Does Fludrocortisone Cause Steroid-Induced Psychosis?
Fludrocortisone (Florinef) does not typically cause steroid-induced psychosis because it is a mineralocorticoid with minimal glucocorticoid activity, and psychiatric side effects are specifically associated with glucocorticoid receptor activation, not mineralocorticoid effects.
Understanding the Mechanism
The key distinction lies in the pharmacological properties of fludrocortisone:
Fludrocortisone is primarily a mineralocorticoid that works by causing sodium retention, water expansion, and direct effects on blood vessels—not through glucocorticoid receptor-mediated psychiatric effects 1
Steroid-induced psychosis occurs with glucocorticoids (like prednisone, hydrocortisone, dexamethasone) at doses equivalent to prednisone ≥1 mg/kg or more, manifesting primarily as mood disorders (93%) rather than frank psychosis 2
The incidence of severe psychiatric reactions is approximately 5% with glucocorticoid therapy, typically presenting as affective and/or psychotic symptoms early in treatment 3
Clinical Evidence on Glucocorticoid-Induced Psychosis
When psychiatric side effects do occur with corticosteroids, they follow a predictable pattern:
Depression and mania are most frequent, followed by psychosis and delirium, particularly in patients treated with systemic glucocorticoids 4
High-dose hydrocortisone (400 mg/24 hours) used for adrenal crisis has been documented to cause acute psychosis with hallucinations and delusions 5
Even single doses of glucocorticoids (such as 10 mg dexamethasone epidurally) can trigger psychosis in susceptible individuals 6
Psychiatric symptoms typically manifest within days of starting glucocorticoid therapy and resolve within 7-17 days after discontinuation or dose reduction 6, 3
Risk Factors for Glucocorticoid-Induced Psychosis
The established risk factors apply to glucocorticoids, not mineralocorticoids:
Female sex, high doses, and systemic lupus erythematosus are documented risk factors for steroid-induced psychiatric syndromes 3
Prior corticosteroid-induced psychiatric side effects increase risk in females, though elderly patients and those with previous psychiatric diagnoses are not at increased risk 4
The dose is the most important risk factor—prescribing the lowest effective dose is the primary preventive measure 7
Fludrocortisone-Specific Considerations
Fludrocortisone's side effect profile is distinctly different:
Common adverse effects include hypokalemia, hypertension, and fluid retention—not psychiatric symptoms 1
Monitoring focuses on blood pressure (supine and standing), serum electrolytes (sodium and potassium), and signs of fluid overload—not mental status changes 8, 1
The medication must be taken daily (not alternate-day) at doses of 0.05-0.2 mg for most patients, with careful titration based on blood pressure and electrolytes, not psychiatric symptoms 8
Critical Clinical Pitfall
Do not confuse fludrocortisone with glucocorticoids when assessing psychiatric risk. If a patient on fludrocortisone develops psychosis, investigate other causes including:
- Concurrent glucocorticoid therapy (hydrocortisone is often co-prescribed for adrenal insufficiency) 2
- Underlying medical conditions (infections, metabolic disturbances, adrenal crisis itself) 2
- Other medications or substance use
- Primary psychiatric disorders
When Psychiatric Symptoms Do Occur with Corticosteroids
If a patient requires glucocorticoid therapy and develops psychiatric symptoms:
Treatment involves stopping or tapering the glucocorticoid if possible, and targeting specific psychiatric symptoms with haloperidol or atypical antipsychotics 2, 5
Tricyclic antidepressants do not appear useful for steroid-induced psychiatric syndromes 3
Most patients recover within several weeks of symptom onset with appropriate management 3
Consider budesonide 9 mg/day plus azathioprine instead of systemic glucocorticoids in patients at high risk for psychiatric complications (those with poorly controlled diabetes, osteoporosis, or pre-existing psychosis) 2