Prednisone Effects and Side Effects

Direct Answer

Prednisone causes dose-dependent and duration-dependent side effects affecting nearly every organ system, with the most serious complications—including osteoporosis, infections, metabolic disturbances, and neuropsychiatric effects—occurring primarily at doses >10 mg daily for prolonged periods. 1

Therapeutic Effects

Prednisone provides potent anti-inflammatory and immunosuppressive effects that are beneficial for treating various inflammatory and autoimmune conditions. 2 The clinical benefits typically outweigh risks when used appropriately at the lowest effective dose for the shortest duration. 1, 2

Short-Term Side Effects (First Few Weeks to 6 Weeks)

Common Early Effects

Weight gain and fluid retention occur within the first few weeks and are among the most frequently reported patient concerns 1, 3
Increased appetite leading to additional weight gain 1, 3
Insomnia, restlessness, and nervousness affect over 30% of patients 1, 3
Facial rounding (moon face) can begin developing even during short-term use 1, 3
Mood disturbances ranging from euphoria and hypomania to depression, anxiety, and emotional instability 1, 3
Gastric irritation and increased risk of peptic ulcer formation 3, 4
Hypertension can develop or worsen quickly 3, 4

Critical Threshold

Duration of treatment longer than 6 weeks significantly increases the risk of adverse effects. 3 Most short-term side effects are dose-dependent, with higher doses causing more frequent and severe reactions. 3

Long-Term Side Effects (>6 Weeks, Especially >10 mg Daily)

Musculoskeletal Complications (Most Serious)

Osteoporosis and increased fracture risk are among the most serious complications, with vertebral compression fractures occurring in up to 27% of patients 1, 3
Aseptic necrosis of femoral and humeral heads can develop even at moderate doses 1, 3
Myopathy affecting diaphragmatic and intercostal muscles 3, 4
Even doses as low as 5 mg daily can suppress bone formation markers in postmenopausal women 5

Metabolic and Endocrine Effects

Hyperglycemia and worsening of diabetes are common, particularly with prednisone, requiring blood glucose monitoring 1, 3
Redistribution of body fat with truncal obesity, moon facies, and buffalo hump occurs in 80% of patients after two years 1, 3
HPA axis suppression with potential for adrenocortical insufficiency that may persist up to 12 months after discontinuation 4
Dyslipidemia increasing cardiovascular disease risk 3

Ophthalmologic Effects

Posterior subcapsular cataracts develop with prolonged use 1, 3, 4
Increased intraocular pressure and glaucoma can occur 1, 3, 4
Regular eye examinations are essential for long-term users 1, 3

Neuropsychiatric Effects

Severe mood disturbances including depression, psychosis, delirium, and cognitive impairment 1, 4
Memory deficits, impaired concentration, and personality changes 4
Psychiatric symptoms occur in over 30% of patients, with severe effects mainly at doses >20 mg/day 1, 6

Dermatologic Effects

Skin atrophy, thinning, and fragility 1, 3, 4
Impaired wound healing 4
Ecchymoses, petechiae, and striae 4

Infectious Complications

Increased risk of both opportunistic and non-opportunistic infections, including pneumonia, skin infections, and sepsis 1, 3, 4
Reactivation of latent tuberculosis 4
Hepatitis B virus reactivation in carriers 4
Varicella and measles can have serious or fatal courses in non-immune patients 4
Exacerbation of systemic fungal infections 4
Activation of latent amebiasis and Strongyloides 4
Infections can be masked by corticosteroid effects 4

Cardiovascular Effects

Hypertension or aggravation of existing hypertension 1, 4
Salt and water retention with increased potassium excretion 4
Left ventricular free wall rupture after recent myocardial infarction (use with great caution) 4
Thromboembolism and thrombophlebitis 4

Gastrointestinal Effects

Peptic ulcer with possible perforation and hemorrhage 1, 4
Perforation of small and large intestine, particularly in inflammatory bowel disease 4
Pancreatitis 4

Dose-Dependent Risk Profile

Critical Dose Thresholds

Doses >20 mg/day for >18 months: Severe adverse effects occur in approximately 15% of patients 1, 3, 6
Doses >10 mg daily for prolonged periods: Significantly increase risk of serious complications 1, 3
Doses 5-10 mg daily: Still associated with increased adverse events (OR 4.5) compared to no prednisone 7
Doses >10-15 mg daily: Most strongly correlated with adverse events (OR 32.3) 7

Even low doses (5 mg daily) can suppress bone formation and may have adverse effects on bone mass. 5

Critical Monitoring Requirements

Baseline Screening

Screen for hepatitis B infection before initiating immunosuppressive treatment 4
Rule out latent tuberculosis or provide chemoprophylaxis during prolonged therapy 4
Rule out latent amebiasis in patients who have spent time in the tropics 4

Ongoing Monitoring

Blood pressure and blood glucose monitoring regularly 1, 3
Bone density testing (baseline and annual) for long-term therapy 1, 3
Regular eye examinations for cataracts and glaucoma 1, 3
Monitor for signs of infection and consider dose reduction if infections develop 4
Psychiatric evaluation between 2-4 weeks for mood instability, sleep disturbances, agitation, and psychotic symptoms 6

Prevention Strategies

Mandatory Prophylaxis

Calcium and vitamin D supplementation for all patients receiving corticosteroids to prevent osteoporosis 1, 3
Pneumocystis jirovecii pneumonia prophylaxis for patients taking ≥20 mg prednisone for ≥4 weeks 1, 3

Exposure Prophylaxis

Varicella zoster immune globulin if exposed to varicella; consider antiviral agents if varicella develops 4
Immunoglobulin if exposed to measles 4
Update all vaccines before starting immunosuppressive therapy; avoid live vaccines once on treatment 3

Dose Minimization Strategies

Use the lowest effective dose for the shortest duration possible 3
Consider alternate-day therapy when appropriate to reduce adrenal suppression 3
Consider steroid-sparing agents when long-term therapy is anticipated 3
In non-cirrhotic patients with specific conditions, consider budesonide instead of systemic prednisolone (significantly fewer psychiatric side effects) 6

Special Population Considerations

Pediatric Patients

Growth suppression is a major concern, occurring even at low systemic doses without laboratory evidence of HPA axis suppression 1, 3
Higher risk for HPA axis suppression with topical steroids due to higher skin surface/body mass ratio 3

Elderly Patients

Require more careful monitoring and often lower doses due to increased risk of complications 1, 3

High-Risk Patients

Patients with diabetes, chronic liver disease, or chronic kidney disease have increased risk of complications and require close monitoring 3
Patients with bipolar disorder or history of steroid-induced psychosis should avoid prednisone/prednisolone entirely if possible 6

Pregnancy Considerations

Low-dose corticosteroids (≤10 mg daily) have not been proven to cause fetal wastage, prematurity, or congenital malformations 8

Common Pitfalls to Avoid

Withdrawal Management

Never abruptly discontinue prednisone after prolonged use; adrenocortical insufficiency may result from too rapid withdrawal 4
HPA axis suppression may persist up to 12 months after discontinuation; reinstitute hormone therapy during stress situations 4
Gradual dose reduction minimizes withdrawal complications 4

Infection Management

Do not underestimate infection risk; corticosteroid-associated infections can be mild but can be severe and at times fatal 4
Signs of infection may be masked by corticosteroid effects 4
Consider prednisone withdrawal or dosage reduction when infections develop 4

Quality of Life Impact

Do not underestimate the impact of sleep disturbances and mood changes on quality of life 3
Insomnia was the chief side effect in short-term treatment in clinical studies 2

Thyroid Considerations

Metabolic clearance of corticosteroids is decreased in hypothyroid patients and increased in hyperthyroid patients; adjust dosage accordingly 4

Stress Dosing

Increased dosage is indicated in patients on corticosteroid therapy subjected to unusual stress before, during, and after the stressful situation 4

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