Management of ME/CFS

From Wikipedia, the free encyclopedia
(Redirected from ME/CFS treatment)

Management of ME/CFS (myalgic encephalomyelitis/chronic fatigue syndrome) focusses on symptoms management, as no treatments that address the root cause of the illness are available.[1]: 29  Pacing, or regulating one's activities to avoid triggering worse symptoms, is the most common management strategy for post-exertional malaise. Clinical management varies widely, with many patients receiving combinations of therapies.[2]

There are no Food and Drug Administration-approved medications for ME/CFS, although medications are sometimes used without approval for the illness (off-label). Drugs have been used in experimental studies of the illness that have not been approved for market for any condition in the United States (for example, isoprinosine and rintatolimod).[3] Rintatolimod has been approved for import and use in Argentina.[4][5]

Even when treated, the prognosis of ME/CFS is poor, with recovery considered “rare”.[6][7]

Pacing[edit]

Pacing (activity management) is a management strategy rather than a therapy. Pacing encourages behavioral change, but unlike cognitive behavioural therapy, acknowledge the typical patient fluctuations in symptom severity and experience delayed exercise recovery.[8] Pacing does not require patients to increase their activity levels unless they feel able to do so. Patients are advised to set manageable daily activity/exercise goals and balance their activity and rest to avoid possible over-doing which may worsen their symptoms. A small randomised controlled trial concluded pacing with GET had statistically better results than relaxation/flexibility therapy.[8][9] A 2008 patient survey by Action for ME found pacing to be the most helpful treatment[10] and a 2009 survey of two Norwegian patient organizations (ME-association and MENiN) had found that 96% evaluated pacing as useful.[11] In 2019, a large UK found that pacing led to greater improvements in patients' physical health, although a minority did report becoming worse.[12]

Energy envelope theory[edit]

Energy envelope theory is a form of pacing that states patients should aim to stay within their "envelope" of available energy, and by avoiding exceeding their energy levels the worsening of symptoms after mental and physical exertion (post-exertional malaise) should reduce, allowing for "modest" gains in functioning as a result.[13] Energy envelope theory is considered to be consistent with pacing, and is a management strategy suggested in the 2011 international consensus criteria for ME, which refers to using an "energy bank budget".[14] Energy envelope theory was first described in 1999.[15] Several studies have found energy envelope theory to be a helpful management strategy for CFS, noting that it reduces symptoms and may increase functioning.[16][17][18] Energy envelope theory does not recommend unilaterally increasing or decreasing activity and is not intended as a therapy or cure for CFS.[16]

Energy Envelope Theory has been promoted by various patient groups.[19][20]

Pacing with a heart rate monitor[edit]

Some patient groups recommend pacing using a heart rate monitor to increase awareness of exertion, and to allow patients to stay within their aerobic threshold envelope.[21][22] Randomized controlled trials of pacing using a heart rate monitor are lacking.[citation needed]

Spoon theory[edit]

Spoon theory is a way of understanding activity management in chronic illness and is based on the idea that each patient has a limited number of "spoons", with each spoon representing their available energy.[23] A healthy person has an unlimited amount of available energy each day, but a person with chronic illness has a limited amount and must choose which activities to do.[24] Spoon theory is commonly used by people with CFS.[25]

Cognitive behavioral therapy[edit]

Cognitive behaviour therapy (CBT) can be used to help people cope with their illness, and by teaching individuals to better management of rest and activity within the boundaries of the energy constraints of the disorder, and does not actively attempt to improve the patient's physical or psychological capacity. This type of intervention does not assume the symptoms originate from maladaptive illness beliefs.[26] The CDC currently suggests supportive counseling may be helpful in coping with the impact of the illness, but does not directly suggest CBT.[27]

CBT should not be offered as a cure.[1] According to the cognitive-behavioural model of CFS, it is the patient's interpretation of symptoms that primarily shapes their behaviour and perpetuates the illness, and that changing these can lead to complete recovery.[26] Cognitive behavioral therapy (CBT) based on this model attempts to reverse patients' symptoms by altering their interpretation of their symptoms and/or the behaviours they engage in as a result.[26] In 2016, an ARHQ addendum downgraded the evidence for CBT and stated it should not be used as a primary treatment.[28]

A 2010 meta-analysis of trials that objectively measured physical activity before and after CBT showed that although CBT effectively reduced patients' fatigue questionnaire scores, activity levels were not improved by CBT and changes in physical activity were not related to changes in fatigue questionnaire scores. They conclude that the effect of CBT on fatigue questionnaire scores is not mediated by a change in physical activity.[29] According to the authors of a 2014 systematic review, the lack of changes to objectively measured physical activity contradict the cognitive behavioural model of CFS and suggest that patients still avoided postexertional symptom exacerbations and adapted to the illness rather than recovered from it.[30]

Currently there is no research into the effectiveness of CBT for the severely affected, and these patients may be effectively excluded from trials due to the need to attend a clinic.[31]

CBT has been criticised by patients' organisations because of negative reports from many of their members[32] which have indicated that CBT can sometimes make people worse,[33] a common result across multiple patient surveys.[34] One such survey conducted by Action for ME in 2001 found that out of the 285 participants who reported using CBT, 7% reported it to be helpful, 67% reported no change, and 26% reported that it made their condition worse.[35] A large survey commissioned in the UK by NICE for the guidelines review found that CBT for CFS was not effective for more than half of people with CFS, and patients were more likely to get worse physically than to improve.[12]

Graded exercise therapy[edit]

Main article: Graded exercise therapy

Graded exercise therapy (GET) is a programme of physical activity that starts very slowly and gradually increases over time. Most public health bodies, including the CDC and NICE, consider it ineffective, and its safety is disputed.[36][37][38]

A 2019 Cochrane review of 8 studies concluded that GET probably reduces fatigue but that evidence on long-term effectiveness and potential harms are very limited. Effects obtained with exercises were greater than pacing but similar to those obtained with CBT.[39] The studies analyzed employed older definitions of CFS, so the effects on current patient cohorts may be different. An independent analysis of the same studies reached the opposite conclusion based on the unreliability of subjective outcomes in unblinded trials, lack of objective improvements in physical fitness and employment, and insufficient tracking of adverse events.[40]

Even if graded exercise therapy is considered helpful, it does not cure ME/CFS.[7]

Recovery[edit]

A 2014 systematic review reported that estimates of recovery from CFS ranged between 0 and 66% in intervention studies and from 2.6 to 62% in naturalistic studies. There was a lack of consensus in the literature on how recovery should be defined, with almost all of the 22 included studies measuring recovery differently. Recovery was operationally defined by reference to, either alone or in combination: fatigue or related symptoms; function; premorbid function; and/or brief global assessment (which was the most common outcome measure, but does not provide information on symptoms and function, and does not "provide assurance that patients have substantially recovered rather than simply improved"). Focusing on only fatigue or function may overestimate recovery rates, because patients may show selective rather than overall change. A patient with reduced self-reported fatigue may still experience functional disruptions, pain, sleep disturbances, or malaise. "Recovery" in the reviewed studies was often based on limited assessments, less than a full restoration of health, and self-reports with a general lack of more objective measures. In the absence of definitive measures, recovery criteria should set high but reasonable standards for behavioural recovery which approach restoration of pre-morbid health. When objective measures are used, such as the relatively objective behavioural measure of actigraphy, the results have been contrary to the cognitive behavioural model of CFS which predicts increased physical functioning as a result of intervention, as otherwise 'successful' trials did not find significant changes in physical activity. The authors state "a more modest interpretation of 'recovery' might characterize such outcomes as successful adaptation of illness-related behaviour and attitudes to ongoing but perhaps diminished illness", "improved or recovered patients may have continued to avoid activity levels that provoked debilitating postexertional symptom flare-ups", which "would seem to be more consistent with a hypothesis of successful adaptation rather than recovery". It was concluded that more precise and accurate labels other than "recovery" (e.g. clinically significant improvement) may be more appropriate and informative for the improvements reported in previous research, and in keeping with commonly understood conceptions of recovery from illness, recommended a consistent definition of recovery that "captures a broad-based return to health with assessments of both fatigue and function as well as the patient's perceptions of his/her recovery status" and "the recovery time following physical and mental exertion".[30]

Drugs[edit]

No pharmacological treatments have been established as a cure for ME/CFS, but various drugs are used to manage the symptoms of ME/CFS.[41]

In subsets of patients, various viruses and bacteria have been reported as the causative agents of ME/CFS, although consistent and compelling supportive evidence is still lacking. A number of antiviral and antibacterial treatment studies have been conducted with inconsistent results.[42]

Rintatolimod[edit]

Nucleic acid (double-stranded RNA) compounds represent a potential new class of pharmaceutical products that are designed to act at the molecular level, it is an inducer of interferon and is considered to be antiviral and immunomodulatory.

One RCT evaluated rintatolimod and found an overall beneficial effect.[43] In December 2009 the U.S. Food and Drug Administration (FDA) refused to approve a New Drug Application (NDA) by the developer of the drug (Hemispherx Biopharma) to market and sell Ampligen for treatment of ME/CFS. The FDA concluded that the two RCTs submitted "did not provide credible evidence of efficacy."[44]

Hemispherx Biopharma performed additional analyses on their data and submitted a new NDA to the FDA in 2012. After reviewing the data, the FDA did not approve the application citing "insufficient safety and efficacy data".[45]

Rintatolimod has achieved statistically significant improvements in primary endpoints in Phase II and Phase III double-blind, randomized, placebo-controlled clinical trials with a generally well tolerated safety profile and supported by open-label trials in the United States and Europe.[46]

Rintatolimod has been approved for marketing and treatment for persons with ME/CFS in Argentina,[5] and in 2019 the U.S. FDA regulatory requirements were met for exportation of rintatolimod from the United States to Argentina.[4]

Valacyclovir[edit]

Nucleosidic class drugs such as acyclovir, valacyclovir and ganciclovir are inhibitors of viral replication during DNA (for DNA- and retroviruses) or RNA (for RNA viruses) multiplication.[47]

A small 1988 RCT compared acyclovir against placebo and found that an equal proportion of patients improved from placebo and with active treatment. The authors concluded that the improvement reflected either spontaneous remission or the placebo effect.[48] Three people withdrew from acyclovir treatment due to reversible renal failure.[43]

Antidepressants[edit]

Antidepressants are often prescribed to ME/CFS patients. Their purpose can be to treat secondary depression or mood swings, but low dosage tricyclic antidepressants are sometimes prescribed to improve sleep quality and reduce pain.[49]

The evidence for antidepressants is mixed[50] and their use remains controversial.[51] In a review of pharmacological treatments for ME/CFS, five trials of antidepressants were included but only one of these reported a statistically significant improvement in symptoms and this effect was only observed in patients who received 12 weeks of CBT before starting treatment with mirtazapine.[41]

Stimulants[edit]

Psychostimulants such as amphetamine, methylphenidate, and modafinil have been studied in the treatment of CFS.[52][53]

Hormones[edit]

Treatment with steroids and thyroid hormones,[54] such as hydrocortisone, fludrocortisone, and nasal flunisolide,[55] has been studied.

The evidence for corticosteroids is limited. A 2006 systematic review examined RCTs of steroids, primarily hydrocortisone, which found one with a significant difference between groups for fatigue, but two other RCTs found no benefit for steroid treatment. The study which showed statistical significance was noted as scoring poorly for validity.[56]

During a randomized, double-blind trial conducted between 1992 and 1996, hydrocortisone treatment (at a higher dose of 20–30 mg) was associated with some statistical improvement in symptoms of ME/CFS. However, the authors concluded that the degree of adrenal suppression precludes its practical use for ME/CFS.[57] Additionally, long-term use of these medications carry risks of steroid-induced osteoporosis and muscle atrophy.[58]

Fludrocortisone is commonly used for patients with postural orthostatic tachycardia syndrome (POTS) to treat orthostatic intolerance.[59] Given the high comorbidity rate between ME/CFS and POTS,[60] it’s possible that fludrocortisone could reduce symptoms in these patients. However, there is no research available which examines its effect on comorbid ME/CFS and POTS.

NADH[edit]

There is some evidence that NADH is of benefit for CFS patients, particularly in combination with CoQ10.[61] [62][63][64]

Immunotherapy[edit]

Rituximab[edit]

A potential use for rituximab was identified by two Norwegian doctors who were treating people who had cancer with rituximab; two people also had chronic fatigue syndrome and the CFS improved.[54] As of 2017 this use had been explored in some small clinical trials and was undergoing some larger ones; it was unclear as of 2017 whether there is enough benefit in light of the known adverse effects, for rituximab to be a viable treatment for ME/CFS.[54] Results from the 2-year randomized, placebo-controlled, double-blind, multicenter RituxME trial comparing multiple brands of rituximab infusions with placebo in 151 ME/CFS patients concluded that “B-cell depletion using several infusions of rituximab over 12 months was not associated with clinical improvement in patients with ME/CFS,” and thirty-four patients had serious events. “[65][66]

Staphylococcal toxoid vaccine[edit]

There have been[timeframe?] two RCTs with staphylococcal toxoid vaccine. A small RCT showed considerable benefit[67] and a large follow-up RCT showed overall benefit.[68] However the quality of the follow-up RCT was low[citation needed] and there were relatively high levels of adverse effects, although the increase in adverse effects in the treated patients compared to controls did not reach statistical significance.[68] A 2006 review concluded that there is still insufficient evidence for immunological therapies of this type.[56]

Interferon[edit]

A systematic review found two small RCTs that evaluated interferon.[43] One RCT found an overall beneficial effect and the other showed some positive effects in relation to immunological outcomes only. The quality of both of these studies was considered poor.[43] A 2007 review of research needs for ME/CFS concluded that trials for interferon beta are an important priority.[69]

IgG[edit]

A systematic review found five RCTs to have assessed the effects of immunoglobulin treatment for ME/CFS;[43] of these, two RCTs showed an overall beneficial effect and two RCTs showed some positive results, although in one of the studies this was for physiological effects only. The largest of the RCTs found no effect for the treatment. Another review concluded that "Given the weak evidence of benefit for immunotherapy, the potential harms indicate that it should not be offered as a treatment for CFS."[70]

Alternative medicine[edit]

In the absence of proven treatments, alternative medicine treatments are often tried in CFS. Some of these therapies are ineffective while others have not been studied enough to prove any effect. Many studies of alternative treatments for CFS suffer from a high risk of bias.[71]

Dietary supplements[edit]

A 2008 review found insufficient evidence to recommend dietary supplements as a treatment in ME/CFS.

Carnitine[edit]

L-Carnitine is an amino acid which includes ALC, a group of natural compounds that have an important role in cellular function. It is required for the transport of fatty acids into the mitochondria during the breakdown of lipids (fats) for the generation of metabolic energy including in muscles and in the brain.[72] Two RCTs found benefit from dietary supplementation with L-carnitine or its esters. A 2006 systematic review reported one RCT with overall benefit, although there was no placebo control.[56]

In 2008 a randomised double-blind placebo-controlled six-month trial on 96 aged subjects with CFS symptoms administering acetyl L-carnitine was reported. By the end of the treatment, significant differences between the two groups were found for both physical and mental fatigue and improvements in both the cognitive status and physical functions.[73] A 2002 double‐blind randomized controlled trial with 53 patients found no difference in fatigue severity between groups when given a supplement containing 1200 mg carnitine.[74]

Essential fatty acids[edit]

A randomized controlled trial on patients diagnosed with post viral fatigue syndrome (PVFS) and deficient RBC levels, using essential fatty acids consisting of evening primrose oil containing n-6 GLA together with fishoil concentrate containing n-3 EPA and DHA showed significant overall improvement in symptoms and RBC essential fatty acid levels.[75] However a subsequent RCT trying to replicate this study found no significant differences between the treatment and placebo group after treatment, and no significant differences in pre-treatment red-cell membrane lipids between the two groups.[76] The different results may be explained by the patient selection: the first trial tested people with PVFS, whereas the second used the Oxford criteria for CFS. Also, the first trial used paraffin while the second trial used sunflower oil which is better tolerated and less likely to adversely affect the placebo group.[70]

Magnesium[edit]

Positive results from a trial of magnesium delivered by injection to magnesium-deficient CFS patients were published in 1991,[77] but three subsequent studies did not find magnesium deficiency as a general problem in CFS patients. A 2008 review concluded that there is no good evidence that intramuscular magnesium is of benefit in CFS.[70]

Vitamin B12[edit]

Both oral and injected vitamin B12 have been suggested as treatments for generalized fatigue since the 1950s, however recent studies do not suggest any benefit from it, either for generalized fatigue or CFS specifically. Further research is needed, however, as studies to date have been small and used inconsistent dosing regimens.[78]

Controversy[edit]

PACE trial controversy[edit]

The PACE trial was a large-scale five-year trial funded by the UK government which compared the efficacy and safety of four treatments: specialist medical care (SMC), SMC with CBT, SMC with GET, and SMC with adaptive pacing therapy (APT). The results were published in February 2011 and showed that CBT and GET were, when combined with SMC, each "moderately" effective compared to SMC alone. APT was not found to be effective when added to SMC.[79][80]

CBT was done on the basis of the fear avoidance theory of chronic fatigue syndrome. This theory regards CFS as being reversible and that cognitive responses (fear of engaging in activity) and behavioural responses (avoidance of activity) are linked and interact with physiological processes to perpetuate fatigue. The aim of treatment was to change the behavioural and cognitive factors assumed to be responsible for perpetuation of the participant's symptoms and disability.[80]

Graded exercise therapy (GET) was done on the basis of deconditioning and exercise intolerance theories of chronic fatigue syndrome. These theories assume that CFS is perpetuated by reversible physiological changes of deconditioning and avoidance of activity; these changes result in the deconditioning being maintained and an increased perception of effort during exertion and increased symptoms after unaccustomed activity, leading to further inactivity. The aim of treatment was to help the participant gradually return to appropriate physical activities, reverse the deconditioning, and thereby reduce fatigue and disability.[80]

641 patients meeting the Oxford criteria for CFS were recruited, and were assigned approximately evenly to the four treatment conditions. Two weeks after the commencement of the trial, self-reported fatigue scores were significantly lower and self-rated physical function scores significantly higher for the GET and CBT groups than for the SMC and APT groups. At 52 weeks post-treatment, average scores on a 6-minute walking distance test were significantly higher for the GET group than for the other groups. However, the mean distance walked (334 metres) was still well below the mean for healthy elderly people (631 metres). The CBT group did not perform significantly differently from the SMC and APT groups on this measure.[81] A subsequent paper presented results from a step fitness test, but at 52 weeks, there were no significant differences in performance across groups on this measure.[82]

The trial reported that CBT and GET were "safe". A serious adverse event was defined as either: death, life-threatening, hospitalisation, increased severe disability for at least 4 weeks duration, any episode of deliberate self-harm. Serious adverse reactions to the therapies were recorded in two (1%) of the 159 patients in the APT group, three (2%) of the 161 patients in the CBT group, 2 (1%) of the 160 patients in the GET group and two (1%) of the 160 patients in the SMC group.[citation needed]

A subsequent paper examined the proportion of patients who could be classified as recovered after the trial. A patient was considered recovered if they obtained a specified threshold score on the fatigue and physical function self-report scales, if they rated their health as "much better" or "very much better", and if they also failed to meet the authors' case definition of CFS. According to the primary measures of recovery reported in the paper, 22% recovered after CBT, 22% after GET, but only 8% after APT and 7% after SMC.[83]

A follow-up conducted 2.5 years after the commencement of the trial reported no significant differences between the various treatment groups on the primary self-report measures. That is, the treatment-specific effects evident at 52 weeks were no longer evident at 2.5 years.[84]

The publication of the trial results generated a vigorous response. Letters to the editor by some specialists and patient advocates expressed concern over generalisability of the results and questioned protocol changes during the course of the trial that resulted in some participants meeting criteria for "trial recovery" at baseline.[81][85][86][87][88][89] The authors of the paper responded in a letter which stated that the protocol changes and other decisions were approved by the Trial Steering Committee.[90] Patient groups expressed disappointment over news media interpreting the definition of "recovery to normal by trial criteria" as "cured".[91] Professor Malcolm Hooper submitted complaints to the Medical Research Council and the Lancet [2]. The MRC and the Lancet considered the submissions but rejected them. A Lancet editorial expressed suspicions of an active campaign to discredit the research."[92][93]

Controversy has arisen from the authors' and the Lancet's refusal to share data from the study; according to an article in Slate: "Starting in 2011, patients analyzing the study filed Freedom of Information Act requests to learn what the trial's results would have been under the original protocol. Those were denied along with many other requests about the trial, some on the grounds that the requests were 'vexatious.' The investigators said they considered the requests to be harassment. ... Richard Horton, the editor of the Lancet, defended the trial, calling the critics 'a fairly small, but highly organized, very vocal and very damaging group of individuals who have, I would say, actually hijacked this agenda and distorted the debate so that it actually harms the overwhelming majority of patients.'"[94] In 2016, the PACE trial data were made publicly available after a ruling in the UK.[95]

References[edit]

  1. ^ a b "Recommendations – Myalgic encephalomyelitis (or encephalopathy)/chronic fatigue syndrome: diagnosis and management – Guidance". National Institute for Health and Care Excellence (NICE). 29 October 2021. Archived from the original on 8 February 2024. Retrieved 9 March 2024.
  2. ^ Chou R, McDonagh M, Griffins J, Grusing S (2022). Management of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): An Updated Systematic Evidence Review (PDF). Centers for Disease Control and Prevention. Archived (PDF) from the original on 14 February 2024. Retrieved 30 March 2023.
  3. ^ Smith ME, Haney E, McDonagh M, Pappas M, Daeges M, Wasson N, et al. (June 2015). "Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Systematic Review for a National Institutes of Health Pathways to Prevention Workshop". Annals of Internal Medicine. 162 (12): 841–50. doi:10.7326/M15-0114. PMID 26075755. S2CID 28576363.
  4. ^ a b "Rintatolimod for severe Chronic Fatigue Syndrome". fda.gov. 19 September 2019. Retrieved 2020-05-26.
  5. ^ a b Agrawal, Sudhir; Gait, Michael J., eds. (2019-02-11). Advances in Nucleic Acid Therapeutics. Drug Discovery. RSC Publishing. p. 310. doi:10.1039/9781788015714. ISBN 978-1-78801-209-6. Retrieved 2020-05-26.
  6. ^ Luyten P, Van Houdenhove B, Pae CU, Kempke S, Van Wambeke P (December 2008). "Treatment of chronic fatigue syndrome: findings, principles and strategies". Psychiatry Investigation. 5 (4): 209–12. doi:10.4306/pi.2008.5.4.209. PMC 2796012. PMID 20046339.
  7. ^ a b Van Cauwenbergh D, De Kooning M, Ickmans K, Nijs J (October 2012). "How to exercise people with chronic fatigue syndrome: evidence-based practice guidelines". European Journal of Clinical Investigation. 42 (10): 1136–44. doi:10.1111/j.1365-2362.2012.02701.x. PMID 22725992. S2CID 24546500.
  8. ^ a b Nijs J, Meeus M, De Meirleir K (August 2006). "Chronic musculoskeletal pain in chronic fatigue syndrome: recent developments and therapeutic implications". Manual Therapy. 11 (3): 187–91. doi:10.1016/j.math.2006.03.008. PMID 16781183.
  9. ^ Wallman KE, Morton AR, Goodman C, Grove R, Guilfoyle AM (May 2004). "Randomised controlled trial of graded exercise in chronic fatigue syndrome". The Medical Journal of Australia. 180 (9): 444–48. doi:10.5694/j.1326-5377.2004.tb06019.x. PMID 15115421. S2CID 16924241.
  10. ^ "Survey Summary Report 2008" (PDF). Action for ME. 2008. p. 13. Retrieved 8 March 2010.
  11. ^ Bjørkum T, Wang CE, Waterloo K (June 2009). "[Patients' experience with treatment of chronic fatigue syndrome]". Tidsskrift for den Norske Laegeforening. 129 (12): 1214–16. doi:10.4045/tidsskr.09.35791. PMID 19521443.
  12. ^ a b "Forward-ME and Oxford Brookes University announce results of the patient survey on CBT and GET in ME/CFS". ME Association. 3 April 2019. Retrieved 25 May 2020.
  13. ^ Jason LA, Brown M, Brown A, Evans M, Flores S, Grant-Holler E, Sunnquist M (January 2013). "Energy Conservation/Envelope Theory Interventions to Help Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome". Fatigue. 1 (1–2): 27–42. doi:10.1080/21641846.2012.733602. PMC 3596172. PMID 23504301.
  14. ^ Carruthers BM, van de Sande MI, De Meirleir KL, Klimas NG, Broderick G, Mitchell T, Staines D, Powles ACP, Speight N, Vallings R, Bateman L, Bell DS, Carlo-Stella N, Chia J, Darragh A, Gerken A, Jo D, Lewis D, Light AR, Light K, Marshall-Gradisnik S, McLaren-Howard J, Mena I, Miwa K, Murovska M, Steven S (2012). Myalgic Encephalomyelitis – Adult & Paediatric: International Consensus Primer for Medical Practitioners Authors – International Consensus Panel.
  15. ^ Jason LA, Melrose H, Lerman A, Burroughs V, Lewis K, King CP, Frankenberry EL (January 1999). "Managing chronic fatigue syndrome: overview and case study". AAOHN Journal. 47 (1): 17–21. doi:10.1177/216507999904700104. PMID 10205371.
  16. ^ a b Jason L, Muldowney K, Torres-Harding S (May 2008). "The Energy Envelope Theory and myalgic encephalomyelitis/chronic fatigue syndrome". AAOHN Journal. 56 (5): 189–95. doi:10.3928/08910162-20080501-06. PMID 18578185. S2CID 25558691.
  17. ^ Brown M, Khorana N, Jason LA (March 2011). "The role of changes in activity as a function of perceived available and expended energy in nonpharmacological treatment outcomes for ME/CFS". Journal of Clinical Psychology. 67 (3): 253–60. doi:10.1002/jclp.20744. PMC 3164291. PMID 21254053.
  18. ^ O'connor K, Sunnquist M, Nicholson L, Jason LA, Newton JL, Strand EB (March 2019). "Energy envelope maintenance among patients with myalgic encephalomyelitis and chronic fatigue syndrome: Implications of limited energy reserves". Chronic Illness. 15 (1): 51–60. doi:10.1177/1742395317746470. PMC 5750135. PMID 29231037.
  19. ^ Campbell, B (Winter 2009). "Managing your energy envelope" (PDF). The CFIDS Chronicle: 28–31. Archived from the original (PDF) on 2020-09-27. Retrieved 2020-05-26.
  20. ^ "Pacing - Emerge Australia". Emerge Australia. Retrieved 2020-05-23.[permanent dead link]
  21. ^ Steefel, Lorraine (2011-09-15). What Nurses Know...Chronic Fatigue Syndrome. Demos Medical Publishing. pp. 54–55. ISBN 978-1-61705-028-2.
  22. ^ Campbell, Bruce (14 November 2009). "Pacing by Numbers: using your heart rate to stay inside the energy envelope". ME/CFS South Australia Inc. Retrieved 2020-05-23.
  23. ^ Miserandino, Christine (2003). "The Spoon Theory". But You Don't Look Sick. Archived from the original on 17 November 2019. Retrieved 5 July 2017.
  24. ^ Alhaboby, Zhraa A.; Barnes, James; Evans, Hala; Short, Emma (2018). "Disability and Cyber-Victimization". In Schatz, J.L.; George, Amber E. (eds.). The Image of Disability: Essays on Media Representations. Jefferson, North Carolina: McFarland & Company. pp. 167ff. ISBN 978-1-4766-6945-8.
  25. ^ Hale, Catherine (2018). "Reclaiming 'Chronic Illness" (PDF). Centre for Welfare Reform. p. 28. Retrieved 20 May 2020.
  26. ^ a b c Price JR, Mitchell E, Tidy E, Hunot V (July 2008). "Cognitive behaviour therapy for chronic fatigue syndrome in adults". The Cochrane Database of Systematic Reviews. 2021 (3): CD001027. doi:10.1002/14651858.CD001027.pub2. PMC 7028002. PMID 18646067.Closed access icon
  27. ^ "Treatment of ME/CFS | Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) | CDC". www.cdc.gov. 2019-11-19. Retrieved 2020-05-23.
  28. ^ Smith ME, Nelson HD, Haney E, Pappas M, Daeges M, Wasson N, McDonagh M (December 2014). "July 2016 Addendum". Diagnosis and Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome No. 219 (Evidence Report/Technology Assessment). Agency for Healthcare Research and Quality (US). pp. 1–433. doi:10.23970/AHRQEPCERTA219. PMID 30313001. The results are consistent across trials with improvement in function, fatigue, and global improvement and provided moderate strength of evidence for improved function (4 trials, n=607) and global improvement (3 trials, n=539), low strength of evidence for reduced fatigue (4 trials, n=607) and decreased work impairment (1 trial, n=480), and insufficient evidence for improved quality of life (no trials)
  29. ^ Wiborg JF, Knoop H, Stulemeijer M, Prins JB, Bleijenberg G (August 2010). "How does cognitive behaviour therapy reduce fatigue in patients with chronic fatigue syndrome? The role of physical activity". Psychological Medicine. 40 (8): 1281–87. doi:10.1017/S0033291709992212. hdl:2066/88308. PMID 20047707. S2CID 1706713.
  30. ^ a b Adamowicz JL, Caikauskaite I, Friedberg F (November 2014). "Defining recovery in chronic fatigue syndrome: a critical review". Quality of Life Research. 23 (9): 2407–16. doi:10.1007/s11136-014-0705-9. PMID 24791749. S2CID 13609292.
  31. ^ Chambers, Duncan; Bagnall, Anne-Marie; Hempel, Susanne; Forbes, Carol (2006). "Interventions for the treatment, management and rehabilitation of patients with chronic fatigue syndrome/myalgic encephalomyelitis: an updated systematic review". J. R. Soc. Med. 99 (10): 506–20. doi:10.1177/014107680609901012. PMC 1592057. PMID 17021301.
  32. ^ Clark C, Buchwald D, MacIntyre A, Sharpe M, Wessely S (January 2002). "Chronic fatigue syndrome: a step towards agreement" (PDF). Lancet. 359 (9301): 97–98. doi:10.1016/S0140-6736(02)07336-1. PMID 11809249. S2CID 38526912. Archived from the original (PDF) on 2007-10-12.
  33. ^ White PD, Sharpe MC, Chalder T, DeCesare JC, Walwyn R (March 2007). "Protocol for the PACE trial: a randomised controlled trial of adaptive pacing, cognitive behaviour therapy, and graded exercise, as supplements to standardised specialist medical care versus standardised specialist medical care alone for patients with the chronic fatigue syndrome/myalgic encephalomyelitis or encephalopathy". BMC Neurology. 7: 6. doi:10.1186/1471-2377-7-6. PMC 2147058. PMID 17397525.
  34. ^ Twisk FN, Maes M (August 2009). "A review on cognitive behavorial therapy (CBT) and graded exercise therapy (GET) in myalgic encephalomyelitis (ME) / chronic fatigue syndrome (CFS): CBT/GET is not only ineffective and not evidence-based, but also potentially harmful for many patients with ME/CFS". Neuro Endocrinology Letters. 30 (3): 284–99. PMID 19855350. Archived from the original on 2011-02-24. Retrieved 2010-08-17.
  35. ^ Working Party on CFS/ME (January 2002). "Report of the Working Party on CFS/ME to the Chief Medical Officer for England and Wales". Department of Health. Archived from the original on 2011-03-22. Retrieved 2009-03-18. alternative URL: [1]
  36. ^ "Myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS) - Treatment". nhs.uk. 2017-10-20. Retrieved 2024-03-17.
  37. ^ Bateman, Lucinda; Bested, Alison C.; Bonilla, Hector F.; Chheda, Bela V.; Chu, Lily; Curtin, Jennifer M.; Dempsey, Tania T.; Dimmock, Mary E.; Dowell, Theresa G.; Felsenstein, Donna; Kaufman, David L.; Klimas, Nancy G.; Komaroff, Anthony L.; Lapp, Charles W.; Levine, Susan M. (November 2021). "Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Essentials of Diagnosis and Management". Mayo Clinic Proceedings. 96 (11): 2861–2878. doi:10.1016/j.mayocp.2021.07.004. ISSN 0025-6196. PMID 34454716.
  38. ^ "Diagnosis and Treatment of Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome". effectivehealthcare.ahrq.gov. Retrieved 2024-03-17.
  39. ^ Larun, Lillebeth; Brurberg, Kjetil G.; Odgaard-Jensen, Jan; Price, Jonathan R. (2 October 2019). "Exercise therapy for chronic fatigue syndrome". The Cochrane Database of Systematic Reviews. 10 (3): CD003200. doi:10.1002/14651858.CD003200.pub8. ISSN 1469-493X. PMC 6953363. PMID 31577366.
  40. ^ Vink, Mark; Vink-Niese, Friso (2020-01-01). "Graded exercise therapy does not restore the ability to work in ME/CFS – Rethinking of a Cochrane review". Work. 66 (2): 283–308. doi:10.3233/WOR-203174. ISSN 1051-9815. PMID 32568149.
  41. ^ a b Kreijkamp-Kaspers S, Brenu EW, Marshall S, Staines D, Van Driel ML (November 2011). "Treating chronic fatigue syndrome – a study into the scientific evidence for pharmacological treatments". Australian Family Physician. 40 (11): 907–12. PMID 22059223.
  42. ^ Newberry F, Hsieh SY, Wileman T, Carding SR (March 2018). "Does the microbiome and virome contribute to myalgic encephalomyelitis/chronic fatigue syndrome?". Clinical Science. 132 (5): 523–42. doi:10.1042/CS20171330. PMC 5843715. PMID 29523751.
  43. ^ a b c d e Whiting P, Bagnall AM, Sowden AJ, Cornell JE, Mulrow CD, Ramírez G (September 2001). "Interventions for the treatment and management of chronic fatigue syndrome: a systematic review". JAMA. 286 (11): 1360–68. doi:10.1001/jama.286.11.1360. PMID 11560542.
  44. ^ George J (December 3, 2009). "FDA rejects Hemispherx's chronic fatigue drug Ampligen". Philadelphia Business Journal. Retrieved 2010-02-12.
  45. ^ "FDA Response Letter Regarding Approval of Ampligen for ME/CFS". FDA. Archived from the original on 2017-01-13.
  46. ^ Mitchell WM (June 2016). "Efficacy of rintatolimod in the treatment of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME)". Expert Review of Clinical Pharmacology. 9 (6): 755–70. doi:10.1586/17512433.2016.1172960. PMC 4917909. PMID 27045557.
  47. ^ De Clercq E, Neyts J (2009). "Antiviral Agents Acting as DNA or RNA Chain Terminators". Antiviral Strategies. Handbook of Experimental Pharmacology. Vol. 189. pp. 53–84. doi:10.1007/978-3-540-79086-0_3. ISBN 978-3-540-79085-3. PMID 19048197.
  48. ^ Straus SE, Dale JK, Tobi M, Lawley T, Preble O, Blaese RM, et al. (December 1988). "Acyclovir treatment of the chronic fatigue syndrome. Lack of efficacy in a placebo-controlled trial". The New England Journal of Medicine. 319 (26): 1692–98. doi:10.1056/NEJM198812293192602. PMID 2849717.
  49. ^ Bell, David S. (1994). The Doctor's Guide to Chronic Fatigue Syndrome. Da Capo Press. p. 163. ISBN 978-0-201-40797-6.
  50. ^ Jackson JL, O'Malley PG, Kroenke K (March 2006). "Antidepressants and cognitive-behavioral therapy for symptom syndromes". CNS Spectrums. 11 (3): 212–22. doi:10.1017/S1092852900014383. PMID 16575378. S2CID 46719420.
  51. ^ Pae CU, Marks DM, Patkar AA, Masand PS, Luyten P, Serretti A (July 2009). "Pharmacological treatment of chronic fatigue syndrome: focusing on the role of antidepressants". Expert Opinion on Pharmacotherapy. 10 (10): 1561–70. doi:10.1517/14656560902988510. PMID 19514866. S2CID 20727319.
  52. ^ Van Houdenhove B, Pae CU, Luyten P (February 2010). "Chronic fatigue syndrome: is there a role for non-antidepressant pharmacotherapy?". Expert Opin Pharmacother. 11 (2): 215–23. doi:10.1517/14656560903487744. PMID 20088743. S2CID 34827174.
  53. ^ Valdizán Usón JR, Idiazábal Alecha MA (June 2008). "Diagnostic and treatment challenges of chronic fatigue syndrome: role of immediate-release methylphenidate". Expert Rev Neurother. 8 (6): 917–27. doi:10.1586/14737175.8.6.917. PMID 18505357. S2CID 37482754.
  54. ^ a b c Castro-Marrero J, Sáez-Francàs N, Santillo D, Alegre J (March 2017). "Treatment and management of chronic fatigue syndrome/myalgic encephalomyelitis: all roads lead to Rome". British Journal of Pharmacology. 174 (5): 345–69. doi:10.1111/bph.13702. PMC 5301046. PMID 28052319.
  55. ^ Kakumanu, Sujani S.; Mende, Cathy N.; Lehman, Erik B.; Hughes, Kathleen; Craig, Timothy J. (September 2003). "Effect of topical nasal corticosteroids on patients with chronic fatigue syndrome and rhinitis". The Journal of the American Osteopathic Association. 103 (9): 423–427. ISSN 0098-6151. PMID 14527077.
  56. ^ a b c Chambers D, Bagnall AM, Hempel S, Forbes C (October 2006). "Interventions for the treatment, management and rehabilitation of patients with chronic fatigue syndrome/myalgic encephalomyelitis: an updated systematic review". Journal of the Royal Society of Medicine. 99 (10): 506–20. doi:10.1177/014107680609901012. PMC 1592057. PMID 17021301.
  57. ^ McKenzie R, O'Fallon A, Dale J, Demitrack M, Sharma G, Deloria M, et al. (1998). "Low-dose hydrocortisone for treatment of chronic fatigue syndrome: a randomized controlled trial". JAMA. 280 (12): 1061–66. doi:10.1001/jama.280.12.1061. PMID 9757853.
  58. ^ Klein, Gordon L. (2015-09-01). "The effect of glucocorticoids on bone and muscle". Osteoporosis and Sarcopenia. 1 (1): 39–45. doi:10.1016/j.afos.2015.07.008. ISSN 2405-5255. PMC 4635469. PMID 26557727.
  59. ^ Freitas, J.; Santos, R.; Azevedo, E.; Costa, O.; Carvalho, M.; de Freitas, A. F. (October 2000). "Clinical improvement in patients with orthostatic intolerance after treatment with bisoprolol and fludrocortisone". Clinical Autonomic Research. 10 (5): 293–299. doi:10.1007/BF02281112. ISSN 0959-9851. PMID 11198485. S2CID 20843222.
  60. ^ Hoad, A.; Spickett, G.; Elliott, J.; Newton, J. (December 2008). "Postural orthostatic tachycardia syndrome is an under-recognized condition in chronic fatigue syndrome". QJM: Monthly Journal of the Association of Physicians. 101 (12): 961–965. doi:10.1093/qjmed/hcn123. ISSN 1460-2393. PMID 18805903.
  61. ^ Toogood PL, Clauw DJ, Phadke S, Hoffman D (March 2021). "Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): Where will the drugs come from?". Pharmacological Research. 165: 105465. doi:10.1016/j.phrs.2021.105465. PMID 33529750. S2CID 231787959.
  62. ^ Castro-Marrero J, Sáez-Francàs N, Santillo D, Alegre J (March 2017). "Treatment and management of chronic fatigue syndrome/myalgic encephalomyelitis: all roads lead to Rome". British Journal of Pharmacology. 174 (5): 345–369. doi:10.1111/bph.13702. PMC 5301046. PMID 28052319.
  63. ^ Castro-Marrero, Jesús; et al. (2015). "Does oral coenzyme Q10 plus NADH supplementation improve fatigue and biochemical parameters in chronic fatigue syndrome?". Antioxid Redox Signal. 22 (8): 679–685. doi:10.1089/ars.2014.6181. PMC 4346380. PMID 25386668.
  64. ^ Castro-Marrera, Jesus; et al. (2021). "Effect of Dietary Coenzyme Q10 Plus NADH Supplementation on Fatigue Perception and Health-Related Quality of Life in Individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Prospective, Randomized, Double-Blind, Placebo-Controlled Trial". Nutrients. 13 (8): 2658. doi:10.3390/nu13082658. PMC 8399248. PMID 34444817.
  65. ^ "Rituximab Fails to Improve Symptoms in ME/CFS".
  66. ^ Fluge Ø, Rekeland IG, Lien K, Thürmer H, Borchgrevink PC, Schäfer C, et al. (May 2019). "B-Lymphocyte Depletion in Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial". Annals of Internal Medicine. 170 (9): 585–93. doi:10.7326/M18-1451. PMID 30934066. S2CID 91186383.
  67. ^ Andersson M, Bagby JR, Dyrehag L, Gottfries C (1998). "Effects of staphylococcus toxoid vaccine on pain and fatigue in patients with fibromyalgia/chronic fatigue syndrome". European Journal of Pain. 2 (2): 133–42. doi:10.1016/S1090-3801(98)90006-4. PMID 10700309. S2CID 46726070.
  68. ^ a b Zachrisson O, Regland B, Jahreskog M, Jonsson M, Kron M, Gottfries CG (2002). "Treatment with staphylococcus toxoid in fibromyalgia/chronic fatigue syndrome--a randomised controlled trial". European Journal of Pain. 6 (6): 455–66. doi:10.1016/s1090-3801(02)00044-7. PMID 12413434. S2CID 21526347.
  69. ^ Kerr JR, Christian P, Hodgetts A, Langford PR, Devanur LD, Petty R, et al. (February 2007). "Current research priorities in chronic fatigue syndrome/myalgic encephalomyelitis: disease mechanisms, a diagnostic test and specific treatments". Journal of Clinical Pathology. 60 (2): 113–16. doi:10.1136/jcp.2006.042374. PMC 1860619. PMID 16935968.
  70. ^ a b c Reid S, Chalder T, Cleare A, Hotopf M, Wessely S (26 May 2011). "Chronic fatigue syndrome". BMJ Clinical Evidence. 2011. BMJ Publishing Group. PMC 3275316. PMID 21615974.Closed access icon
  71. ^ Alraek, Terje; Lee, Myeong Soo; Choi, Tae-Young; Cao, Huijuan; Liu, Jianping (2011-10-07). "Complementary and alternative medicine for patients with chronic fatigue syndrome: A systematic review". BMC Complementary and Alternative Medicine. 11 (1): 87. doi:10.1186/1472-6882-11-87. ISSN 1472-6882. PMC 3201900. PMID 21982120.
  72. ^ Inazu M, Matsumiya T (June 2008). "[Physiological functions of carnitine and carnitine transporters in the central nervous system]". Nihon Shinkei Seishin Yakurigaku Zasshi = Japanese Journal of Psychopharmacology (in Japanese). 28 (3): 113–20. PMID 18646596.
  73. ^ Malaguarnera M, Gargante MP, Cristaldi E, Colonna V, Messano M, Koverech A, et al. (2008). "Acetyl L-carnitine (ALC) treatment in elderly patients with fatigue". Archives of Gerontology and Geriatrics. 46 (2): 181–90. doi:10.1016/j.archger.2007.03.012. PMID 17658628.
  74. ^ Brouwers FM, Van Der Werf S, Bleijenberg G, Van Der Zee L, Van Der Meer JW (October 2002). "The effect of a polynutrient supplement on fatigue and physical activity of patients with chronic fatigue syndrome: a double-blind randomized controlled trial". QJM. 95 (10): 677–83. doi:10.1093/qjmed/95.10.677. PMID 12324640.
  75. ^ Behan PO, Behan WM, Horrobin D (September 1990). "Effect of high doses of essential fatty acids on the postviral fatigue syndrome". Acta Neurologica Scandinavica. 82 (3): 209–16. doi:10.1111/j.1600-0404.1990.tb04490.x. PMID 2270749. S2CID 31690317.
  76. ^ Warren G, McKendrick M, Peet M (February 1999). "The role of essential fatty acids in chronic fatigue syndrome. A case-controlled study of red-cell membrane essential fatty acids (EFA) and a placebo-controlled treatment study with high dose of EFA". Acta Neurologica Scandinavica. 99 (2): 112–16. doi:10.1111/j.1600-0404.1999.tb00667.x. PMID 10071170. S2CID 23870977.
  77. ^ Cox IM, Campbell MJ, Dowson D (March 1991). "Red blood cell magnesium and chronic fatigue syndrome". Lancet. 337 (8744): 757–60. doi:10.1016/0140-6736(91)91371-Z. PMID 1672392. S2CID 22160099.
  78. ^ "Does Vitamin B12 Help Relieve Fatigue?". Medscape. Retrieved 2010-12-10.
  79. ^ "PACE Trial – FAQ". Archived from the original on 3 February 2010. Retrieved 9 May 2014.
  80. ^ a b c White PD, Goldsmith KA, Johnson AL, Potts L, Walwyn R, DeCesare JC, et al. (March 2011). "Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial". Lancet. 377 (9768): 823–36. doi:10.1016/S0140-6736(11)60096-2. PMC 3065633. PMID 21334061.
  81. ^ a b Kewley AJ (May 2011). "The PACE trial in chronic fatigue syndrome". Lancet. 377 (9780): 1832, author reply 1834–35. doi:10.1016/S0140-6736(11)60681-8. PMID 21592552.
  82. ^ Chalder T, Goldsmith KA, White PD, Sharpe M, Pickles AR (February 2015). "Rehabilitative therapies for chronic fatigue syndrome: a secondary mediation analysis of the PACE trial". The Lancet. Psychiatry. 2 (2): 141–52. doi:10.1016/S2215-0366(14)00069-8. PMID 26359750.
  83. ^ White PD, Goldsmith K, Johnson AL, Chalder T, Sharpe M (October 2013). "Recovery from chronic fatigue syndrome after treatments given in the PACE trial". Psychological Medicine. 43 (10): 2227–35. doi:10.1017/S0033291713000020. PMC 3776285. PMID 23363640.
  84. ^ Sharpe M, Goldsmith KA, Johnson AL, Chalder T, Walker J, White PD (December 2015). "Rehabilitative treatments for chronic fatigue syndrome: long-term follow-up from the PACE trial" (PDF). The Lancet. Psychiatry. 2 (12): 1067–74. doi:10.1016/S2215-0366(15)00317-X. PMID 26521770.
  85. ^ Mitchell JT (May 2011). "The PACE trial in chronic fatigue syndrome". Lancet. 377 (9780): 1831, author reply 1834–35. doi:10.1016/S0140-6736(11)60683-1. PMID 21592555.
  86. ^ Feehan SM (May 2011). "The PACE trial in chronic fatigue syndrome". Lancet. 377 (9780): 1831–32. doi:10.1016/S0140-6736(11)60688-0. PMID 21592556.
  87. ^ Stouten B, Goudsmit EM, Riley N (May 2011). "The PACE trial in chronic fatigue syndrome". Lancet. 377 (9780): 1832–33, author reply 1834–35. doi:10.1016/S0140-6736(11)60685-5. PMID 21592558.
  88. ^ Kindlon T (May 2011). "The PACE trial in chronic fatigue syndrome". Lancet. 377 (9780): 1833, author reply 1834–35. doi:10.1016/S0140-6736(11)60684-3. PMID 21592560.
  89. ^ Shinohara M (May 2011). "The PACE trial in chronic fatigue syndrome". Lancet. 377 (9780): 1833–34, author reply 1834–35. doi:10.1016/S0140-6736(11)60686-7. PMID 21592561. S2CID 46341672.
  90. ^ White, P; Goldsmith, K; Johnson, A; et al. (May 2011). "The PACE trial in chronic fatigue syndrome – Author's reply". The Lancet. 377 (9780): 1834–35. doi:10.1016/S0140-6736(11)60651-X. S2CID 54402456.
  91. ^ Shepherd C (August 2013). "Letter to the editor: comments on 'Recovery from chronic fatigue syndrome after treatments given in the PACE trial'". Psychological Medicine. 43 (8): 1790–91. doi:10.1017/S003329171300130X. PMID 23866116.
  92. ^ "Patients' power and PACE". Editorial. Lancet. 377 (9780): 1808. May 2011. doi:10.1016/S0140-6736(11)60696-X. PMID 21592553. S2CID 32809857.
  93. ^ Hawkes N (June 2011). "Dangers of research into chronic fatigue syndrome". Comment. BMJ. 342: d3780. doi:10.1136/bmj.d3780. PMID 21697226. S2CID 27301336.
  94. ^ Julie Rehmeyer (13 November 2015). "Hope for Chronic Fatigue Syndrome: The debate over this mysterious disease is suddenly shifting". Slate.
  95. ^ Wilshire, Carolyn; Kindlon, Tom; Matthees, Alem; McGrath, Simon (2017-01-02). "Can patients with chronic fatigue syndrome really recover after graded exercise or cognitive behavioural therapy? A critical commentary and preliminary re-analysis of the PACE trial". Fatigue: Biomedicine, Health & Behavior. 5 (1): 43–56. doi:10.1080/21641846.2017.1259724. ISSN 2164-1846.

External links[edit]

Retrieved from "https://en.wikipedia.org/w/index.php?title=Management_of_ME/CFS&oldid=1219622979"