What are the treatment options for fatigue?

Treatment of Fatigue

Begin with nonpharmacologic interventions as first-line therapy, prioritizing moderate exercise programs, cognitive behavioral therapy (CBT), and mindfulness-based interventions, which have the strongest evidence for improving fatigue across all patient populations. 1, 2

Initial Assessment and Screening

• Screen all patients with fatigue using a 0-10 numeric rating scale, with scores ≥4 requiring comprehensive evaluation to identify underlying treatable causes 1, 3
• Conduct a focused evaluation including onset, pattern, duration, and factors that worsen or improve symptoms 1, 3
• Systematically assess for treatable contributing factors: pain, depression, anxiety, sleep disturbances, anemia, nutritional deficits, medication side effects, and endocrine dysfunction 1
• Obtain basic laboratory testing: complete blood count, comprehensive metabolic panel, and thyroid function tests 3

First-Line Nonpharmacologic Interventions (Category 1 Evidence)

Physical Activity

• Implement a structured, gradual exercise program as the primary intervention, targeting 150 minutes of moderate aerobic exercise weekly plus 2-3 strength training sessions 2
• Physical activity has the strongest evidence base (category 1) for treating fatigue during and after treatment 1, 2
• Start slowly and progressively increase intensity to improve functional capacity and activity tolerance 1

Psychosocial Interventions

• Prioritize CBT and mindfulness-based programs, particularly for post-treatment or persistent fatigue, as these demonstrate significant benefit in rigorous trials 1, 2
• CBT has category 1 evidence for reducing fatigue and can be delivered in-person or via web-based platforms for improved accessibility 1, 2
• Mindfulness-based approaches effectively reduce fatigue levels during and after treatment 1, 2

Energy Conservation Strategies

• Teach patients to maintain a daily/weekly diary to identify peak energy periods and plan essential activities accordingly 1, 2
• Counsel patients to prioritize activities, delegate nonessential tasks, and pace themselves throughout the day 1
• Limit daytime naps to less than one hour to avoid disrupting nighttime sleep 1

Sleep Hygiene

• Implement CBT for sleep (category 1 recommendation) for patients with sleep disturbances contributing to fatigue 2
• Establish consistent sleep-wake times, create a restful environment, and avoid caffeine, alcohol, and electronic devices before bedtime 2

Integrative Therapies

• Consider American ginseng for patients undergoing active treatment based on rigorous trial evidence 1
• Consider acupressure for patients with persistent post-treatment fatigue 1
• Tai chi and qigong show benefit during treatment; yoga demonstrates effectiveness after treatment completion 1

Pharmacologic Interventions

What NOT to Use

• Do not routinely recommend wakefulness agents (modafinil), psychostimulants (methylphenidate), or antidepressants specifically for fatigue treatment, as these have not proven effective for this indication 1
• These agents have likely failed because they do not directly target the underlying biologic mechanisms of fatigue 1

Limited Pharmacologic Options

• Consider corticosteroids (methylprednisolone) for short-term use in advanced cancer patients only 1
• Treat identified comorbidities with appropriate medications: levothyroxine for hypothyroidism, antidepressants for depression (fluoxetine, paroxetine, or sertraline), erythropoietin for anemia 1, 4

Treatment of Underlying Causes

• Address all identified treatable factors according to established practice guidelines before initiating symptom-specific fatigue interventions 1
• Optimize management of comorbid conditions including pain, depression, anxiety, sleep disorders, and nutritional deficits 1
• Review and adjust medications that may contribute to fatigue 1, 3

Follow-Up and Monitoring

• Schedule regular follow-up visits rather than sporadic urgent appointments for effective long-term management 4
• Reassess fatigue levels at each visit using the same screening tool to evaluate treatment effectiveness 3
• Adjust management strategies based on response and changes in clinical status 3
• Refer to specialists if fatigue persists despite comprehensive interventions 3

Critical Pitfalls to Avoid

• Do not pursue extensive laboratory testing beyond initial screening if results are normal; repeat testing affects management in only 5% of patients 4
• Avoid focusing exclusively on somatic causes, which can lead to overdiagnosis, as previously undiagnosed cancer accounts for only 0.6% of fatigue cases 5
• Do not prescribe exercise for patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), as it can trigger postexertional malaise and worsen symptoms 6
• Never dismiss patient education and counseling; inform patients that fatigue does not necessarily indicate disease progression 1