What is the most common cause of chronic fatigue?

Most Common Causes of Chronic Fatigue

The most common causes of chronic fatigue in general medical practice are psychiatric disorders (particularly depression and anxiety), lifestyle factors (especially sleep disturbances), and medical conditions (including anemia, medications, and chronic diseases). 1, 2

Primary Diagnostic Categories

Psychiatric Disorders - The Leading Cause

• Depression and anxiety disorders represent the most frequently identified causes of chronic fatigue in primary care settings. 2
• Mood disorders, anxiety disorders, and somatoform disorders collectively account for the majority of chronic fatigue cases when systematically evaluated. 2
• Fatigue and depression commonly co-occur, though they are independent conditions with different temporal patterns—fatigue does not necessarily predict depression and vice versa. 3

Sleep Disturbances - Second Most Common

• Sleep disorders including insomnia, restless sleep, and disrupted sleep patterns are highly prevalent contributors to chronic fatigue. 4
• Sleep disturbances affect 30-75% of patients presenting with fatigue complaints. 3
• In children specifically, sleep disturbances are the single most common cause of fatigue, followed by psychiatric issues. 4

Medical Conditions - Third Category

• Anemia, infections, endocrine disorders (particularly thyroid dysfunction), and medication side effects constitute common medical causes. 1
• Chronic diseases including cancer, cardiac disease, and liver disease produce fatigue through multiple mechanisms. 5
• Laboratory abnormalities affect management in only 5% of patients with fatigue, indicating that most cases are not due to detectable organic disease. 1

Specific High-Risk Populations

Patients with Chronic Alcohol Use

• Hepatic encephalopathy and liver dysfunction are primary concerns, as chronic alcohol causes both liver failure and cardiac injury manifesting as fatigue. 5
• Thiamine deficiency occurs predominantly in alcohol use disorder and produces cerebral symptoms indistinguishable from other fatigue causes. 5
• Malnutrition from poor oral intake combined with alcohol use creates a synergistic effect exacerbating fatigue. 5

Cancer Patients

• Cancer-related fatigue affects 70-99% of patients when assessed by simple self-report. 3
• When strict diagnostic criteria are applied (requiring specific severity, duration, and functional impairment), prevalence drops to 15-30%. 3
• Contributing factors include the cancer itself, treatment effects, sleep disturbance, depression, pain, medication side effects, nutritional imbalance, and physical inactivity. 3

Critical Evaluation Approach

Initial Assessment Priorities

• Use a 0-10 numeric rating scale—scores of 4-10 indicate moderate to severe fatigue requiring focused evaluation, and scores ≥7 correlate with marked decreases in physical functioning. 5
• Assess onset pattern, duration, changes over time, and interference with daily function to differentiate between causes. 5

Nine Treatable Contributing Factors to Systematically Evaluate

• Pain, emotional distress, sleep disturbance, anemia, nutrition, activity level, alcohol/substance abuse, medication side effects (particularly sedation), and other comorbidities. 3
• Each factor requires specific assessment because fatigue rarely occurs from a single cause. 3

Laboratory Testing Limitations

• Initial laboratory results affect management in only 5% of cases. 1
• If initial laboratory studies are normal, repeat testing is generally not indicated. 1
• Focus testing on specific clinical suspicions rather than broad screening panels. 1

Common Diagnostic Pitfalls

• Never assume fatigue is solely due to one cause, especially in patients with chronic alcohol use or multiple comorbidities, as multiple organ systems may be simultaneously affected. 5
• Do not delay thiamine administration while awaiting laboratory results in patients with alcohol use disorder. 5
• Normal ammonia levels do not exclude hepatic encephalopathy—clinical presentation and treatment response may be the best diagnostic indicators. 5
• Patients often believe they have an organic medical disorder and resist psychiatric explanations, requiring flexible approach and rapport-building. 2

Management Framework

Universal Interventions

• Implement a structured plan for regular physical activity consisting of stretching and aerobic exercise such as walking—this is effective for all types of fatigue. 1
• Establish good sleep hygiene with consistent bedtime routines and appropriate sleep environments. 4
• Schedule regular follow-up visits rather than sporadic urgent appointments for effective long-term management. 1

Targeted Pharmacologic Interventions

• Selective serotonin reuptake inhibitors (fluoxetine, paroxetine, or sertraline) may improve energy in patients with depression. 1
• Caffeine and modafinil may be useful for episodic situations requiring alertness. 1
• Consider melatonin as an adjunctive strategy when appropriate for sleep disorders. 4

Behavioral Interventions

• Cognitive behavior therapy shows moderate improvement in fatigue levels, work and social adjustment, anxiety, and postexertional malaise. 6
• Short naps are proven performance enhancers. 1