Use of lisdexamfetamine dimesylate in treatment of executive functioning deficits and chronic fatigue syndrome: a double blind, placebo-controlled study

Abstract:

The purpose of this study was to assess the efficacy of lisdexamfetamine dimesylate (LDX) for the treatment of executive functioning deficits in adults (ages 18-60) with chronic fatigue syndrome (CFS). The study’s primary outcome measure was the Behavior Rating Inventory of Executive Function-Adult (BRIEF-A). Secondary outcome measures were standardized assessments of fatigue, pain and global functioning.

Twenty-six adults who met criteria for CFS and had clinically significant executive functioning deficits were randomly assigned to a flexible morning dose (30, 50, 70 mg/day) of either placebo or LDX for a 6-week trial. The data were analyzed with standard analysis of variance (ANOVA) procedures. Participants in the LDX group showed significantly more positive change in BRIEF-A scores (Mchange=21.38, SD=15.85) than those in the placebo group (Mchange=3.36, SD=7.26).

Participants in the active group also reported significantly less fatigue and generalized pain relative to the placebo group. Although future studies with LDX should examine whether these benefits generalize to larger, more diverse samples of patients, these results suggest that LDX could be a safe and efficacious treatment for the executive functioning deficits often associated with CFS. The possibility that dopaminergic medications could play an important role addressing the symptoms of CFS is also discussed.

Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

 

Source: Young JL. Use of lisdexamfetamine dimesylate in treatment of executive functioning deficits and chronic fatigue syndrome: a double blind, placebo-controlled study. Psychiatry Res. 2013 May 15;207(1-2):127-33. doi: 10.1016/j.psychres.2012.09.007. Epub 2012 Oct 9. https://www.ncbi.nlm.nih.gov/pubmed/23062791

 

Chronic fatigue syndrome: diagnosis and treatment

Abstract:

Chronic fatigue syndrome is characterized by debilitating fatigue that is not relieved with rest and is associated with physical symptoms. The Centers for Disease Control and Prevention criteria for chronic fatigue syndrome include severe fatigue lasting longer than six months, as well as presence of at least four of the following physical symptoms: postexertional malaise; unrefreshing sleep; impaired memory or concentration; muscle pain; polyarthralgia; sore throat; tender lymph nodes; or new headaches. It is a clinical diagnosis that can be made only when other disease processes are excluded. The etiology of chronic fatigue syndrome is unclear, is likely complex, and may involve dysfunction of the immune or adrenal systems, an association with certain genetic markers, or a history of childhood trauma. Persons with chronic fatigue syndrome should be evaluated for concurrent depression, pain, and sleep disturbances. Treatment options include cognitive behavior therapy and graded exercise therapy, both of which have been shown to moderately improve fatigue levels, work and social adjustment, anxiety, and postexertional malaise. No pharmacologic or alternative medicine therapies have been proven effective.

Comment in: Article on CFS does not reflect current best treatment practices. [Am Fam Physician. 2013]

 

Source: Yancey JR, Thomas SM. Chronic fatigue syndrome: diagnosis and treatment. Am Fam Physician. 2012 Oct 15;86(8):741-6. http://www.aafp.org/afp/2012/1015/p741.html (Full article)

 

Immunophenotyping in post-giardiasis functional gastrointestinal disease and chronic fatigue syndrome

Abstract:

BACKGROUND: A Giardia outbreak was associated with development of post-infectious functional gastrointestinal disorders (PI-FGID) and chronic fatigue syndrome (PI-CFS). Markers of immune dysfunction have given conflicting results in CFS and FGID patient populations. The aim of this study was to evaluate a wide selection of markers of immune dysfunction in these two co-occurring post-infectious syndromes.

METHODS: 48 patients, reporting chronic fatigue in a questionnaire study, were clinically evaluated five years after the outbreak and grouped according to Fukuda criteria for CFS (n=19) and idiopathic chronic fatigue (n=5) and Rome II criteria for FGIDs (n=54). 22 Giardia exposed non-fatigued individuals and 10 healthy unexposed individuals were recruited as controls. Peripheral blood lymphocyte subsets were analyzed by flow cytometry.

RESULTS: In peripheral blood we found significantly higher CD8 T-cell levels in PI-FGID, and significantly lower NK-cell levels in PI-CFS patients. Severity of abdominal and fatigue symptoms correlated negatively with NK-cell levels. A tendency towards lower T-cell CD26 expression in FGID was seen.

CONCLUSION: Patients with PI-CFS and/or PI-FGID 5 years after Giardia lamblia infection showed alterations in NK-cell and CD8-cell populations suggesting a possible immunological abnormality in these conditions. We found no significant changes in other markers examined in this well-defined group of PI-CFS and PI-FGID elicited by a gastrointestinal infection. Controlling for co-morbid conditions is important in evaluation of CFS-biomarkers.

 

Source: Hanevik K, Kristoffersen EK, Sørnes S, Mørch K, Næss H, Rivenes AC, Bødtker JE, Hausken T, Langeland N. Immunophenotyping in post-giardiasis functional gastrointestinal disease and chronic fatigue syndrome. BMC Infect Dis. 2012 Oct 14;12:258. doi: 10.1186/1471-2334-12-258. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3553045/ (Full article)

 

Sleep in the chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is a disabling condition characterized by severe fatigue lasting for more than six months and the presence of at least four out of eight minor criteria. Sleep disturbance presenting as unrefreshing or nonrestorative sleep is one of these criteria and is very common in CFS patients. Biologically disturbed sleep is a known cause of fatigue and could play a role in the pathogenesis of CFS. However, the nature of presumed sleep impairment in CFS remains unclear. Whilst complaints of NRS persist over time, there is no demonstrable neurophysiological correlate to substantiate a basic deficit in sleep function in CFS. Polysomnographic findings have not shown to be significantly different between subjects with CFS and normal controls. Discrepancies between subjectively poor and objectively normal sleep suggest a role for psychosocial factors negatively affecting perception of sleep quality. Primary sleep disorders are often detected in patients who otherwise qualify for a CFS diagnosis. These disorders could contribute to the presence of daytime dysfunctioning. There is currently insufficient evidence to indicate that treatment of primary sleep disorders sufficiently improves the fatigue associated with CFS. Therefore, primary sleep disorders may be a comorbid rather than an exclusionary condition with respect to CFS.

Copyright © 2012 Elsevier Ltd. All rights reserved.

 

Source: Mariman AN, Vogelaers DP, Tobback E, Delesie LM, Hanoulle IP, Pevernagie DA. Sleep in the chronic fatigue syndrome. Sleep Med Rev. 2013 Jun;17(3):193-9. doi: 10.1016/j.smrv.2012.06.003. Epub 2012 Oct 6. https://www.ncbi.nlm.nih.gov/pubmed/23046847

 

A Brief Historic Overview of Clinical Disorders Associated with Tryptophan: The Relevance to Chronic Fatigue Syndrome (CFS) and Fibromyalgia (FM)

Abstract:

Last century there was a short burst of interest in the tryptophan related disorders of pellagra and related abnormalities that are usually presented in infancy.1,2 Nutritional physiologists recognized that a severe human dietary deficiency of either tryptophan or the B group vitamins could result in central nervous system (CNS) sequelae such as ataxia, cognitive dysfunction and dysphoria, accompanied by skin hyperpigmentation.3,4 The current paper will focus on the emerging role of tryptophan in chronic fatigue syndrome (CFS) and fibromyalgia (FM).

 

Source: Blankfield A. A Brief Historic Overview of Clinical Disorders Associated with Tryptophan: The Relevance to Chronic Fatigue Syndrome (CFS) and Fibromyalgia (FM). Int J Tryptophan Res. 2012;5:27-32. doi: 10.4137/IJTR.S10085. Epub 2012 Sep 17. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3460668/ (Full article)

 

Predictors of Fatigue among Patients with Chronic Fatigue Syndrome

Abstract:

Activity logs involve patients writing down their activities over one or more days. Several studies have found these data collection instruments to accurately describe activities of patients with chronic fatigue syndrome (CFS). The purpose of this study was to utilize the repeated measures available on the ACTRE to evaluate predictors of fatigue at a given timepoint.

A random intercept model was tested with the following variables predicting current fatigue: past fatigue (30 mins. prior), current category of activity (e.g., resting, work, recreation, etc.), past category of activity (30 mins. prior), the interaction of past fatigue and past activity, and TH2/TH1 immune shift. These findings and others suggest that activity logs can provide investigators and clinicians with valuable sources of data for understanding patterns of behavior and activity among patients with CFS.

 

Source: Jason LA, Brown M, Evans M, Brown A. Predictors of Fatigue among Patients with Chronic Fatigue Syndrome. J Hum Behav Soc Environ. 2012 Oct 1;22(7):822-833. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3955704/ (Full article)

 

Developing resources to support the diagnosis and management of Chronic Fatigue Syndrome/Myalgic Encephalitis (CFS/ME) in primary care: a qualitative study

Abstract:

BACKGROUND: NICE guidelines emphasise the need for a confident, early diagnosis of Chronic Fatigue Syndrome/ Myalgic Encephalitis (CFS/ME) in Primary Care with management tailored to the needs of the patient. Research suggests that GPs are reluctant to make the diagnosis and resources for management are currently inadequate. This study aimed to develop resources for practitioners and patients to support the diagnosis and management of CFS/ME in primary care.

METHODS: Semi structured interviews were conducted with patients, carers, GPs, practice nurses and CFS/ME specialists in North West England. All interviews were audio recorded, transcribed and analysed qualitatively using open explorative thematic coding. Two patient involvement groups were consulted at each stage of the development of resources to ensure that the resources reflect everyday issues faced by people living with CFS/ME.

RESULTS: Patients and carers stressed the importance of recognising CFS/ME as a legitimate condition, and the need to be believed by health care professionals. GPs and practice nurses stated that they do not always have the knowledge or skills to diagnose and manage the condition. They expressed a preference for an online training package. For patients, information on getting the most out of a consultation and the role of carers was thought to be important. Patients did not want to be overloaded with information at diagnosis, and suggested information should be given in steps. A DVD was suggested, to enable information sharing with carers and family, and also for those whose symptoms act as a barrier to reading.

CONCLUSION: Rather than use a top-down approach to the development of training for health care practitioners and information for patients and carers, we have used data from key stakeholders to develop a patient DVD, patient leaflets to guide symptom management and a modular e-learning resource which should equip GPs to diagnose and manage CFS/ME effectively, meet NICE guidelines and give patients acceptable, evidence-based information.

 

Source: Hannon K, Peters S, Fisher L, Riste L, Wearden A, Lovell K, Turner P, Leech Y, Chew-Graham C. Developing resources to support the diagnosis and management of Chronic Fatigue Syndrome/Myalgic Encephalitis (CFS/ME) in primary care: a qualitative study. BMC Fam Pract. 2012 Sep 21;13:93. doi: 10.1186/1471-2296-13-93. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3573921/ (Full article)

 

Pain in patients with chronic fatigue syndrome: time for specific pain treatment?

Abstract:

BACKGROUND: Besides chronic fatigue, patients with chronic fatigue syndrome (CFS) have debilitating widespread pain. Yet pain from CFS is often ignored by clinicians and researchers.

OBJECTIVES: To examine whether pain is a unique feature of CFS, or does it share the same underlying mechanisms as other CFS symptoms? Second, it is examined whether effective treatments for pain from CFS are currently available.

STUDY DESIGN: Narrative review covering the scientific literature up through December 2011.

SETTING: Several universities.

RESULTS: From the available literature, it is concluded that musculoskeletal factors are unlikely to account for pain from CFS. Pain seems to be one out of many symptoms related to central sensitization from CFS. This idea is supported by the findings of generalized hyperalgesia (including widespread increased responsiveness to painful stimuli) and dysfunctional endogenous analgesia in response to noxious thermal stimuli. Pain catastrophizing and depression partly account for pain from CFS. Pain increases during exercise is probably due to the lack of endogenous analgesia and activation of several genes in response to exercise in CFS. There is currently no evidence in support for the efficacy of complementary medicine in the treatment of pain from CFS. Intensive education about the biology of pain from CFS (within the framework of central sensitization) has positive short-term effects for patients with CFS, and fatigue-targeting cognitive behavioral therapy appears to be effective for pain from CFS as well.

LIMITATIONS: The role of the deficient hypothalamus-pituitary-adrenal axis in relation to pain from CFS, as well as the interactions with immune (dys)functioning require further study.

CONCLUSION: Recent research has increased our understanding of pain from CFS, including its treatment. It is advocated to optimize current CFS treatment protocols by targeting the underlying mechanism for those patients having severe pain.

 

Source: Nijs J, Crombez G, Meeus M, Knoop H, Damme SV, Cauwenbergh V, Bleijenberg G. Pain in patients with chronic fatigue syndrome: time for specific pain treatment? Pain Physician. 2012 Sep-Oct;15(5):E677-86. http://www.painphysicianjournal.com/linkout?issn=1533-3159&vol=15&page=E677 (Full article)

 

A multicenter blinded analysis indicates no association between chronic fatigue syndrome/myalgic encephalomyelitis and either xenotropic murine leukemia virus-related virus or polytropic murine leukemia virus

Abstract:

The disabling disorder known as chronic fatigue syndrome or myalgic encephalomyelitis (CFS/ME) has been linked in two independent studies to infection with xenotropic murine leukemia virus-related virus (XMRV) and polytropic murine leukemia virus (pMLV). Although the associations were not confirmed in subsequent studies by other investigators, patients continue to question the consensus of the scientific community in rejecting the validity of the association. Here we report blinded analysis of peripheral blood from a rigorously characterized, geographically diverse population of 147 patients with CFS/ME and 146 healthy subjects by the investigators describing the original association. This analysis reveals no evidence of either XMRV or pMLV infection. I

MPORTANCE Chronic fatigue syndrome/myalgic encephalomyelitis has an estimated prevalence of 42/10,000 in the United States, with annual direct medical costs of $7 billion. Here, the original investigators who found XMRV and pMLV (polytropic murine leukemia virus) in blood of subjects with this disorder report that this association is not confirmed in a blinded analysis of samples from rigorously characterized subjects. The increasing frequency with which molecular methods are used for pathogen discovery poses new challenges to public health and support of science. It is imperative that strategies be developed to rapidly and coherently address discoveries so that they can be carried forward for translation to clinical medicine or abandoned to focus resource investment more productively. Our study provides a paradigm for pathogen discovery that may be helpful to others working in this field.

 

Source: Alter HJ, Mikovits JA, Switzer WM, Ruscetti FW, Lo SC, Klimas N, Komaroff AL, Montoya JG, Bateman L, Levine S, Peterson D, Levin B, Hanson MR, Genfi A, Bhat M, Zheng H, Wang R, Li B, Hung GC, Lee LL, Sameroff S, Heneine W, Coffin J, Hornig M, Lipkin WI. A multicenter blinded analysis indicates no association between chronic fatigue syndrome/myalgic encephalomyelitis and either xenotropic murine leukemia virus-related virus or polytropic murine leukemia virus. MBio. 2012 Sep 18;3(5). pii: e00266-12. doi: 10.1128/mBio.00266-12. Print 2012. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3448165/ (Full article)

 

Experiences of young people who have undergone the Lightning Process to treat chronic fatigue syndrome/myalgic encephalomyelitis–a qualitative study

Abstract:

OBJECTIVES: Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a serious condition characterized by debilitating but unexplained fatigue. Treatment alternatives are few, and especially so for young people. The aetiology of CFS/ME is still unclear and controversial, but rehabilitative interventions seem so far most promising. The Lightning Process is a 3-day training programme that has recently become available, but no outcome studies have yet been published. It is a non-medical training programme that combines concepts from Neuro-Linguistic Programming, Life Coaching and Osteopathy. The aim of this study was to explore the experiences of young people with CFS/ME after they had undergone the Lightning Process.

DESIGN: Qualitative research study.

METHODS: Semi-structured interviews were conducted with an opportunistic sample recruited through open advertisements of nine young people, aged 14-26, who had undergone the treatment, and three of their parents. Inductive thematic analysis was used to evaluate the content of the interviews.

RESULTS: Mostly positive experiences were reported of the Lightning Process. Two reported dissatisfaction and no improvement, while seven were satisfied and were much improved. Particular helpful aspects were the theoretical rationale, practical exercises, and the technique they learned. Less helpful aspects were the intensity and short duration of the treatment with little follow-up, the secrecy surrounding it, and feelings of being blamed if the treatment did not work.

CONCLUSIONS: As this is the first report of young people’s experiences with the Lightning Process, it will be important to consider the helpful and unhelpful treatment components for future refinement of interventions for CFS/ME.

© 2012 The British Psychological Society.

 

Source: Reme SE, Archer N, Chalder T. Experiences of young people who have undergone the Lightning Process to treat chronic fatigue syndrome/myalgic encephalomyelitis–a qualitative study. Br J Health Psychol. 2013 Sep;18(3):508-25. doi: 10.1111/j.2044-8287.2012.02093.x. Epub 2012 Sep 19. https://www.ncbi.nlm.nih.gov/pubmed/22989369