What are the treatment options for chronic fatigue syndrome (CFS)?

Treatment of Chronic Fatigue Syndrome

Cognitive-behavioral therapy (CBT) and graded exercise therapy are the only evidence-based treatments that demonstrate moderate improvements in fatigue, functioning, and quality of life for chronic fatigue syndrome. 1, 2

Initial Assessment and Diagnosis

• Assess fatigue severity using a 0-10 numeric rating scale at every clinical encounter; scores ≥4 require comprehensive evaluation including physical, cognitive, and emotional domains, onset timing, daily patterns, and impact on daily functioning 3, 2
• Rule out alternative causes first: anemia (check CBC, consider iron supplementation or erythropoietin), hypothyroidism (TSH, free T4), depression (PHQ-9 screening, consider antidepressants if indicated), anxiety disorders, and sleep disturbances (evaluate for sleep apnea, insomnia) 3, 2
• Make a firm, positive diagnosis of CFS when no alternative physical or psychiatric disorder explains symptoms after thorough evaluation 4, 5
• Build and maintain a therapeutic alliance while explaining that CFS is a real clinical entity with biological and psychosocial components 1, 4

First-Line Non-Pharmacological Interventions

Cognitive-Behavioral Therapy

• Offer structured CBT delivered by trained providers as the primary intervention, focusing on identifying and modifying thoughts, feelings, and behaviors that perpetuate fatigue 1, 3, 2
• CBT should address catastrophic misinterpretations of symptoms, promote consistent activity patterns, and include problem-solving for current life difficulties 4, 5
• Web-based CBT programs can be considered when in-person therapy is not accessible 6

Graded Exercise Therapy

• Start with low-intensity aerobic exercise (walking, swimming, cycling) tailored to the patient's current functional capacity 3, 2
• Prescribe 3-5 sessions weekly, beginning at a level that does not exacerbate symptoms, then gradually increase duration and intensity based on tolerance 3, 7
• Combine aerobic exercise with resistance training when tolerated; both approaches show benefits 6, 1
• Critical caveat: Exercise must be carefully graded to avoid immune dysfunction and symptom exacerbation; patients should pace activities and respect physical limitations 7

Movement-Based Alternatives

• Consider tai chi or yoga as gentler alternatives for patients who cannot tolerate conventional exercise 1, 3, 2
• Tai chi performed twice weekly for 4 months significantly improves disability, quality of life, pain, fatigue, sleep quality, and mood 6, 1
• Yoga shows improvements in physical functioning at 3-month and 6-month follow-up 6

Complementary Interventions

• Offer mindfulness-based programs, which demonstrate moderate effect sizes for enhancing quality of life compared to waitlist or support group controls 6, 1, 2
• Manual acupuncture can be considered: 20-30 minute sessions three times weekly for 2-3 weeks, then twice weekly for 2 weeks, then weekly for 6 weeks 3, 2

Pharmacological Management

Medications to Consider

• Bupropion (norepinephrine-dopamine reuptake inhibitor) may be tried based on favorable results in open-label trials, though evidence is limited 6, 1, 2
• SNRIs (duloxetine, venlafaxine) can be considered for pain management and improved functional status 1, 3, 2
• Antidepressants may be tried on a pragmatic basis if comorbid depression is present, but should not be used specifically for fatigue reduction 2, 4

Medications to AVOID

• Do NOT use corticosteroids, antivirals, or antibiotics - no demonstrated benefit 6, 1, 3, 2
• Do NOT use stimulants (methylphenidate, modafinil) for fatigue symptoms 6, 1, 3, 2
• Do NOT use opioid medications for pain related to CFS 1, 3, 2
• Do NOT use NSAIDs for chronic pain management 1, 3, 2
• Do NOT use sedative-hypnotic drugs routinely due to FDA warnings 2
• Avoid alosetron and SSRIs specifically for symptom management 6
• Paroxetine has shown no benefit for CFS 6, 1
• Progestational steroids have no demonstrated benefit 6, 1
• Erythropoietin should be used with caution due to cardiovascular safety concerns and reduced disease control 6

Ongoing Management and Monitoring

• Reassess fatigue levels at every visit using the same 0-10 numeric scale to track treatment response 3, 2
• Promote consistent patterns of activity, rest, and sleep as the foundation of management 4, 7
• Encourage long-term physical activity as a lifestyle change rather than short-term intervention 1, 2
• Discuss access to psychoeducational interventions periodically based on patient needs 1, 2
• Refer to specialists (rheumatology, neurology, gastroenterology) when symptoms suggest specific organ system involvement or when fatigue remains unresolved despite comprehensive management 1, 3, 2

Common Pitfalls to Avoid

• Do not dismiss CFS as purely psychological - it involves both biological and psychosocial factors requiring integrated management 1, 4
• Do not prescribe vigorous exercise initially - this can worsen immune dysfunction and exacerbate symptoms 7
• Do not continue ineffective pharmacological trials - no medication has proven efficacy as monotherapy 5
• Do not allow prolonged complete rest - this leads to deconditioning and perpetuates disability 4, 7