What is the first line of management for patients with Chronic Fatigue Syndrome (CFS)?

First-Line Management of Chronic Fatigue Syndrome

The first-line management for patients with Chronic Fatigue Syndrome is structured cognitive-behavioral therapy (CBT) combined with a gradual, individualized graded exercise program, both of which have the strongest evidence for improving fatigue, physical functioning, and quality of life. 1, 2, 3

Initial Assessment Requirements

Before initiating treatment, complete a thorough evaluation to establish the diagnosis and rule out alternative causes:

• Screen fatigue severity using a 0-10 numeric rating scale at every clinical encounter, with scores ≥4 requiring comprehensive evaluation including physical, cognitive, and emotional domains 2, 3
• Confirm diagnostic criteria: 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 3
• Systematically exclude treatable conditions including anemia, hypothyroidism, depression, anxiety disorders, sleep disorders, electrolyte disturbances, and chronic infections 3
• Assess comorbid psychiatric disorders such as depression or anxiety, which are mandatory to evaluate 4

Primary Treatment Interventions

Cognitive-Behavioral Therapy (First-Line)

CBT should be structured and tailored to address thoughts, feelings, and behaviors related to fatigue, demonstrating moderate improvements in fatigue, distress, cognitive symptoms, and mental health functioning 1, 2, 3. This intervention must be delivered by trained providers and focuses on:

• Promoting a consistent pattern of activity, rest, and sleep 3, 4
• Addressing catastrophic misinterpretations of symptoms 4
• Problem-solving current life difficulties 4
• Distinguishing between predisposing factors (lifestyle, work stress), triggering factors (viral infection, life events), and perpetuating factors (cerebral dysfunction, sleep disorder, depression, inconsistent activity) 4

Graded Exercise Therapy (First-Line)

Physical activity should start at low intensity and gradually increase based on tolerance, with the goal of avoiding exacerbations while improving physical functioning 2, 3, 5. The approach includes:

• Begin with moderate aerobic exercise such as walking, swimming, or cycling, 3-5 times weekly, tailored to functional status 2
• Design programs to cater for individual physical capabilities and account for the fluctuating nature of symptoms 5
• Encourage patients to pace activities and respect physical and mental limitations to avoid immune dysfunction from too-vigorous exercise 5
• Consider gentler alternatives including tai chi, qigong, or yoga, which show significant improvements in physical functioning, quality of life, pain, fatigue, and sleep quality 1, 2

Complementary Interventions

Mindfulness-based programs show moderate effect sizes for enhancing quality of life and may be effective in reducing fatigue 1, 2. These can be offered alongside CBT and exercise therapy.

Manual acupuncture can be considered with sessions three times weekly for 2-3 weeks, then twice weekly for 2 weeks, then weekly for 6 weeks 2.

Pharmacological Considerations

Medications to Consider

• Bupropion may be considered based on favorable results in open-label trials for fatigue management 1, 2
• SNRIs (such as duloxetine) can be considered for pain management and improved functional status 1, 3
• Pregabalin may be offered for pain management 1

Medications to Avoid

Do not use the following medications as they have no demonstrated benefit or potential harm:

• Avoid opioid medications for pain related to CFS 1
• Avoid NSAIDs for chronic pain related to CFS 1, 2
• Avoid corticosteroids, antivirals, or antibiotics as they show no benefit 1, 3
• Avoid stimulants for fatigue symptoms 1, 2
• Avoid mifepristone 1
• Avoid sedative-hypnotic drugs routinely due to FDA warnings 2

Ongoing Management and Monitoring

• Reassess fatigue levels at every visit using the same 0-10 numeric scale to track response 2, 3
• Modify management strategies based on response and changes in clinical status 2
• Incorporate regular assessment of fatigue severity, impact, and coping strategies into clinical consultations 1, 2
• Discuss access to psychoeducational interventions periodically based on patient needs 1
• Encourage long-term physical activity as a lifestyle change 1

Critical Pitfalls to Avoid

The most important pitfall is failing to establish mutual trust and collaboration with the patient before initiating treatment 4. Additionally:

• Do not dismiss the illness as "not real" - successful rehabilitation does not indicate the illness is not genuine 6
• Do not prescribe exercise programs that are too vigorous, as this can promote immune dysfunction and increase symptoms 5
• Do not focus exclusively on either physical or psychological aspects - the condition requires addressing both biological and psychosocial factors 1
• Do not use antidepressants specifically for fatigue reduction unless treating comorbid depression 2