Does prednisone (corticosteroid) cause fatigue in patients with moderate to severe ulcerative colitis?

Does Prednisone Cause Fatigue?

Yes, prednisone commonly causes fatigue as part of its adverse effect profile, with approximately 50% of patients experiencing short-term corticosteroid-related adverse events including sleep disturbance and mood changes, both of which contribute to fatigue. 1, 2

Understanding Corticosteroid-Related Fatigue

The fatigue associated with prednisone occurs through multiple mechanisms:

• Sleep disturbance is a well-documented adverse effect that directly contributes to daytime fatigue 1
• Mood changes including irritability and depression can manifest as or worsen fatigue 1
• Metabolic effects such as glucose intolerance may contribute to energy fluctuations 1

Clinical Context in Ulcerative Colitis

When treating moderate to severe ulcerative colitis with prednisone:

• The standard dose is 40-60 mg daily with a 6-8 week taper 1, 3
• Single daily dosing causes less adrenal suppression than split-dosing, which may reduce some fatigue-related effects 1
• The median total duration of therapy in patients achieving remission is approximately 4 months, with a median total dose just above 3 grams 4

Important Clinical Considerations

Adrenal suppression becomes a concern with prolonged use:

• Gradual tapering over 6-8 weeks is essential to minimize relapse risk and allow adrenal recovery 1
• Abrupt discontinuation can worsen fatigue through adrenal insufficiency 1

The underlying disease itself contributes to fatigue:

• Active ulcerative colitis causes systemic inflammation that produces fatigue independent of medication effects 5
• As prednisone induces remission, disease-related fatigue may improve even while medication-related fatigue persists 4

Managing Fatigue During Treatment

Optimize dosing strategy:

• Use single daily dosing rather than split doses to reduce adrenal suppression 1
• Consider topically-acting corticosteroids (budesonide MMX 9 mg/day or beclomethasone dipropionate 5 mg/day) for patients wishing to avoid systemic effects, though these may be less effective for moderate-severe disease 1

Monitor for treatment escalation needs:

• Patients requiring two or more courses of corticosteroids in the past year should be escalated to steroid-sparing therapies (thiopurines, anti-TNF therapy, vedolizumab, or tofacitinib) 1
• Corticosteroids should never be used for long-term maintenance therapy due to cumulative adverse effects 3

Common Pitfall to Avoid

Do not attribute all fatigue to prednisone without considering:

• Active disease inflammation as a primary cause of fatigue 5
• Anemia (hemoglobin <10.5 g/dL is part of the severe UC criteria) 5
• Concurrent infections, particularly Clostridium difficile, which must be excluded before attributing symptoms to medication 5