What are the initial workup and treatment options for a patient presenting with generalized fatigue?

Initial Workup and Treatment for Generalized Fatigue

Begin by quantifying fatigue severity using a 0-10 numeric rating scale, where mild fatigue (scores 0-3) requires only education and periodic rescreening, while moderate to severe fatigue (scores 4-10) mandates a focused evaluation targeting treatable contributing factors. 1, 2

Severity Assessment and Initial Screening

• Use a standardized 0-10 numeric scale where 0 = no fatigue and 10 = worst fatigue imaginable 3, 1
• Mild fatigue (1-3): Provide education on general management strategies and rescreen at regular intervals 3, 1
• Moderate to severe fatigue (4-10): Proceed immediately to focused evaluation 1, 2
• Scores ≥7 typically indicate marked decrease in physical functioning and warrant urgent attention 1

Focused History for Moderate to Severe Fatigue

Document specific fatigue characteristics:

• Onset, pattern, duration, and changes over time 1, 2
• Associated or alleviating factors 1, 2
• Interference with normal functioning and daily activities 1
• Patient's self-assessment of potential causes 1

Screen for red flag symptoms that suggest serious underlying disease:

• Fever, drenching night sweats, unexplained weight loss 2
• Pain, pulmonary complaints 2
• Lymphadenopathy, hepatosplenomegaly, or skin manifestations 2
• For new immigrants or recent travelers: consider tropical diseases including malaria, tuberculosis, schistosomiasis, and dengue 2

Assessment of Treatable Contributing Factors

Systematically evaluate these common perpetuating factors:

• Pain: Assess and treat effectively as it commonly clusters with fatigue 1
• Emotional distress: Screen for depression and anxiety, which frequently co-occur with fatigue 1, 2
• Sleep disturbance: Evaluate sleep quality, quantity, and hygiene 1
• Medication side effects: Review all medications (including over-the-counter, herbal, vitamins, and supplements) and recent medication changes 3, 1
• Alcohol/substance use: Screen for misuse that may contribute to fatigue 1
• Comorbid conditions: Review status of non-cancer comorbidities and optimize their management 3

Laboratory Workup

For patients with moderate to severe fatigue (scores 4-10), order the following initial screening tests:

• Complete blood count with differential 2
• Comprehensive metabolic panel 2
• Thyroid-stimulating hormone 2
• Erythrocyte sedimentation rate 2
• C-reactive protein 2

Important caveat: Laboratory results affect management in only 5% of patients, and if initial results are normal, repeat testing is generally not indicated 4. Avoid "fishing expeditions" with additional testing if the initial workup is unrevealing 5.

Initial Treatment Approach

Implement these evidence-based interventions for all patients with fatigue, regardless of cause:

Nonpharmacologic Interventions (First-Line)

• Structured physical activity program: Begin with low-level activities that gradually increase over time, especially if the patient is significantly deconditioned 3, 2
• Sleep hygiene improvement: Address sleep quality, quantity, and hygiene issues 2
• Energy conservation strategies: Teach deliberately planned management of personal energy resources to prevent depletion 3
• Education and counseling: Provide information about fatigue's natural history and reassure that fatigue is not necessarily an indication of disease progression 3

Treatment of Identified Contributing Factors

• Depression/anxiety: Consider selective serotonin reuptake inhibitors (fluoxetine, paroxetine, or sertraline) to improve energy 4
• Pain management: Follow appropriate pain management guidelines 1
• Nutritional deficiencies: Address and correct as identified 2
• Medication adjustments: Delete or adjust doses of medications contributing to fatigue; alter dosage or dosing interval as needed 3

Pharmacologic Considerations

• Caffeine and modafinil: May be useful for episodic situations requiring alertness 4
• Short naps: Proven performance enhancers 4
• Antidepressants: May be tried on a pragmatic basis even in the absence of clear depression 6

Common Pitfalls to Avoid

• Do not overlook medication side effects as potential contributors to fatigue, including interactions between different medication classes (narcotics, antidepressants, antiemetics, antihistamines) 3, 1
• Do not convince fatigued patients to exercise aggressively: Begin with discussions and low-level activities, gradually increasing over time 3
• Do not order extensive repeat testing if initial laboratory workup is normal 4
• Recognize that fatigue rarely occurs in isolation and often clusters with other symptoms 1

Follow-Up Strategy

• Schedule regular follow-up visits rather than sporadic urgent appointments for effective long-term management 4
• Rescreen at regular intervals: Daily for inpatients, at subsequent routine visits for outpatients 3
• Monitor symptom evolution and adjust treatment accordingly 2
• Continue monitoring even after treatment as fatigue symptoms may persist 3