana A. α-1 antitrypsin and chronic fatigue syndrome: a case study from pathophysiology to clinical practice.Pain Manag. 2013 Mar;3(2):119-22. doi: 10.2217/pmt.12.84. https://www.ncbi.nlm.nih.gov/pubmed/24645995

Agomelatine but not melatonin improves fatigue perception: a longitudinal proof-of-concept study

Abstract:

Chronic Fatigue Syndrome (CFS) represents a disabling condition characterized by persistent mental and physical fatigue, bodily discomfort and cognitive difficulties. To date the neural bases of CFS are poorly understood; however, mono-aminergic abnormalities, sleep-wake cycle changes and prefrontal dysfunctions are all thought to play a role in the development and maintenance of this condition.

Here we explored in a group of 62 CFS subjects the impact on fatigue levels of agomelatine, an antidepressant with agonist activity at melatonin receptors (MT1 and MT2) and antagonist activity at serotoninergic 2C receptors (5HT2C). To tease out the relative effects of MT-agonism and 5HT2C antagonism on fatigue, we compared agomelatine 50mg u.i.d. with sustained release melatonin 10mg u.i.d. in the first 12-week-long phase of the study, and then switched all melatonin-treated subjects to agomelatine in the second 12-week-long phase of the study.

Agomelatine treatment, but not melatonin, was associated with a significant reduction of perceived fatigue and an increase in perceived quality of life. Moreover the switch from melatonin to agomelatine was associated with a reduction of fatigue levels. Agomelatine was well tolerated by all enrolled subjects. Our data, albeit preliminary, suggest that agomelatine treatment could represent a novel useful approach to the clinical care of subjects with CFS.

Source: Pardini M, Cordano C, Benassi F, Mattei C, Sassos D, Guida S, Serrati C, Primavera A, Amore M, Cocito L, Emberti Gialloreti L. Agomelatine but not melatonin improves fatigue perception: a longitudinal proof-of-concept study. Eur Neuropsychopharmacol. 2014 Jun;24(6):939-44. doi: 10.1016/j.euroneuro.2014.02.010. Epub 2014 Feb 25. https://www.ncbi.nlm.nih.gov/pubmed/24636462

Valacyclovir treatment of chronic fatigue in adolescents

Abstract:

Chronic fatigue syndrome (CFS) presents with fatigue, low motivation, diminished mood, and reduced activity, all symptoms having extensive diagnostic overlaps with depression. Studies have linked chronic viral infections with CFS, and antiviral therapy has effectively treated CFS in adult patients.

In a retrospective case series, 15 adolescents and preteens referred to the author for treatment-resistant depression or mood disorder were evaluated and found to have met the Fukuda diagnostic criteria for CFS. While a subset (4/15) had been diagnosed in the past with CFS, the majority had a current diagnosis of depression or a mood disorder. The Diagnostic and Statistical Manual-IV Text Revision (DSM-IV TR) criteria for depression were not met in all patients, although 3 cases of mood disorder not otherwise specified (MD-NOS) and 1 case of Tourette syndrome (TS) plus MD-NOS were diagnosed. Baseline scores on the Children’s Depression Inventory (CDI) were below the cutoff for depression in all but 1 patient. Baseline self-assessment scales for CFS or fatigue were obtained and sleep was evaluated with sleep logs.

All patients were treated subsequently with valacyclovir, with 93% having a positive response. At the end of treatment, scores on fatigue self-assessment scales improved significantly (P < .001). Vigor subscale scores also improved significantly (P < .001). Some patients experienced complete resolution of symptoms. Although not every patient was tested, available laboratory testing revealed increased counts of natural killer (NK) cells and decreased human herpesvirus 6 (HHV-6) antibody titers in all patients who responded to valacyclovir.

This article discusses the significance of infectious agents in the pathogenesis of psychiatric symptoms. The study’s data support an intriguing hypothesis that a portion of treatment-resistant depression in fact may be undiagnosed CFS or other chronic viral infection.

Source: Henderson TA. Valacyclovir treatment of chronic fatigue in adolescents. Adv Mind Body Med. 2014 Winter;28(1):4-14. https://www.ncbi.nlm.nih.gov/pubmed/24445302

Treatment of 741 Italian patients with chronic fatigue syndrome

Abstract:

BACKGROUND: Chronic Fatigue Syndrome (CFS) is a distinctive syndrome characterized by specific symptoms cluster. CFS mostly affects women and often results in severe functional limitation. Its prevalence varies from 0.4 to 2.5% in the general population. In our prior studies on the clinical features of 205 CFS patients we founded immunological and brain abnormalities. In this paper we illustrate our caseload on CFS treatment.

PATIENTS AND METHODS: From January 2000 to December 2005, we evaluated all the patients admitted at the CFS Unit of the Aviano National Cancer Institute, for staging procedures and treatments. Patients not meeting the Fukuda diagnostic criteria were excluded.

RESULTS: 250 male and 491 female (median age 35.5 and 39.3 years, respectively) were enrolled and treated for CFS. As expected, CFS resulted from previous infectious disease in all patients. Female patients showed to be more affected by symptoms than male patients. The treatment schedules followed by the patients included nutritional supplements alone, corticosteroids, antidepressant/sedative drugs, and antiviral/immunoglobulin drugs. Antiviral/ immunoglobulin drugs achieved the best response (15.3% positive responses vs. 8.3% negative responses; OR 0.44, CI 0.26-0.74, p = 0.002). The carrying out of 4 or more treatments showed a protective effect (OR 0.46, CI 0.28-0.77, p = 0.003). This finding was confirmed in the multivariate analysis, adjusted by type of drugs (OR 0.49, CI 0.28-0.84, p = 0.009) and number of treatments carried out (OR 0.51, CI 0.30-0.86, p = 0.01); these two variables were independent.

CONCLUSIONS: These findings show that the antiviral/immunoglobulin approach has a longer positive disease free survival in comparison with other approaches. However, CFS still remains a difficult disease to be effectively treated.

Source: Tirelli U, Lleshi A, Berretta M, Spina M, Talamini R, Giacalone A. Treatment of 741 Italian patients with chronic fatigue syndrome. Eur Rev Med Pharmacol Sci. 2013 Nov;17(21):2847-52. http://www.europeanreview.org/article/5782 (Full article available as PDF)

Randomized clinical trial to evaluate the efficacy and safety of valganciclovir in a subset of patients with chronic fatigue syndrome

Abstract:

There is no known treatment for chronic fatigue syndrome (CFS). Little is known about its pathogenesis. Human herpesvirus 6 (HHV-6) and Epstein-Barr virus (EBV) have been proposed as infectious triggers.

Thirty CFS patients with elevated IgG antibody titers against HHV-6 and EBV were randomized 2:1 to receive valganciclovir (VGCV) or placebo for 6 months in a double-blind, placebo-controlled trial. Clinical endpoints aimed at measuring physical and mental fatigue included the Multidimensional Fatigue Inventory (MFI-20) and Fatigue Severity Scale (FSS) scores, self-reported cognitive function, and physician-determined responder status. Biological endpoints included monocyte and neutrophil counts and cytokine levels.

VGCV patients experienced a greater improvement by MFI-20 at 9 months from baseline compared to placebo patients but this difference was not statistically significant. However, statistically significant differences in trajectories between groups were observed in MFI-20 mental fatigue subscore (P = 0.039), FSS score (P = 0.006), and cognitive function (P = 0.025). VGCV patients experienced these improvements within the first 3 months and maintained that benefit over the remaining 9 months. Patients in the VGCV arm were 7.4 times more likely to be classified as responders (P = 0.029). In the VGCV arm, monocyte counts decreased (P < 0.001), neutrophil counts increased (P = 0.037) and cytokines were more likely to evolve towards a Th1-profile (P < 0.001). Viral IgG antibody titers did not differ between arms.

VGCV may have clinical benefit in a subset of CFS patients independent of placebo effect, possibly mediated by immunomodulation and/or antiviral effect. Further investigation with longer treatment duration and a larger sample size is warranted.

TRIAL REGISTRATION: ClinicalTrials.gov NCT00478465.

Source: Montoya JG, Kogelnik AM, Bhangoo M, Lunn MR, Flamand L, Merrihew LE, Watt T, Kubo JT, Paik J, Desai M. Randomized clinical trial to evaluate the efficacy and safety of valganciclovir in a subset of patients with chronic fatigue syndrome. J Med Virol. 2013 Dec;85(12):2101-9. doi: 10.1002/jmv.23713. Epub 2013 Aug 19. https://www.ncbi.nlm.nih.gov/pubmed/23959519

Article on CFS does not reflect current best treatment practices

TO THE EDITOR: We feel that the overview of the diagnosis and treatment of chronic fatigue syndrome (CFS) was incomplete and did not reflect current best treatment practices. The discussion of current CFS research omitted key studies, such as evidence from prospective cohort studies indicating that up to 10 percent of patients with postinfectious syndromes develop CFS, regardless of the type of infectious agent.1 Biomarker research has shown distinct patterns of gene expression correlating with cytokine, adrenergic, and sensory receptor changes after modest exercise in patients with CFS compared with healthy sedentary patients.2 Indeed, many peer-reviewed publications support a physiologic etiology of CFS.

You can read the rest of this comment here: http://www.aafp.org/afp/2013/0401/ol1.html

Comment on: Chronic fatigue syndrome: diagnosis and treatment. [Am Fam Physician. 2012]

Source: Bateman L, Spotila J. Article on CFS does not reflect current best treatment practices. Am Fam Physician. 2013 Apr 1;87(7):Online. http://www.aafp.org/afp/2013/0401/ol1.html (Full article)

Treating chronic fatigue syndrome – a study into the scientific evidence for pharmacological treatments

Abstract:

BACKGROUND: Chronic fatigue syndrome, or myalgic encephalomyelitis (CFS), is a severe disabling condition. Patients with CFS usually trial many different medicines, both conventional and complementary. An overview of the pharmacological treatments used by CFS patients and the available evidence underpinning the use of these treatments would be of great value to both patients and their healthcare providers.

METHODS: Ninety-four CFS patients recruited into an Australian study investigating immunological biomarkers filled out a questionnaire assessing the medicines they were taking. Evidence from randomised clinical trials was sought in biomedical databases.

RESULTS: The 94 CFS patients used 474 different medicines and supplements. The most commonly used medicines were antidepressants, analgesics, sedatives, and B vitamins. We identified 20 randomised controlled trials studying these medicines in CFS patients.

DISCUSSION: While conventional and complementary medicines are widely used by CFS patients, the evidence for effectiveness in CFS is very limited.

Source: Kreijkamp-Kaspers S, Brenu EW, Marshall S, Staines D, Van Driel ML. Treating chronic fatigue syndrome – a study into the scientific evidence for pharmacological treatments. Aust Fam Physician. 2011 Nov;40(11):907-12. http://www.racgp.org.au/download/documents/AFP/2011/November/201111kkaspers.pdf (Full article)

Serotonergic descending inhibition in chronic pain: design, preliminary results and early cessation of a randomized controlled trial

Abstract:

AIM: We examined whether activation of serotonergic descending pathways improves pain inhibition during exercise in patients with chronic fatigue syndrome (CFS) and comorbid fibromyalgia (FM) in comparison with rheumatoid arthritis (RA) and sedentary, healthy controls in a double-blind randomized controlled trial with cross-over design.

PATIENTS AND METHODS: Three female CFS/FM patients, one female RA patient and two healthy women were randomly allocated to the experimental group (2 ml of citalopram intravenously) or the placebo group (2 ml of 0.9% NaCl intravenously). Participants performed a submaximal exercise protocol, preceded and followed by an assessment of endogenous pain inhibition. Seven days later, groups were crossed over.

RESULTS: Significant side-effects were observed in all, but one participant immediately after intravenous administration of citalopram. One CFS/FM patient withdrew because of severe post-exertional malaise.

CONCLUSION: It was decided that proceeding with the study would be unethical. No conclusion could be made regarding pain inhibition during exercise in CFS/FM compared to RA and controls.

Source: Meeus M, Ickmans K, De Clerck LS, Moorkens G, Hans G, Grosemans S, Nijs J. Serotonergic descending inhibition in chronic pain: design, preliminary results and early cessation of a randomized controlled trial. In Vivo. 2011 Nov-Dec;25(6):1019-25. https://www.ncbi.nlm.nih.gov/pubmed/22021700

The effect of homework compliance on treatment outcomes for participants with myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

PURPOSE: This study examined the relationship between level of treatment engagement through completion of homework on treatment outcomes within nonpharmacological interventions for participants with ME/CFS.

METHOD: A sample of 82 participants with ME/CFS was randomly assigned to one of four nonpharmacological interventions. Each intervention involved 13 sessions over the course of 6 months. Change scores were computed for self-report measures taken at baseline and 12-month follow-up. Homework compliance was calculated as the percentage of completed assignments across the total number of sessions and grouped into three categories: minimum (0-25%), moderate (25.1-75%), or maximum (75.1-100%).

RESULTS: Findings revealed that after controlling for treatment condition, those who completed a maximum amount of homework had greater improvement on a number of self-report outcome measures involving role, social, and mental health functioning. There were no differential improvements in physical and fatigue functioning based on level of homework compliance.

IMPLICATIONS: Findings from this study suggest homework compliance can have a positive influence on some aspects of physical, social, and mental health functioning in participants with ME/CFS. It should be emphasized that these interventions do not cure this illness. The lack of significant changes in physical functioning and fatigue levels suggests a need for more multidisciplinary treatment approaches that can elicit improvement in these areas.

Source: Hlavaty LE, Brown MM, Jason LA. The effect of homework compliance on treatment outcomes for participants with myalgic encephalomyelitis/chronic fatigue syndrome. Rehabil Psychol. 2011 Aug;56(3):212-8. doi: 10.1037/a0024118. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3166212/ (Full article)

Chronic fatigue syndrome in the media: a content analysis of newspaper articles

Abstract:

OBJECTIVES: Although cognitive behavioural therapy and graded exercise treatment are recognized evidence-based treatments for chronic fatigue syndrome/myalgic encephalomyelitis (ME), their use is still considered controversial by some patient groups. This debate has been reflected in the media, where many patients gather health information. The aim of this study was to examine how treatment for chronic fatigue syndrome/ME is described in the newspaper media.

DESIGN: Content analysis of newspaper articles.

SETTING: The digitalized media archive Atekst was used to identify Norwegian newspaper articles where chronic fatigue syndrome/ME was mentioned.

PARTICIPANTS: Norwegian newspaper articles published over a 20-month period, from 1 January 2008 to 31 August 2009.

MAIN OUTCOME MEASURES: Statements regarding efficiency of various types of treatment for chronic fatigue syndrome/ME and the related source of the treatment advice. Statements were categorized as being either positive or negative towards evidence-based or alternative treatment.

RESULTS: One hundred and twenty-two statements regarding treatment of chronic fatigue syndrome/ME were identified among 123 newspaper articles. The most frequent statements were positive statements towards alternative treatment Lightning Process (26.2%), negative statements towards evidence-based treatments (22.1%), and positive statements towards other alternative treatment interventions (22.1%). Only 14.8% of the statements were positive towards evidence-based treatment. Case-subjects were the most frequently cited sources, accounting for 35.2% of the statements, followed by physicians and the Norwegian ME association.

CONCLUSIONS: Statements regarding treatment for chronic fatigue syndrome/ME in newspapers are mainly pro-alternative treatment and against evidence-based treatment. The media has great potential to influence individual choices. The unbalanced reporting of treatment options for chronic fatigue syndrome/ME in the media is potentially harmful.

Source: Knudsen AK, Omenås AN, Harvey SB, Løvvik CM, Lervik LV, Mykletun A. Chronic fatigue syndrome in the media: a content analysis of newspaper articles. JRSM Short Rep. 2011 May;2(5):42. doi: 10.1258/shorts.2011.011016. Epub 2011 May 25. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3105457/ (Full article)