Symptoms of Prednisone Withdrawal
Prednisone withdrawal manifests as a constellation of symptoms including weakness, fatigue, loss of appetite, weight loss, nausea, vomiting, diarrhea, abdominal pain, myalgia, arthralgia, and malaise, which can occur even when cortisol levels are adequate. 1
Clinical Presentation
Withdrawal symptoms fall into three distinct categories that require different management approaches:
True Adrenal Insufficiency Symptoms
- Weakness and profound fatigue are hallmark features when the hypothalamic-pituitary-adrenal (HPA) axis remains suppressed 1, 2
- Gastrointestinal symptoms including nausea, vomiting, diarrhea, and abdominal pain occur commonly 1
- Anorexia and weight loss develop as glucocorticoid levels fall below physiological needs 1
- Hypotension and volume depletion can occur in severe cases, potentially progressing to life-threatening adrenal crisis 3
Glucocorticoid Withdrawal Syndrome
- Myalgia and arthralgia are prominent features that occur despite adequate cortisol levels 1, 2
- Generalized malaise persists even when biochemical testing shows normal adrenal function 1, 4
- This syndrome results from tolerance to glucocorticoids and can last a median of 10 months (range 6-10 months) after withdrawal 4
- Symptoms can mimic adrenal insufficiency but occur with documented trough serum cortisol levels above 100 nmol/L 4
Neuropsychiatric Manifestations
- Depression occurs in a significant proportion of patients, with 18-40% experiencing moderate-severe depressive symptoms during withdrawal 5
- Sleep disturbances affect approximately 49% of patients withdrawing from glucocorticoids 5
- Fatigue is independently associated with poor quality of life during withdrawal 5
Critical Distinguishing Features
The major clinical challenge is differentiating between true adrenal insufficiency requiring replacement therapy, glucocorticoid withdrawal syndrome requiring temporary dose increase, and disease relapse. 1, 6
Monitoring During Withdrawal
- Laboratory tests should be performed frequently during drug withdrawal and for at least 3 months after termination 7, 1
- Serum aminotransferase levels (in autoimmune hepatitis) or disease-specific markers help distinguish withdrawal symptoms from disease flare 1
- HPA axis testing with ACTH stimulation should be performed if symptoms prevent treatment withdrawal 6
Risk Factors for Severe Withdrawal
- Doses exceeding 10 mg daily significantly increase the likelihood and severity of withdrawal symptoms 1
- Duration of therapy longer than 6 weeks substantially increases risk of HPA axis suppression 8
- Rapid tapering rather than gradual dose reduction precipitates more severe symptoms 2
Prevention Strategy
Gradual tapering is essential, with dose reductions of approximately 2.5 mg per month until the lowest effective dose is reached. 7, 1
- Corticosteroids should be withdrawn over a 6-week period after disease remission is achieved 7
- For patients on long-term therapy, the lowest dose possible (median 7.5 mg daily) should be used to prevent symptoms 1
- HPA axis suppression can persist for up to 12 months after discontinuation, requiring stress-dose coverage during intercurrent illness 2
Critical Pitfall to Avoid
Patients must be warned never to discontinue corticosteroids abruptly or without medical supervision, as this can precipitate life-threatening adrenal crisis. 2, 3 The FDA label explicitly states that patients should seek medical advice immediately if they develop acute illness including fever or signs of infection during or after withdrawal 2. Emergency identification cards warning about acute glucocorticoid replacement needs are essential for reducing morbidity and mortality 3.