Fatigue is a common and nonspecific symptom with a broad range of etiologies including acute or chronic medical conditions, psychological conditions, medication related effects, substance use.

• 1/3 of primary care visits are centered around fatigue

History

• First ask what your patient means by fatigue; here are some common responses:
  • Anhedonia, abulia (lack of motivation)
  • difficulty initiating activities
  • subjective sense of weakness
  • difficulty with concentration, memory
  • problems with initiating or sustaining sleep
  • dyspnea on exertion; decreased exercise tolerance
• UpToDate has a great table with causes of subacute and chronic fatigue: https://www.uptodate.com/contents/image?imageKey=PC%2F116315&topicKey=PC%2F2783&search=fatigue&rank=1~150&source=see_link
• Other questions to ask in history: 
  • ask how long has the patient has been feeling fatigued
  • ask about functional limitations (e.g. are they able to carry out their tasks at work)
  • ***Ask about what a typical day looks like*** (what time do you wake up, what are you doing during the day)
  • screen for depression with PHQ2 -> if positive -> PHQ9
  • screen for anxiety
  • ask about sleep (what time do you go to bed, what do you do before going to bed, how long does it take to fall asleep, how often do you wake up at night, what time do you wake up?)
  • screen for OSA with STOP-BANG (https://www.mdcalc.com/stop-bang-score-obstructive-sleep-apnea)
  • Screen for drug and alcohol use (e.g. AUDIT-C or Binge drinking screening question)
  • Supplements (e.g. St. John’s wart)

After a careful physical exam (see UpToDate table above for key physical exam findings), here are some initial screening labs to consider:

• CBC
• CMP
• TSH
• Vitamin D – can use supplementation as a placebo effect
• Vitamin B12 – B12 deficiency can be caused by metformin and PPI use; consider MMA if B12 in ~300 range, supplement if <200
• Appropriate cancer screening interventions based upon the patient’s age and sex should be updated as necessary to exclude common occult malignancies as a potential cause for fatigue.

Chronic fatigue syndrome (CFS)

• High prevalence with depression, trauma, fibromyalgia, POTS
• Underlying pathophysiology is unclear but may be associated with epigenetic changes caused by trauma; high risk of chronic medical conditions in patients with early childhood trauma
• Diagnosis of exclusion; diagnostic criteria from Institute of Medicine of the National Academies. Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an illness. Report Brief, February 2015:

CFS Diagnosis requires that the patient have the following three symptoms:

1. A substantial reduction or impairment in the ability to engage in pre-illness levels of occupational, educational, social, or personal activities that persists for more than six months and is accompanied by fatigue, which is often profound, is of new or definite onset (not lifelong), is not the result of ongoing excessive exertion, and is not substantially alleviated by rest.
2. Post-exertional malaise – Worsening of a patient’s symptoms and function after exposure to physical or cognitive stressors that were normally tolerated before disease onset.
3. Unrefreshing sleep.

At least one of the two following manifestations is also required:

1. Cognitive impairment – Problems with thinking or executive function exacerbated by exertion, effort, or stress or time pressure.
2. Orthostatic intolerance – Worsening of symptoms upon assuming and maintaining upright posture. Symptoms are improved, although not necessarily abolished, by lying back down or elevating the feet.

Therapies:

• Counseling: Tell patients that fatigue is rarely one thing. Usually combination of multiple factors – anxiety, sleep, anemia, etc.
• Counseling on substance use:
  • Focus on the long-term consequences (e.g. “While alcohol may help you sleep at night, over time, use of substances will not get you quality sleep.”)
  • It may take > 1 month off substance until patient notices a difference.
• Exercise:
  • do not have to go to the gym and work out 1-2 hours in order to get exercise
  • goal is increase physical activity
  • Set a smart goal
  • Ask what is a realistic amount of time you can walk each day? E.g. start 5 min, add 1 min a week, by end of a year, will be working out 60 min

• A trial of antidepressant drugs should be offered to patients with depressive symptoms:
  • SSRI
    • Fluoxetine – most stimulating; most weight neutral; starting dose 10mg daily
    • Vortioxetine
    • Generally, better to dose SSRIs in the morning to avoid causing insomnia
  • SNRI
    • Venlafaxine – starting dose 37.5 mg daily
    • Duloxetine – starting dose 20 mg daily; better if targeting pain
    • Desvenlafaxine – 50-100 mg; doesn’t have as many drug-drug interactions
    • Milnacipran – FDA approved for fibromyalgia
    • Levomilnacipran
  •  Bupropion
    • Has more stimulating effect
    • Can help with weight loss
    • great for smoker with fatigue
    • SR formulation is cheaper; BID dosing (don’t take 2^nd dose at bedtime; better to take at breakfast and before dinner); start at 100 mg daily (150 mg approved for smoking cessation)
    • XL is once a day dosing; has fewest side-effects; doses: 150, 300, 450mg
    • Side-effects:
      • Risk of seizures is relatively low, but still avoid in pt with seizure disorder
      • Avoid in pt with eating disorder
• CBT may be useful in some patients with idiopathic chronic fatigue. It typically involves a series of one-hour sessions designed to alter beliefs and behaviors that may delay recovery. It is also offered online.
• Follow-up: Have the patient return to clinic within first 1-2 months to assess progress

Summarized by Dr. Eric Wei based on a presentation from Dr. Gregory Brown

Excellent visual recap on insomnia by Dr. Wei. Adapted from a lecture by Dr. Spector

Another excellent infographic by Dr. Eric Wei, adapted from morning report by Dr. Metz.

Weight loss medications