Management of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)
Cognitive-behavioral therapy (CBT) is the primary first-line treatment for ME/CFS, demonstrating the strongest evidence for improving health function, quality of life, and physical functioning. 1, 2, 3
Diagnostic Confirmation Before Treatment
Before initiating treatment, confirm the diagnosis requires all of the following present for ≥6 months: profound fatigue with substantial reduction in pre-illness activities, postexertional malaise, unrefreshing sleep, and either cognitive impairment or orthostatic intolerance. 1, 2
Systematically exclude treatable mimics including anemia, hypothyroidism, depression, anxiety disorders, sleep disorders, electrolyte disturbances, and chronic infections before attributing symptoms to ME/CFS. 1, 2
Treatment Algorithm: Step-by-Step Approach
Step 1: Non-Pharmacological Foundation (Start Here for All Patients)
Initiate structured CBT as the primary intervention, which should be tailored to address thoughts, feelings, and behaviors related to fatigue, with demonstrated moderate improvements in fatigue, distress, cognitive symptoms, and mental health functioning. 1, 3, 4
Implement activity pacing (not graded exercise therapy) as the core management strategy, promoting consistent patterns of activity, rest, and sleep, starting physical activity at low intensity and gradually increasing only based on tolerance to avoid postexertional malaise. 1, 3
Step 2: Complementary Mind-Body Interventions
Add mindfulness-based stress reduction or mindfulness-based cognitive therapy, which show moderate effect sizes for enhancing quality of life compared to control groups. 1, 3
Consider 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. 1, 3
Step 3: Exercise Prescription (Critical Nuance Required)
For patients with orthostatic intolerance or exercise intolerance, prescribe only recumbent or semi-recumbent exercise (rowing, swimming, or cycling)—never upright exercise initially, as upright exercise worsens fatigue and causes postexertional malaise. 5
Start with 5-10 minutes daily of recumbent exercise at an intensity allowing full-sentence speech, increasing by only 2 additional minutes per week as tolerance improves. 5
Transition to upright exercise only after orthostatic intolerance resolves completely. 5
Step 4: Orthostatic Intolerance Management
Increase salt intake to 5-10 grams (1-2 teaspoons) daily through liberalized dietary sodium—avoid salt tablets due to nausea risk—and increase fluid intake to 3 liters daily of water or electrolyte-balanced fluids. 5
Elevate the head of the bed with 4-6 inch (10-15 cm) blocks during sleep and use waist-high compression stockings to support central blood volume. 5, 1
Avoid alcohol, caffeine, large heavy meals, and excessive heat exposure, which contribute to dehydration and worsen orthostatic symptoms. 5
Pharmacological Management (Only After Non-Pharmacological Approaches)
For Pain Management
Consider duloxetine (SNRI) or pregabalin as first-line pharmacological options for pain, both providing 30-50% pain relief and improvements in Patient Global Impression of Change scores. 1, 3
For Refractory Fatigue with Depressive Features
Bupropion may be considered, though evidence is limited to open-label trials. 1, 3
Medications to Avoid
Never prescribe opioids (including hydrocodone) for ME/CFS pain, as the VA/DoD guideline recommends against long-term opioid use because harms and burdens outweigh any theoretical benefits in this population. 1
Avoid stimulants (methylphenidate, modafinil), corticosteroids, antivirals, antibiotics, and NSAIDs, as they have no demonstrated benefit and harms outweigh benefits. 1, 2
Complementary Approaches
Consider manual acupuncture as part of management, with evidence supporting improvements in quality of life both immediately after treatment and up to 3 months post-treatment. 1, 3
Monitoring Protocol
Assess fatigue severity at every visit using a 0-10 numeric rating scale (scores ≥4 require comprehensive evaluation), tracking response to interventions and modifying management strategies based on clinical changes. 1, 2, 3
Regularly evaluate fatigue impact, coping strategies, and treatment response, considering referral to mental health professionals, physical therapists, rheumatologists, sleep specialists, or integrative medicine specialists for comprehensive management. 1, 2, 3
Critical Pitfalls to Avoid
Do not prescribe traditional graded exercise therapy with upright exercise for patients with orthostatic intolerance, as this worsens postexertional malaise—the UK NICE guidelines specifically caution against this approach. 5
Do not prescribe hydrocodone or other opioids based on patient reports of severe pain alone without first attempting CBT, SNRIs, or pregabalin, as the guideline-supported pathway requires documenting trials of evidence-based alternatives first. 1
Do not dismiss the severity of disability—ME/CFS can be severely disabling and cause patients to be bedridden, yet 80% struggle to get a diagnosis because physicians lack training in recognition and management. 6