What are the treatment options for chronic fatigue syndrome?

Treatment for Chronic Fatigue

Start with cognitive-behavioral therapy (CBT) and graded exercise therapy as first-line treatments for chronic fatigue syndrome, as these interventions have the strongest evidence for reducing fatigue severity and improving quality of life. 1, 2

Initial Assessment

Before initiating treatment, screen fatigue severity using a 0-10 numeric rating scale at every clinical encounter, with scores ≥4 requiring comprehensive evaluation. 3 Assess the multidimensional character including physical, cognitive, and emotional domains, and document impact on daily activities. 3

Evaluate and treat contributing factors first:

• Check complete blood count to identify anemia (treat with iron or erythropoietin if present) 1, 3
• Obtain thyroid function tests to exclude hypothyroidism 1, 3
• Screen for depression and anxiety (antidepressants are Category 1 recommendation if depression is present) 3, 4
• Assess sleep quality and treat insomnia with CBT for insomnia if identified 1, 3
• Review all medications for fatigue-inducing effects (β-blockers, narcotics, antihistamines) 1

First-Line Non-Pharmacological Interventions

Cognitive-Behavioral Therapy:

• Offer structured CBT delivered by trained providers, which demonstrates moderate improvements in fatigue, distress, cognitive symptoms, and mental health functioning 1, 2
• CBT should address thoughts, feelings, and behaviors related to fatigue 2
• The American Academy of Sleep Medicine recommends CBT specifically for chronic insomnia, which commonly co-occurs with fatigue 1
• Web-based versions of effective in-person programs also show benefit and may be more accessible 1

Graded Exercise Therapy:

• Prescribe tailored physical activity starting at low intensity and gradually increasing based on tolerance 3, 5
• Exercise therapy probably reduces fatigue at end of treatment (moderate-certainty evidence) with an effect size of -3.4 points on a 0-33 scale 5
• Recommend moderate aerobic exercise (walking, swimming, cycling) 3-5 times weekly, tailored to functional status 1, 3
• Combine aerobic and resistance training for optimal benefits on strength, energy, and fitness 2
• Begin with discussions and low levels of activities if the patient is significantly deconditioned 1

Alternative Movement-Based Therapies:

• Consider tai chi, qigong, or yoga as gentler alternatives, which show significant improvements in physical functioning, quality of life, pain, fatigue, and sleep quality 1, 6
• Yoga is specifically recommended for cancer survivors with fatigue 1

Complementary Interventions

Mindfulness-Based Therapies:

• Offer mindfulness-based programs, which show moderate effect sizes for enhancing quality of life 2
• Mindfulness-based stress reduction may be effective in reducing fatigue 1

Acupuncture:

• 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) 1, 2
• Meta-analysis of 10 RCTs showed marked effect on fatigue, particularly for breast cancer patients, though adverse events were reported in six studies 1

Sleep Optimization:

• Implement stimulus control: go to bed when sleepy, maintain regular sleep/wake times, get out of bed after 20 minutes if unable to fall asleep 1
• Practice sleep restriction: avoid long or late afternoon naps, limit total time in bed 1
• Establish sleep hygiene: avoid caffeine after noon, create dark/quiet/comfortable environment 1

Pharmacological Considerations

Medications That May Help:

• Bupropion may be considered based on favorable results in open-label trials 2, 6
• Serotonin-norepinephrine reuptake inhibitors (SNRIs) can be considered for pain management and improved functional status 2
• Pregabalin may be offered for pain management 2

Medications to Avoid:

• Do not use antidepressants specifically for fatigue reduction (paroxetine showed no benefit) 1, 2, 6
• Do not use corticosteroids, antivirals, or antibiotics (no demonstrated benefit) 2, 6
• Do not use stimulants for fatigue symptoms 2, 6
• Do not use opioids or NSAIDs for chronic pain related to chronic fatigue 2, 6
• Do not use sedative-hypnotic drugs routinely due to FDA warnings regarding severe allergic reactions, complex sleep-related behaviors, and risks of daytime sleepiness, dependency, and rebound insomnia 1

Ongoing Management

Monitoring:

• Reassess fatigue levels at every visit using the same 0-10 numeric scale to track response 3
• Fatigue should be routinely monitored as part of clinical care 2
• Regular assessment of fatigue severity, impact, and coping strategies should be incorporated into clinical consultations 1, 6

Treatment Adjustments:

• Modify management strategies based on response and changes in clinical status 3
• Access to psychoeducational interventions should be discussed periodically based on patient needs 2
• Encourage long-term physical activity as a lifestyle change 2
• Refer patients with unresolved fatigue despite comprehensive management to specialists 3

Common Pitfalls to Avoid

• Do not dismiss fatigue as purely psychological; it encompasses multiple biological, psychological, and social factors 1
• Do not prescribe exercise without assessing conditioning level first, as significantly deconditioned patients need gradual progression 1
• Do not overlook comorbidities (cardiac, pulmonary, renal, hepatic, neurologic, endocrine dysfunction) that may contribute to fatigue 1
• Do not use polypharmacy approaches without evidence, as medication interactions increase fatigue risk 1