Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ONGOING

all patients

1st line – ongoing multidisciplinary support

Back
ONGOING
|
all patients
1st line – 

ongoing multidisciplinary support

National Institute for Health and Care Excellence (NICE) guidance suggests that good care for people with ME/CFS results from access to an integrated team of health and social care professionals trained and experienced in managing ME/CFS.[8]

Primary care clinicians play a key role in management of patients with ME/CFS, typically retaining responsibility for long-term care and monitoring, in partnership with the ME/CFS specialist team in secondary care.

A key role of the primary care clinician is to liaise with other health, social care, and educational professionals in response to specific evolving patient needs, and to facilitate access to resources in the community (e.g., physiotherapy, occupational therapy, dietetic support, and district nursing staff visits) as guided by disease severity and individual need.[10]​ 

NICE recommends that adults with ME/CFS receive a review of their care and support plan in primary care at least once a year; review at least every 6 months is recommended for children and young people with ME/CFS. More frequent primary care reviews should be arranged as needed, with the interval dependent on the severity and complexity of symptoms, and the effectiveness of symptom management.[8]  

Initial treatment should be individualised based on the spectrum of the most severe complaints. One approach is to focus on the most severe symptoms and address each one at a time through a series of scheduled visits. A possible strategy may be to provide counsel to patients every 3 months and to reassess any other health issues and treatable diseases.

Multidisciplinary support may encompass support for activities of daily living, developing self-management strategies, guidance on managing potential relapse, and encouraging flexible work commitments. It is essential that service providers are proactive and recommend flexibility for those with severe or very severe ME/CFS: specifically, by offering home visits or online or phone consultations, and by supporting applications for disability aids and appliances.[8]

The provision of reliable educational materials may be useful, and can help with empowering the patient for self-management. NHS: ME/CFS Opens in new window

Consider – energy management/pacing

Back
ONGOING
|
all patients
Consider – 

energy management/pacing

Additional treatment recommended for SOME patients in selected patient group

The concept of an 'energy envelope', as outlined by NICE guidelines, provides people with ME/CFS with a strategy to manage their exertional tolerance.[8][10]​​​​​​ The energy envelope refers to the amount of energy that the patient has available to perform all of their daily activities.[183] The size of the energy envelope needs to be defined on a daily basis because resources and tolerance can vary from day to day and depending on other life stressors. Exceeding the energy envelope depletes these reserves and leads to post-exertional worsening of symptoms and of cognitive and physical functioning. The patient and practitioner can work together to recognise personal energy limits and set reasonable limits on activities. 

'Pacing' refers to a self-management strategy whereby individuals divide activities into smaller parts with interspersed rest intervals in order to remain within the limits of the envelope.[23][183][193]​​​​​​​​ As a general guide, patients are encouraged to keep their heart rate at less than 70% of the age-predicted maximum. Planned organisation of efforts is important to avoid doing harm by exceeding the limitations of the energy envelope.[194] While pacing may introduce a coping strategy for some patients, this is not a therapy and may not improve or alleviate the symptoms of ME/CFS, and should be undertaken with the guidance of a physician or nurse practitioner. Successful pacing is believed to be the most beneficial management strategy for ME/CFS according to NICE, the US Centers for Disease Control and Prevention (CDC), and the US National Institutes of Health.[8]​​[145][192]​​​​​​ The aim is to optimise the patient’s ability to maintain activities of daily living and community/society participation. 

Note: NICE defines graded exercise therapy (GET) as 'establishing a baseline of achievable exercise or physical activity and then making fixed incremental increases in the time spent being physically active. It is a therapy based on the deconditioning and exercise avoidance theories of ME/CFS'. It is important to highlight that structured GET is not recommended to accompany pacing strategies.[8]​ However, patients with ME/CFS may tolerate an individualised activity plan developed in collaboration with knowledgeable and experienced professionals.[23] The activity plan must aim to minimise the negative effects of exertion on impaired aerobic and cognitive function.

See Physiotherapist or occupational therapist referral.

Consider – environmental modifications

Back
ONGOING
|
all patients
Consider – 

environmental modifications

Additional treatment recommended for SOME patients in selected patient group

People with ME/CFS commonly report sensitivities to light, noise, and odours, and are often diagnosed with comorbid multiple chemical sensitivities. Therefore, it may be pertinent to discuss encouraging the following to limit impact of the environment on symptoms: a perfume- and chemical-free environment; use of eye masks and ear plugs.

Consider – psychosocial interventions

Back
ONGOING
|
all patients
Consider – 

psychosocial interventions

Additional treatment recommended for SOME patients in selected patient group

Cognitive behavioural therapy (CBT) may be offered to adults, children, and young people with ME/CFS who would like to use it to support them in managing their symptoms.[8] Mindfulness is an alternative psychosocial approach recommended for symptom relief in ME/CFS by European ME/CFS guidance.[10]

Protocols for techniques including CBT or a mindfulness approach are not standardised as there are significant differences in outcomes between different countries and different studies depending on their inclusion criteria. Studies of CBT in people with ME/CFS report significant improvements in mental health scores, fatigue scores, and 6-minute walking, but effect sizes were low and were not corrected for multiple comparisons.[195]​​​​[196]​​​​​ Internet-supported CBT is an emerging approach that has shown initially promising results, and that may help facilitate access for people with difficulties attending face-to-face appointments.[197]​ In routine medical practice CBT has not yielded clinically significant long-term benefits in ME/CFS.[196]

It is important to highlight that the offer of psychosocial interventions does not reflect the belief that ME/CFS is of psychological aetiology; psychosocial interventions should be offered with considerable care to avoid distress.[198]​ 

Rather, these techniques have been beneficial in people suffering other chronic diseases. For example, in patients who have been chronically ill, mindfulness skills have a positive effect on depression, mood, and activity level.[199] This approach facilitates the person with ME/CFS to identify unhelpful negative emotion-provoking thoughts, dysfunctional behaviours, and cognitive patterns, and uses a goal-oriented, systematic procedure to enhance self-esteem. CBT may help in dealing with a new diagnosis of ME/CFS, improve coping strategies, and assist with rehabilitation. CBT should be offered not as a 'cure' for ME/CFS but to support people to manage their symptoms and to refine self-management strategies to improve functioning and quality of life.[8]

Consider – management of fatigue, PEM, and cognitive disturbance

Back
ONGOING
|
all patients
Consider – 

management of fatigue, PEM, and cognitive disturbance

Additional treatment recommended for SOME patients in selected patient group

According to the CDC, NICE, and the Mayo Clinic, pacing provides the most beneficial approach to reducing the burden of fatigue and post-exertional malaise (PEM) in ME/CFS.[8][192][202]​​​​​​​​ 

See Energy management/pacing.

Other supportive measures may include: assistive devices and home health aides; school/work flexibility.

Consider – management of sleep alteration

Back
ONGOING
|
all patients
Consider – 

management of sleep alteration

Additional treatment recommended for SOME patients in selected patient group

Sleep difficulties are a major problem, and initial management is to address sleep hygiene. NICE guidance recommends personalised sleep management advice for people with ME/CFS.[8]

If this is ineffective, evaluate for underlying causes of sleep problems. In the general adult population, CBT for insomnia (CBT-I) is typically recommended as the first-line management option for chronic insomnia.[203] Normalisation of the sleep/wake rhythm begins by stopping daytime napping and proceeds to improving the quality of sleep through relaxation therapy. Instruction is provided to prevent relapse.

See Insomnia.

Consider – management of pain

Back
ONGOING
|
all patients
Consider – 

management of pain

Additional treatment recommended for SOME patients in selected patient group

Rehabilitation and allied health services may provide non-pharmacotherapeutic approaches to pain including acupuncture and massage if touch is tolerated by the patient.[10]​

NICE guidance for ME/CFS refers to the treatment of headache and neuropathic pain detailing the following.

For headache: a choice of aspirin, paracetamol, or non-steroidal anti-inflammatory drugs (NSAIDs).

For other pain in ME/CFS: a choice of amitriptyline, duloxetine, gabapentin, or pregabalin.[8]​  

NICE made the decision not to recommend any pharmacological interventions specific to pain in ME/CFS, citing a lack of evidence. The options above referred to by NICE are consistent with those recommended for pain in ME/CFS in European guidance by EUROMENE.[10] However, it is important to highlight that there is limited evidence for these pharmacotherapeutic agents for the treatment of pain in ME/CFS through randomised controlled trials. Note that pain medications improve pain but do not treat systemic hyperalgesia.

Referral to specialist pain services may be required if pain does not respond to initial management.[8]​ If the initial treatment is not tolerated, further pharmacological recommendations for the management of pain in fibromyalgia may be used to guide treatment, in conjunction with specialist pain/ME/CFS/fibromyalgia services.[204][205]

See Fibromyalgia.

Consider – management of orthostatic intolerance

Back
ONGOING
|
all patients
Consider – 

management of orthostatic intolerance

Additional treatment recommended for SOME patients in selected patient group

Orthostatic intolerance even without postural orthostatic tachycardia is a major limiting condition that can be treated with compression stockings, positional changes, and salt loading.[10][207]​ Advice on diet, daily activities, and activity support should be tailored to the individual, taking into account their other ME/CFS symptoms.[8]​  

Referral to secondary care is warranted if symptoms are severe or worsening, or there are concerns that another condition may be the cause.[8] 

There may be a role for fludrocortisone, pyridostigmine, or other drugs used for orthostatic instability in ME/CFS.[10][208]

NICE advises that pharmacotherapy for orthostatic intolerance in people with ME/CFS should only be prescribed or overseen by a clinician with expertise in orthostatic intolerance; this is because pharmacotherapy may worsen other symptoms in people with ME/CFS.[8] 

See Postural orthostatic tachycardia syndrome.

Consider – management of gastrointestinal symptoms

Back
ONGOING
|
all patients
Consider – 

management of gastrointestinal symptoms

Additional treatment recommended for SOME patients in selected patient group

Symptoms akin to irritable bowel syndrome and food intolerances are commonly reported in ME/CFS.[10] Monitor patients for malnutrition and unintentional weight loss or gain.[8] Dietary modification and food avoidance practices may be recommended in specific circumstances with support from a dietician.[10] However, it should be highlighted that randomised controlled trials examining the effects of dietary interventions in ME/CFS have yielded inconsistent results.[209] Dietary management is not offered as a cure or treatment, but rather as part of a management plan with the aim of minimising the effects of diet on gastrointestinal manifestations. 

The NICE guidelines for ME/CFS encourage referring people with ME/CFS for a dietetic assessment and creation of a management plan by a dietitian with a special interest in ME/CFS, if they are: losing weight and at risk of malnutrition; gaining weight; following a restrictive diet.[8] 

In the event that food avoidance practices and dietary management are not successful, pharmacological interventions may be utilised to improve gastrointestinal symptoms.

See Irritable bowel syndrome.

Consider – management of co-existing anxiety or depression

Back
ONGOING
|
all patients
Consider – 

management of co-existing anxiety or depression

Additional treatment recommended for SOME patients in selected patient group

For comorbid depression or anxiety, CBT ± antidepressants may be helpful, in keeping with the management of depression and anxiety for the general population.[210][211]​ Given that some patients with ME/CFS may have hypersensitivity to medication adverse effects, starting drug treatment at a low sub-therapeutic dose, and gradually increasing to therapeutic levels over time as tolerated, is usually recommended.[201]

There is no evidence to suggest that antidepressants help with PEM, cognitive dysfunction, orthostatic intolerance, or other cardinal features of ME/CFS. Choice of antidepressant drug for comorbid depression or anxiety should be based on the treatment history, the adverse-effect profile of the drug, and the patient's initial response to treatment.

Possible adverse effects of standard treatments for depression include sedation, orthostatic hypotension, and increased appetite and weight gain, which may worsen fatigue and autonomic lability in some patients. Based on clinical experience, difficulties in achieving necessary amounts of exercise mean that people with ME/CFS may experience exaggerated adverse effects such as weight gain that may promote iatrogenic type 2 diabetes and metabolic syndrome with associated long-term health consequences.

Improvements with drug therapy may take several weeks, but more severe levels of depression may predict a slower treatment response.[213]

A suicide evaluation is standard practice for all patients who appear to be clinically depressed or highly stressed. In one UK-based study, suicide-specific mortality was found to be significantly increased in patients with ME/CFS compared with the general population, indicating the need for physician awareness and compassionate care.[212] Mental health crisis management and/or referral to secondary care may be indicated in the case of severe depression (e.g., in the presence of suicide risk).

See Depression in adults, Depression in children, Generalised anxiety disorder, and Suicide risk mitigation.

Consider – physiotherapist or occupational therapist referral

Back
ONGOING
|
all patients
Consider – 

physiotherapist or occupational therapist referral

Additional treatment recommended for SOME patients in selected patient group

NICE recommends referring people with ME/CFS to a physiotherapist or occupational therapist working in an ME/CFS specialist team if they: have difficulties caused by reduced physical activity or mobility; feel ready to progress their physical activity beyond their current activities of daily living; or would like to incorporate a physical activity or exercise programme into managing their ME/CFS.[8]

Assessment and access to occupational therapy may be required to facilitate home adaptation for people with moderate to very severe ME/CFS. These aids may include, but are not limited to: disability parking, wheelchairs, motorised scooters, shower chairs, stairlifts.

Physiotherapy may support physical symptoms of ME/CFS. Physiotherapy is offered as a management approach and is not a proven treatment option.

It is important that any physiotherapy or activity/exercise plan is carefully individualised to the patient and is overseen by an ME/CFS specialist team; the aim is to to minimise the negative effects of exertion on impaired aerobic and cognitive function.[8]

2nd line – referral to secondary care

Back
ONGOING
|
all patients
2nd line – 

referral to secondary care

Referral to the person's named contact in the ME/CFS secondary care team is required if new or deteriorating aspects of their condition develop.[8] 

In the event that a person with ME/CFS desires pharmacological intervention when rehabilitation and support strategies have been unsuccessful, pharmacological interventions targeting fatigue and cognitive disturbances may be considered by a specialist in ME/CFS following risk-benefit analysis.

The NICE guidelines for ME/CFS highlight that the evidence for these agents is limited and of very low quality. Ultimately, NICE recommended that many of these pharmaceuticals should not be used for the treatment of ME/CFS.[8]

It is essential to highlight that no pharmacological interventions can be offered as a treatment or cure for ME/CFS; however, based on clinical experience, they may provide some relief.

Given that some patients with ME/CFS may have hypersensitivity to medication adverse effects, starting drug treatment at a low sub-therapeutic dose, and gradually increasing to therapeutic levels over time as tolerated, is usually recommended.[201]

Further-line pharmaceutical agents that are sometimes prescribed in secondary care for cognitive disturbances and fatigue (based on very low-quality evidence) include modafinil, amantadine, and methylphenidate.[214][215][216][217]​​​​​[218] Note that amantadine in particular is associated with several adverse events, and may be poorly tolerated.[217]

Further-line agents that are sometimes prescribed for sleep disturbance include trazodone, low-dose tricyclic antidepressants, and cyclobenzaprine. Evidence on these drugs specific to ME/CFS is lacking.[219][220][221][222]

back arrow

Choose a patient group to see our recommendations

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

Use of this content is subject to our disclaimer