What are the management and treatment options for fatigue?

Management and Treatment of Fatigue

Clinicians should recommend exercise (aerobic, resistance, or combination) and cognitive behavioral therapy as first-line interventions for fatigue management, with regular screening using a 0-10 numeric rating scale at every clinical encounter. 1, 2

Initial Assessment and Screening

• Screen fatigue severity at every clinical visit using a 0-10 numeric rating scale, with scores ≥4 requiring comprehensive evaluation. 2
• Assess fatigue onset, pattern, duration, changes over time, and impact on daily activities and functional capacity. 3, 2
• Evaluate coping strategies and the patient's understanding of their illness, as these inform treatment planning. 1, 4
• Do not assume responsibility for raising fatigue lies solely with the patient—health professionals must proactively assess this symptom. 1

Comprehensive Evaluation for Moderate-to-Severe Fatigue (Score ≥4)

Mandatory Laboratory Testing

• Complete blood count with differential to evaluate for anemia. 2
• Comprehensive metabolic panel to assess electrolyte disturbances and renal/hepatic function. 2
• Thyroid function tests (TSH, free T4) to exclude hypothyroidism. 2

Assessment of Contributing Factors

• Identify and address all treatable contributing factors first: pain, depression, anxiety, emotional distress, sleep disturbance, nutritional deficits, activity level, anemia, medication adverse effects, and comorbidities. 1, 2
• Screen for depression and anxiety using validated tools, as these commonly co-occur with fatigue and require specific treatment. 2
• Evaluate sleep quality and disturbances, including sleep apnea risk factors. 2
• Review all current medications for fatigue-inducing side effects. 2

Treatment Algorithm

Step 1: Physical Activity Interventions (First-Line, Strongest Evidence)

Physical activity is the most effective intervention for managing fatigue and should be offered to all patients as part of clinical care. 1, 3

• Recommend 150 minutes of moderate aerobic exercise (such as fast walking, cycling, or swimming) per week plus 2-3 strength training sessions weekly. 1, 3
• Exercise may be supervised or unsupervised, tailored to the patient's current sedentary behaviors, disease activity, comorbidities, disability, preferences, and goals. 1
• Start at low intensity (even 10-15 minutes of walking provides benefit initially) and gradually increase based on tolerance. 2
• Walking programs are generally safe for most patients and can begin after physician consultation without formal exercise testing. 1
• Patients at higher risk of injury (those with neuropathy, cardiomyopathy, or severe fatigue interfering with function) should be referred to a physical therapist or exercise specialist. 1
• Encourage long-term physical activity as a lifestyle change, not just a time-limited intervention. 1

Step 2: Psychoeducational and Cognitive Behavioral Interventions (First-Line)

Cognitive behavioral therapy (CBT) should be recommended to manage fatigue symptoms, delivered in person or via web-based programs. 1, 2

• CBT addresses thoughts, feelings (physical and emotional), and behaviors in relation to fatigue, going beyond information provision alone. 1
• Psychoeducational interventions should be structured, time-limited, and tailored to individual needs. 1
• Access to psychoeducational interventions should be discussed periodically and be needs-based, not restricted based on previous offers or uptake. 1
• Refer patients to psychosocial service providers who specialize in the relevant condition and are trained to deliver empirically based interventions. 1

Step 3: Mindfulness-Based and Mind-Body Interventions

Mindfulness-based programs (including mindfulness-based stress reduction, mindfulness-based cognitive therapy, and mindful awareness practices) should be recommended to reduce fatigue severity. 1, 3

• These programs may be delivered in person or via web-based platforms. 1
• Yoga may be recommended to reduce fatigue severity, especially in women with breast cancer. 1
• Acupressure and moxibustion may be considered for managing fatigue symptoms. 1
• Additional mind-body interventions with some evidence include acupuncture, though more research is needed. 1

Step 4: Sleep Management

CBT for insomnia (CBT-I) should be implemented if sleep disturbance is identified, as it is more effective than pharmacologic sleep aids. 2

• Establish consistent sleep and wake times, create a restful sleep environment, and avoid caffeine, alcohol, and electronic devices before bedtime. 3
• Promote a consistent pattern of activity, rest, and sleep as a foundation for fatigue management. 4

Step 5: Activity Pacing and Energy Conservation

• Teach patients to plan activities according to energy levels using a daily/weekly diary. 3
• Prioritize essential activities and schedule them during peak energy periods. 3
• Address "boom and bust" activity patterns that can perpetuate fatigue. 1
• Regular self-monitoring of fatigue levels using a diary can help document improvement. 3

Step 6: Pharmacologic Interventions (Limited Role)

Pharmacologic options have limited evidence and should be reserved for patients with persistent fatigue despite addressing underlying causes and implementing nonpharmacologic interventions. 2

• Clinicians should NOT routinely recommend psychostimulants (such as methylphenidate) or wakefulness agents (such as modafinil or armodafinil) to manage fatigue in adults who have completed cancer treatment. 1
• Evidence for these agents is limited to patients with advanced disease or those receiving active treatment, not disease-free patients after treatment. 1
• If depression is present, initiate antidepressants (SSRIs or SNRIs) as this is a Category 1 recommendation for fatigue management. 2
• Corticosteroids may be considered for short-term use only in advanced disease or severe cases, but toxicity limits long-term use. 2
• Small pilot studies have evaluated supplements (ginseng, vitamin D), but there is no consistent evidence of effectiveness. 1

Ongoing Monitoring and Follow-Up

• Reassess fatigue levels at every visit using the same 0-10 scale to track response to treatment. 2
• Observe and re-evaluate patients regularly to determine whether treatment is effective or needs to be reassessed. 1
• Modify management strategies based on response and changes in clinical status. 2
• Schedule regular follow-up visits rather than sporadic urgent appointments for effective long-term management. 5
• If fatigue persists despite comprehensive interventions, refer to specialists (endocrinology, psychiatry, physiatry). 3, 2

Critical Pitfalls to Avoid

• Do not assume fatigue will resolve spontaneously—it requires active management even when underlying disease is controlled. 2
• Do not skip nonpharmacologic interventions (exercise and CBT) in favor of medications, as they have the strongest evidence. 2
• Do not make assumptions about when someone might be impacted by fatigue based on disease activity levels—fatigue can be severe even in remission or low disease states. 1
• Do not restrict access to interventions based on previous participation—fatigue and contributing factors can change over time. 1
• For patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), exercise can be harmful as it triggers postexertional malaise—these patients should be educated about pacing activity to not exceed their limited energy capacity. 6