What is the recommended management for chronic fatigue syndrome (myalgic encephalomyelitis)?

Management of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis

Offer cognitive-behavioral therapy (CBT) and mindfulness-based therapies as first-line interventions for ME/CFS, as these demonstrate the strongest evidence for improving health function, quality of life, and physical functioning. 1, 2

Core Diagnostic Requirements Before Treatment

• Confirm diagnosis requires profound fatigue lasting ≥6 months with substantial reduction in pre-illness activities, accompanied by postexertional malaise, unrefreshing sleep, and either cognitive impairment or orthostatic intolerance. 2, 3
• Systematically rule out anemia, hypothyroidism, depression, anxiety disorders, sleep disorders, electrolyte disturbances, and chronic infections before attributing symptoms to ME/CFS. 2, 3
• Screen fatigue severity using a 0-10 numeric rating scale at every visit, with scores ≥4 requiring comprehensive evaluation. 3

First-Line Non-Pharmacological Interventions

Behavioral Therapies (Strongest Evidence):

• Initiate structured cognitive-behavioral therapy as the primary intervention, which shows moderate to strong improvements in fatigue, distress, cognitive symptoms, and mental health functioning. 1, 2, 3
• Offer mindfulness-based stress reduction or mindfulness-based cognitive therapy, which demonstrate moderate effect sizes for enhancing quality of life compared to waitlist controls. 1, 2, 3
• Consider emotion-focused therapy for patients with prominent fibromyalgia-like or irritable bowel syndrome-like symptoms. 1, 2

Physical Activity Management (Critical Approach):

• Promote a consistent pattern of activity, rest, and sleep, starting physical activity at low intensity and gradually increasing based on tolerance to avoid postexertional malaise. 2, 3
• Introduce physical exercise gradually with careful titration, as it shows statistical benefits in improving quality of life and reducing pain but must be monitored to prevent symptom exacerbation. 2, 4
• Offer yoga or tai chi, which demonstrate significant improvements in physical functioning, quality of life, pain, fatigue, sleep quality, and mood, with longer treatment duration showing greater improvement. 2, 4

Important caveat: The evidence on graded exercise therapy remains controversial, with recent patient feedback suggesting that aggressive exercise programs can worsen symptoms. 5 Pacing of activities with strategic rest periods is the most important coping strategy to prevent post-exertional malaise. 6

Pharmacological Management

What NOT to Prescribe (Strong Recommendations Against):

• Avoid long-term opioid medications for chronic pain management in ME/CFS, as potential harms and burdens outweigh any theoretical benefits. 1, 2
• Avoid stimulants (methylphenidate, modafinil), corticosteroids, antivirals, or antibiotics, as they have no demonstrated benefit. 2, 3, 4
• Avoid NSAIDs for chronic pain related to ME/CFS. 1, 4
• Avoid mifepristone, which shows no benefit. 1, 4

Pharmacological Options with Limited Evidence:

• Consider serotonin-norepinephrine reuptake inhibitors (SNRIs, such as duloxetine) for pain management and improved functional status, particularly when fibromyalgia-like symptoms predominate. 1, 2
• Consider pregabalin for pain management, which provides 30-50% pain relief in fibromyalgia-like presentations. 1, 2
• Bupropion may be considered for fatigue management based on favorable results in open-label trials, though evidence remains limited. 2, 4

Critical note: There is insufficient evidence to recommend mirtazapine, selective serotonin reuptake inhibitors, or amitriptyline specifically for ME/CFS. 1

Complementary Approaches

• Offer manual acupuncture as part of management, with evidence supporting its effectiveness. 2, 4
• Consider biofeedback, manual musculoskeletal therapies, relaxation therapy, guided imagery, and hypnosis, though evidence is insufficient to make firm recommendations. 1

Management of Orthostatic Intolerance

• Address orthostatic intolerance (a core diagnostic feature) by increasing fluid and salt intake, considering compression stockings, and educating patients on gradual positional changes. 2
• Treat associated headaches according to standard migraine protocols when appropriate. 2

Monitoring and Follow-Up Strategy

• Reassess fatigue levels at every visit using the same 0-10 numeric scale to track response. 2, 3
• Regularly assess fatigue severity, impact, and coping strategies in clinical consultations. 2, 4
• Modify management strategies based on response and changes in clinical status. 3

Multidisciplinary Referral Algorithm

Primary care physicians should lead management as the central coordinator. 2, 4

Refer to specialists based on predominant symptoms:

• Mental health professionals for CBT, mindfulness-based therapy, and emotion-focused therapy. 2, 3, 4
• Physical therapists for structured, gradual exercise programs and activity pacing education. 2, 3
• Rheumatologists when significant musculoskeletal symptoms predominate. 2, 4
• Gastroenterologists when gastrointestinal symptoms (IBS-like) are prominent, affecting up to 40% of ME/CFS patients. 2, 4
• Sleep specialists for unrefreshing sleep and sleep disorder evaluation. 2, 3
• Neurologists for cognitive impairment assessment and headache management. 2, 4
• Integrative medicine specialists for complementary approaches and dietary supplement evaluation. 3, 4

Common Pitfalls to Avoid

• Do not prescribe opioids based on patient reports of severe pain alone without attempting evidence-based alternatives first (CBT, SNRIs, pregabalin). 2
• Do not recommend aggressive exercise programs without careful titration and monitoring for postexertional malaise. 6, 5
• Do not dismiss the illness as purely psychological; ME/CFS is a complex, multi-system condition with biological underpinnings. 6, 7
• Do not use immunoglobulin therapy (IVIG), as evidence demonstrates lack of net benefit. 4
• Remaining engaged in education and social connections is the best predictor of later functioning in adolescents with ME/CFS. 5