What is the appropriate treatment for acute psychosis caused by glucocorticoid therapy?

Treatment of Acute Steroid-Induced Psychosis

Immediate Management Strategy

The primary treatment for acute steroid-induced psychosis is dose reduction or discontinuation of the corticosteroid combined with antipsychotic medication, with haloperidol or risperidone being the most effective agents based on clinical evidence. 1

Step 1: Corticosteroid Management

• Reduce the steroid dose immediately if the underlying condition permits, as dosage reduction typically results in clinical recovery and is the most critical intervention 2
• For patients requiring continued high-dose steroids (such as those with acute severe autoimmune hepatitis, adrenal crisis, or active lupus), dose reduction should occur as rapidly as the underlying disease allows 3, 4
• Consider dose adjustments for patients with pre-existing risk factors including diabetes (initial dose 20-40 mg daily reduced to 20-30 mg), psychosis history (20-30 mg daily), or osteoporosis, as these comorbidities increase vulnerability to neuropsychiatric complications 3

Step 2: Antipsychotic Selection

Haloperidol is the most commonly prescribed and evidence-supported antipsychotic for steroid-induced psychosis, used successfully in multiple case series 1, 4

• Risperidone is the preferred alternative, particularly in adolescents and when prophylaxis is needed during continued steroid therapy 5, 1
• Risperidone dosing for acute psychosis in adults typically ranges from 1-6 mg/day, with efficacy demonstrated at 4-6 mg/day for acute psychotic symptoms 6
• Treatment duration is typically 3-7 days until psychotic symptoms resolve following steroid dose reduction 4, 1

Step 3: Clinical Monitoring

• Evaluate for life-threatening behaviors immediately, as steroid psychosis can present with severe agitation, hallucinations, delusions, and dangerous actions requiring psychiatric hospitalization 4, 7
• Assess symptom presentation: approximately 46% present with delusions alone, 38% with hallucinations alone, and 15% with both manifestations 1
• Monitor for resolution: symptoms typically resolve within days to weeks after steroid reduction combined with antipsychotic treatment, though timing varies significantly between patients 1

Special Clinical Scenarios

When Steroids Cannot Be Discontinued

If the underlying condition requires continued high-dose corticosteroids, maintain antipsychotic therapy prophylactically while attempting gradual steroid taper 5, 7

• One successfully managed pediatric case continued risperidone prophylaxis throughout prolonged steroid treatment for nephrotic syndrome without recurrence of psychosis 5
• Alternative strategy: combine dose reduction with mood stabilizers (such as lithium) or antipsychotics for patients requiring ongoing steroid therapy 7, 1

High-Risk Populations Requiring Enhanced Surveillance

• Patients receiving >40 mg prednisone equivalent daily face the highest risk, as dose is the most significant risk factor for neuropsychiatric complications 2
• Patients with adrenal insufficiency treated with high-dose hydrocortisone (up to 400 mg/24 hours) during adrenal crisis require close psychiatric monitoring, as psychosis can emerge within 4 days of treatment initiation 4
• Elderly patients and those with prior psychiatric history warrant collaborative care between endocrinology/primary specialty and psychiatry 4

Critical Pitfalls to Avoid

• Do not delay antipsychotic treatment while waiting for steroid taper alone, as combined therapy is more effective than either intervention alone 1
• Do not abruptly discontinue steroids in patients with life-threatening underlying conditions (such as acute severe autoimmune hepatitis or adrenal crisis), as this may worsen the primary disease; instead, use antipsychotics to bridge the period until safe steroid reduction 3, 4
• Do not assume all psychiatric symptoms are steroid-induced without excluding other causes such as infection, metabolic derangements, or underlying disease progression 8
• Do not continue ineffective steroid therapy beyond 1-2 weeks in conditions like acute severe autoimmune hepatitis, as this increases psychiatric complication risk without therapeutic benefit 3

Evidence Quality Considerations

The evidence base consists primarily of case reports and case series rather than controlled trials, with the largest systematic review identifying only 13 definitive cases meeting DSM-5 criteria 1. Despite limited controlled data, the consistent pattern across multiple reports demonstrates that combination therapy (steroid dose reduction + antipsychotic) achieves symptom resolution in 100% of reported cases, though no notable adverse drug events were documented 1. The neuropsychiatric effects occur in approximately 6% of patients receiving steroids, making this a clinically significant complication requiring proactive management 2.