[1]: 29 Pacing, or regulating one's activities to avoid triggering worse symptoms, is the most common management strategy for post-exertional malaise.
Pacing encourages behavioral change, but unlike cognitive behavioural therapy, acknowledge the typical patient fluctuations in symptom severity and experience delayed exercise recovery.
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.
[11] In 2019, a large UK found that pacing led to greater improvements in patients' physical health, although a minority did report becoming worse.
[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.
[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.
[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.
[12] Graded exercise therapy (GET) is a programme of physical activity that starts very slowly and gradually increases over time in fixed increments.
[1]: 33, 93 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.
"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.
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".
[39] 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.
[40] 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.
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.
[53] 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.
[51] 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.
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.
[53] In 2008 a randomised double-blind placebo-controlled six-month trial on 96 aged subjects with CFS symptoms administering acetyl L-carnitine was reported.
[70] 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.
[71] 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.
[73] 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.