36 HOW TO TREAT: MYALGIC ENCEPHALOMYELITIS / CHRONIC FATIGUE SYNDROME
36 HOW TO TREAT: MYALGIC ENCEPHALOMYELITIS / CHRONIC FATIGUE SYNDROME
18 JULY 2025 ausdoc. com. au
Importantly, there is no validated international diagnostic / screening test for ME / CFS. Previous reports suggest the use of lymphocyte profiles as a potential biomarker for ME / CFS. However, recent research has focused on cellular markers for the development of a diagnostic / screening high throughput test. These include lymphoblast mitochondrial respiratory function, target of rapamycin complex 1, calcium mobilisation and impaired transient receptor potential melastatin 3
3, 18, 44 channel function( see figure 4).
MANAGEMENT
THERE are no universal evidence-based treatments for ME / CFS. The primary goals of treatment are to manage symptoms to improve functional capacity( see table 3). The management of ME / CFS may incorporate a supportive healthcare advisory team of occupational therapists, physiotherapists, nutritionists and other appropriate health practitioners. This multidisciplinary care aims to advise on self-management strategies, rehabilitative support, co-ordinated primary care and pharmacological interventions.
It is essential to be aware of accommodations that may be necessary for ongoing care of an individual with ME / CFS, including online or phone consultations, home visits or managing the environment to limit strong scents, lights and noises. Many individuals with ME / CFS report neurosensory manifestations, such as sensitivities to light, noise and odours. It is also advisable to remove perfume and chemicals from their environment and to recommend the use of eye masks or ear plugs.
Self-management strategies include the concept of an energy envelope and the practice of pacing. An energy envelope is the energy a patient living with ME / CFS perceives they have available to ensure a balance between energy expenditure and energy replenishment. Pacing is considered one of the most beneficial treatments for ME / CFS, according to NICE, the CDC and the National Institutes of Health. This strategy aims to avoid the onset of post-exertional symptoms or exacerbation of symptoms following cognitive / mental or physical exertion, combined with managing the individual’ s energy envelope and determining exertional tolerance in an effort to reduce the burden of symptoms.
Graded exercise therapy( GET) is not recommended for the treatment of ME / CFS because of the potential for harm. Evidence to support the use of GET is unsubstantiated as a result of inappropriate control groups, including patients who did not fulfil criteria, as well as selective reporting. 45 Research into physical exercise for ME / CFS has shown it causes the onset of PEM and does not improve employment outcomes in those with ME / CFS because of a lack of recovery from GET and biased data. 46 There is widespread concern that exercise programs, even graded, may result in deterioration of the patient’ s condition given the underlying pathology of disease and post-exertional triggers.
Since around 25 % of patients with ME / CFS are considered severe, mobility aids are essential to improve quality of life and assist individuals in maintaining the limits of their energy
Figure 3. The image shows higher T1 / T2-weighted signal intensity across 17 ME / CFS patients compared with 27 healthy controls. A sagittal slice shows higher signal intensity in the pons region( blue arrow). A coronal slice shows higher signal intensity in the amygdala region( blue arrow), and an axial slice shows higher signal intensity in the corpus callosum region( blue arrow) and also demonstrates overall higher signal intensity in the white matter regions.
Table 2. Summary of potential pathomechanisms reported in ME / CFS research
Mechanism Research findings ME / CFS Immune dysregulation
Neurological disturbances
Gastrointestinal disturbances
Metabolic and mitochondrial dysfunction
envelope. These aids may include disability parking permits, wheelchairs or motorised scooters and appropriate home modifications as guided by an occupational therapist.
There is much discussion regarding the use of CBT or mindfulness as a treatment or cure for ME / CFS. It is important that the introduction of CBT does not reflect the belief that ME / CFS is of psychological origin. Instead, this approach aims to improve coping strategies, for both the patient and their family, following the diagnosis of a chronic disease. Caution is advised as the use of CBT is considered controversial and there is limited research on the potential long-term benefits. Chronic conditions do pose a significant
Innate immune exhaustion Cytokine storm Autoantibodies
Neuroinflammation Reduced cerebral blood flow Impaired functional connectivity Brain metabolites Changes in brain region volumes
Dysbiosis Gut – immune – brain axis
Mitochondrial dysfunction Mitochondrial metabolite abnormalities
X denotes research findings present in ME / CFS compared with healthy populations
X X X
X X X X X
X X
X X
burden to psychological health. Protocols for CBT or mindfulness are not standardised for the treatment of ME / CFS, fibromyalgia or long COVID. 5 CBT and mindfulness are most widely studied as psychological interventions for managing pain. 47
Further, there are numerous management strategies to address the multisystemic symptoms of ME / CFS. These symptoms include irritable bowel syndrome, sleep disturbances, pain and orthostatic intolerance. 5 Food avoidance practices and dietary modifications are commonly undertaken to avoid the onset or exacerbation of symptoms. While ME / CFS patients self-report improvements in symptom severity or occurrence, there is limited research to
Figure permissions provided by Dr Kiran Thapaliya at the the National Centre for Neuroimmunology and Emerging Diseases, Griffith University. corroborate this. 48 Referral for dietary assessment and the creation of a management plan may be beneficial. 5, 49 It is important to highlight that the use of nutrient supplementation yields inconsistent results. Encouraging sleep hygiene practices— that is, healthy sleep habits, behaviours and environmental factors that impact sleep quantity and quality— and salt regulation in the diet aims to manage sleep disturbances and orthostatic intolerance.
Pharmacological treatments
There is currently no evidence-based treatment for ME / CFS. The most widely used treatment approach employs medication to target specific symptoms( see table 4). Many individuals with ME / CFS report increased susceptibility to drug side effects. 28 Start at lower doses and work slowly towards the maximum tolerated dose. The recently updated NICE guidelines for ME / CFS highlight that the evidence for current commonly prescribed agents are of low quality and efficacy. 49
However, commonly prescribed medications for the treatment of cognitive disturbances and fatigue include modafinil, amantadine, and methylphenidate. 50-52 Commonly prescribed medications for sleep disturbances include trazodone, low-dose tricyclic antidepressants and cyclobenzaprine. 53 – 55 The treatment of chronic pain in ME / CFS follows the guidelines for the treatment
Table 3. Management strategies targeting specific symptoms
Symptom
Fatigue
Sleep disturbances
Gastrointestinal disturbances
Orthostatic intolerance
Management strategies
• Pacing
• Assistive devices and aides
• School / work flexibility
• Sleep hygiene practices
• Eye masks
• Ear plugs
• Dietary modification
• Nutrient supplementation
• Salt-regulated diet
Table 4. Treatment strategies targeting symptoms
Symptom Fatigue
Sleep disturbance
Pain
Orthostatic intolerance
Gastrointestinal disturbances
Comorbid secondary depression or anxiety
Treatment
• Modafinil
• Amantadine
• Methylphenidate
• Trazodone
• Low-dose tricyclic antidepressants
• Cyclobenzaprine
• Aspirin
• Paracetamol
• NSAIDs
• Amitriptyline
• Duloxetine
• Gabapentin
• Pregabalin
• Fludrocortisone
• Antispasmodic agents or laxatives( eg, linaclotide)
• Loperamide
• SSRI( eg, fluoxetine)
• SNRI( eg, duloxetine)
• Tricyclic antidepressants( eg, amitriptyline)
• Benzodiazepine( eg, clonazepam)
of neuropathic pain, using medications such as duloxetine, pregabalin, and amitriptyline. 49 The use of mitochondrial-targeting nutraceuticals as a treatment method in ME / CFS is unsupported because of insufficient evidence. The use of antimicrobial and probiotic intervention is also reported in ME / CFS. 56 – 58 However, its benefit is unsupported because of inconsistent research findings. 3, 5
Numerous off-label pharmaceuticals are used in ME / CFS as there are no approved pharmacological options: low-dose naltrexone( LDN)( 1-5mg) is a prime example. Research has demonstrated the benefit of LDN in reducing symptom presentation or severity in MS, fibromyalgia and Crohn’ s disease, as well as improving complications associated with cancer, for example fatigue and / or pain. 59 Individuals routinely taking LDN