What are the long-term effects of taking prednisone (corticosteroid) for extended periods?

Long-Term Effects of Prednisone

Prolonged prednisone therapy, especially at doses >10 mg daily, is frequently associated with well-known drug toxicities and should be avoided, with treatment courses ideally limited to 6-8 weeks unless absolutely necessary. 1, 2

Critical Time and Dose Thresholds

The risk profile for prednisone-related complications follows clear dose-duration relationships that should guide clinical decision-making:

• Courses longer than 6 weeks are associated with a large risk of harm and likelihood of adverse events, including hypertension, hyperglycemia, sleep and mood disturbances, gastric irritation, glaucoma, myopathy, and osteoporosis 2, 1
• Doses exceeding 10 mg daily for more than 18 months significantly increase the risk of severe complications, with severe adverse effects occurring in approximately 15% of patients 3, 4
• Treatment duration >2 weeks is when most adverse effects begin to manifest, with fluid retention and insomnia being the earliest symptoms 5

Major Long-Term Complications by System

Musculoskeletal Effects

Osteoporosis and fracture risk represent the most serious long-term complication, particularly in postmenopausal women:

• Vertebral compression fractures occur in up to 27% of patients, sometimes requiring treatment withdrawal 3
• Corticosteroids decrease bone formation and increase bone resorption through effects on calcium regulation and inhibition of osteoblast function 6
• Fractures occurred in 21 patients on chronic low-dose prednisone versus 8 matched controls in one cohort study 4
• Aseptic necrosis of femoral and humeral heads can develop even at moderate doses 3, 7
• Myopathy affecting diaphragmatic and intercostal muscles may occur, potentially complicating assessment of therapeutic efficacy 3

Metabolic and Endocrine Effects

Weight gain, glucose intolerance, and adrenal suppression are nearly universal with prolonged use:

• Redistribution of body fat with truncal obesity, moon facies, and buffalo hump occurs in 80% of patients after two years of therapy 3
• Cosmetic changes include facial rounding, hirsutism, alopecia, dorsal hump, and striae 1
• Glucose intolerance/diabetes develops commonly, requiring blood glucose monitoring 1, 3
• Drug-induced secondary adrenocortical insufficiency may persist for up to 12 months after discontinuation following large doses for prolonged periods 6
• Dyslipidemia occurs with long-term use, increasing cardiovascular disease risk 3

Ophthalmologic Complications

Regular eye examinations are mandatory for patients on long-term therapy:

• Posterior subcapsular cataracts develop with prolonged use 1, 3, 7
• Cataracts occurred in 17 patients on chronic prednisone versus 5 controls in one study 4
• Increased intraocular pressure and glaucoma can occur 1, 3
• If steroid therapy is continued for more than 6 weeks, intraocular pressure should be monitored 6

Gastrointestinal Effects

GI complications require careful monitoring, though peritoneal signs may be masked:

• GI bleed or ulcer occurred in 11 patients on chronic prednisone versus 4 controls 4
• Signs of peritoneal irritation following gastrointestinal perforation may be minimal or absent in patients receiving corticosteroids 6
• Steroids should be used with caution in active or latent peptic ulcers, diverticulitis, and fresh intestinal anastomoses 6

Infectious Disease Risk

Immunosuppression increases both opportunistic and non-opportunistic infection risk:

• Serious infections occurred in 14 patients on chronic prednisone versus 4 controls 4
• Consider Pneumocystis jirovecii pneumonia prophylaxis for patients taking ≥20 mg prednisone for ≥4 weeks 3
• Increased risk of pneumonia, skin infections, and sepsis 3

Neuropsychiatric Effects

Mood disturbances are common and can be severe:

• Psychiatric derangements range from euphoria, insomnia, mood swings, and personality changes to severe depression and frank psychotic manifestations 6, 7
• Emotional instability, psychosis, depression, and anxiety can occur 1
• Sleep disturbances occur in >30% of patients 3
• Insomnia was the chief side effect in patients receiving short-term treatment 5

Cardiovascular Effects

• Hypertension can develop or worsen, with sodium retention causing resultant edema and potassium loss 1, 6
• Agents should be used with caution in patients with congestive heart failure or hypertension 6
• Observational studies suggest long-term use of higher doses (≥5 mg prednisone) in rheumatoid arthritis patients is associated with higher cardiovascular event risk 1

Dose-Response Relationship for Adverse Events

A clear dose-dependent pattern exists for serious complications:

• Average prednisone dose >10 to ≤15 mg/day showed the strongest correlation with adverse events (Odds Ratio = 32.3) 4
• Average prednisone 5-10 mg/day had an Odds Ratio of 4.5 for adverse events 4
• Kaplan-Meier survival curves demonstrate a dose-response relationship between prednisone and adverse event occurrence 4
• Even doses <5 mg/day over long periods showed primarily bruising and skin-thinning, with lower levels of hypertension, diabetes, and cataracts 8

Special Population Considerations

Pediatric Patients

Growth suppression is a critical concern in children:

• Growth and development of infants and children on prolonged corticosteroid therapy should be carefully observed 6
• In children with autoimmune hepatitis, the goals of therapy are to eventually be glucocorticoid-free and to prevent the multiple long-term complications of glucocorticoids 1
• Growth retardation is a potential concern in pediatric patients using corticosteroids long-term 3

Pregnancy

Prednisone and prednisolone can be used in pregnancy but require careful dose management:

• Prednisone and prednisolone are not associated with increased rate of major birth defects 1
• Due to dose-related potential risks, use in pregnancy warrants careful consideration 1
• Adverse effects during pregnancy at higher doses may include pregnancy-associated osteoporosis, gestational diabetes, serious maternal infections, and preterm birth 1
• Daily doses ≤5 mg are associated with low risk 1

Risk Mitigation Strategies

Bone Health Protection

All patients anticipated to receive ≥5 mg prednisone for ≥3 months require bone protection:

• Calcium and vitamin D supplementation should be initiated 6
• Bisphosphonate therapy (e.g., alendronate, risedronate) should be initiated if bone mineral density is below normal 6
• Weight-bearing exercise program for 30-60 minutes daily should be encouraged 6
• Baseline and annual bone mineral density testing for patients on long-term therapy 3
• Lifestyle modification including cigarette smoking cessation and limitation of alcohol consumption 6

Monitoring Requirements

Systematic monitoring is essential to detect complications early:

• Regular monitoring of blood pressure and blood glucose, even during short courses 3
• Regular eye examinations for cataracts and glaucoma 3
• Weight monitoring to detect rapid fluid retention 3
• If steroid therapy continues >6 weeks, intraocular pressure should be monitored 6

Steroid-Sparing Approaches

Alternative immunosuppressive agents should be considered early:

• For autoimmune hepatitis, prednisone may be discontinued completely after achieving remission, leaving the patient on only azathioprine or alternative glucocorticoid-sparing drugs 1
• Consider steroid-sparing agents when long-term therapy is anticipated 3
• For IgG4-related disease and IRC, conventional corticosteroid-sparing agents include azathioprine, 6-mercaptopurine, mycophenolate mofetil, cyclosporine A, tacrolimus, or periodic rituximab 1

Critical Pitfalls to Avoid

• Do not continue corticosteroids beyond 6-8 weeks without reassessing the need for alternative immunosuppressive therapy 2
• Do not use arbitrary time intervals between courses—decisions should be based on disease response, alternative treatment options, and cumulative steroid exposure 2
• Do not abruptly discontinue corticosteroids without medical supervision, as prolonged use causes adrenal insufficiency and makes patients dependent 6
• Do not underestimate the impact of sleep disturbances and mood changes on quality of life 3
• Do not prescribe budesonide in cirrhosis, as it cannot reach the liver with portal hypertensive shunts 1

Disease-Specific Duration Limits

Specific guidelines exist for maximum treatment duration in certain conditions:

• For Immune Thrombocytopenia (ITP), strongly recommend against prolonged courses (>6 weeks) and favor short courses (≤6 weeks) 2
• For Inflammatory Bowel Disease (Crohn's Disease), offer systemic corticosteroids for no longer than 8 weeks 2
• Repeated courses of steroids should be avoided unless futility of other effective therapies has been established 2