What are the management options for chronic fatigue syndrome?

Management of Chronic Fatigue Syndrome

Cognitive behavioral therapy (CBT) and graded exercise therapy are the only interventions with proven efficacy for chronic fatigue syndrome and should be offered as first-line treatment, while pharmacologic options remain largely unproven and should be reserved for managing specific comorbid symptoms. 1, 2

Initial Assessment and Screening

• Screen fatigue severity at every clinical encounter using a 0-10 numeric rating scale, with scores ≥4 requiring comprehensive evaluation 1
• Obtain a detailed symptom history including onset timing, duration (must be >6 months for CFS diagnosis), pattern throughout the day, and factors that worsen or improve symptoms 1, 2
• Assess for the CDC diagnostic criteria: severe fatigue lasting >6 months PLUS at least four of the following: postexertional malaise, unrefreshing sleep, impaired memory/concentration, muscle pain, polyarthralgia, sore throat, tender lymph nodes, or new headaches 2
• Postexertional malaise is the most important symptom to identify, as it distinguishes CFS from other fatigue conditions and has critical treatment implications 3
• Evaluate the impact on daily activities and functional capacity, as similar fatigue scores can produce vastly different disability levels 1

Mandatory Laboratory Evaluation

When fatigue is moderate-to-severe (score ≥4), perform the following tests to exclude alternative diagnoses:

• Complete blood count with differential to evaluate for anemia 1
• Comprehensive metabolic panel to assess electrolyte disturbances and renal/hepatic function 1
• Thyroid function tests (TSH, free T4) to exclude hypothyroidism 1

Critical pitfall: There are no laboratory tests that confirm CFS—diagnosis is made solely on clinical criteria after excluding other conditions 4, 2

Assessment of Contributing and Comorbid Conditions

• Screen for depression and anxiety using validated tools, as these commonly co-occur and require specific treatment 1, 5
• Assess sleep quality and disturbances, including sleep apnea risk factors 1, 5
• Review all current medications for fatigue-inducing side effects 1
• Evaluate for fibromyalgia, irritable bowel syndrome, and headaches, which frequently coexist with CFS 5

Treatment Algorithm

Step 1: Address Identified Comorbidities First

• Treat anemia if hemoglobin is low using iron supplementation or erythropoietin as clinically indicated 1
• Initiate antidepressants (SSRIs or SNRIs) if depression is present—this is a Category 1 recommendation for fatigue management 1
• Implement cognitive behavioral therapy for insomnia (CBT-I) if sleep disturbance is identified, as this is more effective than pharmacologic sleep aids 1

Step 2: First-Line Nonpharmacologic Interventions (Proven Efficacy)

Cognitive Behavioral Therapy:

• Offer structured, tailored CBT delivered by trained providers to address thoughts, feelings, and behaviors related to fatigue 1, 2
• CBT has demonstrated moderate improvements in fatigue, distress, cognitive symptoms, mental health functioning, work and social adjustment, anxiety, and postexertional malaise 1, 2
• Web-based CBT versions are also effective if in-person therapy is not accessible 1
• Access to psychoeducational interventions should be discussed periodically based on patient needs 1

Graded Exercise Therapy (with critical caveats):

• WARNING: Exercise can be harmful to patients with CFS because it can trigger postexertional malaise 3
• If exercise is attempted, start at very low intensity (even 10-15 minutes of walking) and increase gradually based on tolerance 1, 2
• Prescribe moderate aerobic exercise 3-5 times weekly only if the patient does not have significant postexertional malaise 1
• Educate patients about pacing their activity to not exceed their limited energy capacity 3
• Graded exercise therapy has shown moderate improvements in fatigue levels when tolerated 2

Activity Management:

• Promote a consistent pattern of activity, rest, and sleep as the most important starting point 6
• Teach energy conservation techniques to maintain energy 7
• Address "boom and bust" activity patterns that worsen fatigue 7

Additional Nonpharmacologic Options:

• Consider mindfulness-based stress reduction programs, which show moderate effect sizes for enhancing quality of life 1
• Manual acupuncture can be considered as part of management 1
• Yoga or tai chi may provide benefits for physical functioning, quality of life, pain, fatigue, sleep quality, and mood 1

Step 3: Pharmacologic Interventions (Limited Evidence)

For Pain Management:

• Consider serotonin-norepinephrine reuptake inhibitors (SNRIs) for pain management and improved functional status 1
• Pregabalin may be offered for pain management 1

For Fatigue (Weak Evidence):

• Bupropion may be considered based on favorable results in open-label trials, though evidence is limited 1
• Modafinil may be effective for individuals with severe fatigue, though overall trial results were negative and should be used with caution 1

Medications to AVOID:

• Do NOT use opioid medications for CFS-related pain 1
• Do NOT use NSAIDs for chronic pain related to CFS 1
• Do NOT use stimulants for fatigue symptoms 1
• Do NOT use corticosteroids, antivirals, or antibiotics—they have shown no benefit 1
• Do NOT use mifepristone 1
• Paroxetine has not shown benefit and should not be used 1
• Progestational steroids have not demonstrated benefit 1

Step 4: Ongoing Monitoring and Adjustment

• Reassess fatigue severity, impact, and coping strategies at every visit using the same 0-10 scale 1
• Modify management strategies based on response and changes in clinical status 1
• Refer patients with unresolved fatigue despite comprehensive management to appropriate specialists 1

Multidisciplinary Care Coordination

• CFS is best managed by a multidisciplinary team led by primary care physicians with referrals to specialists based on predominant symptoms 1
• Consider involving rheumatologists for significant musculoskeletal symptoms, mental health professionals for CBT implementation, physical therapists for activity management, and integrative medicine specialists for complementary approaches 1

Critical Pitfalls to Avoid

• Do NOT assume fatigue will resolve spontaneously—it requires active management even when no underlying disease is found 1
• Do NOT skip nonpharmacologic interventions (CBT and graded exercise) in favor of medications, as they have the strongest evidence 1
• Do NOT prescribe exercise without warning about postexertional malaise and the need for pacing 3
• Do NOT focus exclusively on either physical or psychological aspects—CFS requires addressing both biological and psychosocial factors 1
• Develop mutual trust and collaboration as the first and most important task, as this is essential for successful management 6