Management of ME/CFS (myalgic encephalomyelitis/chronic fatigue syndrome) focuses on symptoms management, as no treatments that address the root cause of the illness are available. 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. The prognosis of ME/CFS is poor, with recovery considered "rare".
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). Rintatolimod has been approved for import and use in Argentina.
Pacing 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. 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. A 2008 patient survey by Action for ME found pacing to be the most helpful treatment and a 2009 survey of two Norwegian patient organizations (ME-association and MENiN) had found that 96% evaluated pacing as useful. In 2019, a large UK survey found that pacing led to greater improvements in patients' physical health, although a minority did report becoming worse.
Energy envelope theory Energy envelope theory is a form of pacing that states patients should aim to stay within their "envelope" of available energy, as exceeding this limit can lead to the worsening of symptoms after mental and physical exertion (post-exertional malaise), allowing for "modest" gains in functioning as a result. 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".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. Energy envelope theory was first described in 1999. Several studies have found energy envelope theory to be a helpful management strategy for CFS, noting that it reduces symptoms and may increase functioning. Energy envelope theory does not recommend unilaterally increasing or decreasing activity and is not intended as a therapy or cure for CFS.
Energy Envelope Theory has been promoted by various patient groups.
Pacing with a heart rate monitor 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. Randomized controlled trials of pacing using a heart rate monitor are lacking.
Spoon theory 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. 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. Spoon theory is commonly used by people with CFS.
Cognitive behavioral therapy 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 their energy constraints, 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. The CDC currently suggests supportive counseling may be helpful in coping with the impact of the illness, but does not directly suggest CBT.
NICE state that CBT should not be offered as a cure. 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. 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. In 2016, an ARHQ addendum downgraded the evidence for CBT and stated it should not be used as a primary treatment.
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. 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.
CBT has been criticised by patients' organisations because of negative reports from many of their members which have indicated that CBT can sometimes make people worse, a common result across multiple patient surveys. 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. alternative URL: 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.
Graded exercise therapy
Graded exercise therapy (GET) is a programme of physical activity that starts very slowly and gradually increases over time in fixed increments. Most public health bodies, including the CDC and NICE, consider it ineffective, and its safety is disputed. In particular, NICE removed their recommendation for this treatment in 2021.
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. The studies analyzed employed older definitions of CFS, so the effects on current patient cohorts may be different.
Recovery 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".
Drugs
No pharmacological treatments have been established as a cure for ME/CFS, but various drugs are used to manage the symptoms of ME/CFS.
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.
Rintatolimod Nucleic acid (double-stranded RNA) compounds represent a potential 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.
After being used to successfully treat some patients since the late 1980s, one RCT evaluated rintatolimod and found an overall beneficial effect. 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."
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".
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.
Rintatolimod has been approved for marketing and treatment for persons with ME/CFS in Argentina, and in 2019 the U.S. FDA regulatory requirements were met for exportation of rintatolimod from the United States to Argentina.
Antidepressants