What percentage of patients experience fatigue as a direct adverse effect of prednisone?

Fatigue as a Direct Adverse Effect of Prednisone

Approximately 2-9% of patients experience fatigue as a direct adverse effect of prednisone, though this varies significantly based on dosage, duration, and individual factors. 1

Mechanisms of Prednisone-Related Fatigue

Prednisone can cause fatigue through several mechanisms:

• Direct effects: Corticosteroids can directly cause fatigue in some patients
• Withdrawal effects: Adrenal suppression occurs in approximately 50% of patients after withdrawal of medium/high-dose therapy, presenting with weakness and fatigue 2
• Steroid withdrawal syndrome: Can present with fatigue and weakness when tapering corticosteroids 2
• Secondary effects: Prednisone can cause conditions that lead to fatigue:
  • Depression (as seen in Case 1 from 3)
  • Steroid-induced myopathy (as seen in Case 2 from 3)
  • Hyperglycemia (as seen in Case 3 from 3)

Incidence Rates by Context

The incidence of fatigue varies significantly depending on the clinical context:

1. Cancer treatment context:

   • In metastatic castration-resistant prostate cancer patients receiving abiraterone plus prednisone, fatigue was reported in 8-9% of patients (grade 3 severity) 1
   • In patients receiving mitoxantrone plus prednisone, fatigue was reported in 3% of patients (grade 3-5 severity) 1
   • In patients receiving cabazitaxel plus prednisone, fatigue was reported in 5% of patients (grade 3-5 severity) 1

2. Rheumatoid arthritis context:

   • Delayed-release prednisone actually improved fatigue compared to placebo in RA patients 4

3. Elderly patients:

   • Higher risk of fatigue as an adverse drug reaction, particularly when combined with multiple medications 5

Risk Factors for Prednisone-Related Fatigue

Several factors increase the risk of experiencing fatigue with prednisone:

• Higher doses of prednisone 2
• Longer treatment duration 2
• Polypharmacy (taking multiple medications) 5
• Older age 5
• Pre-existing conditions such as diabetes 3
• Rapid tapering of prednisone 2

Clinical Pearls and Pitfalls

• Paradoxical effects: While prednisone is sometimes used to treat fatigue in certain conditions (like cancer-related fatigue), it can also cause fatigue as an adverse effect 1, 6

• Monitoring: Regular assessment of fatigue and other symptoms is essential during prednisone therapy 2

• Differential diagnosis: When fatigue develops during prednisone therapy, consider:

  • Steroid-induced depression
  • Steroid-induced myopathy
  • Hyperglycemia
  • Electrolyte disturbances
  • Adrenal suppression 3

• Pitfall to avoid: Increasing the prednisone dose when fatigue develops may worsen the problem if the fatigue is a direct adverse effect of the medication 3

Management of Prednisone-Related Fatigue

If fatigue develops as an adverse effect:

1. Consider dose reduction if clinically appropriate
2. Rule out secondary causes (check blood glucose, electrolytes, screen for depression)
3. Treat specific mechanisms (e.g., antidepressants for depression, insulin for hyperglycemia)
4. Consider alternative formulations (e.g., switching from betamethasone to prednisolone may help in cases of steroid myopathy) 3
5. Ensure adequate calcium and vitamin D supplementation 2

The evidence regarding prednisone and fatigue is complex, as prednisone can both cause and alleviate fatigue depending on the clinical context. The Cochrane review from 2023 concluded there is insufficient evidence to support or refute the use of systemic corticosteroids for cancer-related fatigue 6.