What are the long-term effects of prednisone (corticosteroid) therapy?

Long-Term Effects of Prednisone Therapy

Prednisone therapy causes significant adverse effects on multiple organ systems with risks increasing with higher doses (≥7.5 mg daily) and longer duration of treatment (>3 months), requiring preventive measures from the outset of therapy. 1

Major Long-Term Effects by System

Musculoskeletal System

• Osteoporosis and Fracture Risk
  • Fracture risk increases within 3 months of starting therapy 1
  • Higher doses (≥7.5 mg daily) significantly increase fracture risk 1
  • Suppresses multiple indices of bone formation even at low doses (5 mg/day) 2
  • Vertebral compression fractures occur in 27% of patients on long-term therapy 1
  • Prevention requires:
    • Calcium (800-1000 mg daily) and vitamin D (800 IU daily) supplementation 1
    • Baseline bone mineral density testing within 1 month of starting therapy 1
    • Bisphosphonate therapy for high-risk patients 1

Endocrine System

• Adrenal Suppression

  • Occurs in approximately 50% of patients after withdrawal of medium/high-dose therapy 1
  • Requires gradual tapering when discontinuing therapy to prevent withdrawal syndrome 1, 3
  • Symptoms include weakness, fatigue, nausea, vomiting, and pain 1

• Metabolic Disturbances

  • Brittle diabetes in 20% of patients requiring treatment withdrawal 1
  • Hyperglycemia requiring monitoring and potential adjustment of antidiabetic medications 3
  • Hypokalemia, especially when used with potassium-depleting agents 3

Cardiovascular System

• Hypertension requiring regular monitoring 1, 3
• Increased risk of atherosclerosis 1
• Aortic aneurysm development risk increases with:
  • Higher doses (≥7.5 mg daily) 1
  • Treatment exceeding 3 months 1
  • Cumulative prednisone dose 1

Dermatologic Effects

• Skin changes in 80% of patients after 2 years, including: 1

  • Skin thinning
  • Easy bruising
  • Striae
  • Acne
  • Facial hirsutism

• Cushingoid appearance in 80% of patients after 2 years 1

  • Facial rounding
  • Weight gain
  • Central obesity

Infectious Complications

• Increased risk of serious infections (hazard ratio 1.57) 1
• Increased mortality risk (hazard ratio 2.14) 1
• Reactivation of latent infections like tuberculosis 3
• Increased susceptibility to varicella and measles with potentially fatal outcomes 3

Ophthalmologic Effects

• Posterior subcapsular cataracts with prolonged use 1
• Glaucoma with elevated intraocular pressure requiring monitoring after 6 weeks of therapy 3

Neuropsychiatric Effects

• Mood disturbances ranging from euphoria to severe depression 3
• Insomnia (most common short-term side effect) 4
• Personality changes and potential psychotic manifestations 3

Risk Factors and Prevention

Risk Factors for Complications

• Higher doses (≥7.5 mg daily) 1, 5
• Longer duration of therapy (>3 months) 1
• Pre-existing conditions (diabetes, osteoporosis, glaucoma, hypertension) 6
• Age ≥40 years (higher risk for osteoporosis) 1

Preventive Measures

1. Use lowest effective dose for shortest duration possible 1
2. Regular monitoring of:
   • Blood pressure
   • Blood glucose
   • Potassium levels
   • Bone mineral density
   • Eye examinations
3. Prophylactic medications:
   • Calcium and vitamin D for all patients 1
   • Bisphosphonates for high fracture risk 1
   • Consider prophylactic co-trimoxazole for infection prevention in high-risk patients 1
4. Complete immunizations before starting therapy 1
5. Gradual tapering when discontinuing to prevent adrenal insufficiency 1, 3

Special Considerations

Dosing Strategies

• Alternate-day therapy may reduce adverse effects by allowing HPA axis recovery on off days 3
• Morning administration (before 9 AM) minimizes adrenal suppression 3
• Tapering schedules should be individualized based on disease activity and risk factors 3

High-Risk Situations

• Pregnancy: Effective birth control recommended; some preventive medications (e.g., bisphosphonates) have fetal risks 1
• Surgery: May require stress-dose steroids due to adrenal suppression 3
• Infection: Increased vigilance needed; may mask signs of infection 3

Conclusion

The decision to use long-term prednisone therapy requires careful consideration of benefits versus risks. Evidence shows that even low doses (5 mg/day) can cause significant adverse effects over time 2, 5. When long-term therapy is necessary, implementing preventive strategies from the outset and using the lowest effective dose for the shortest duration is essential to minimize these risks 1.