What is the best course of treatment for a patient with suspected steroid-induced psychosis, particularly those with a history of psychiatric disorders or taking high doses of steroids like prednisone?

Steroid-Induced Psychosis: Treatment Algorithm

Immediately reduce or discontinue the corticosteroid and initiate an atypical antipsychotic if symptoms are severe. 1

Immediate Management

**The cornerstone of treatment is steroid dose reduction to <20 mg/day prednisone equivalent or complete discontinuation if the underlying condition permits.** 1 This addresses the root cause, as severe psychiatric adverse effects including psychosis occur mainly at doses >20 mg/day, particularly after prolonged use beyond 18 months, though acute reactions can develop within days. 2, 3

Steroid Modification Strategy

• Reduce prednisone to the minimum effective dose immediately (ideally <20 mg/day), as this is where severe psychiatric effects become prominent. 2, 1

• In non-cirrhotic patients requiring continued immunosuppression, switch to budesonide 9 mg/day plus azathioprine 1-2 mg/kg/day, as this combination demonstrates significantly fewer psychiatric side effects (26.0% vs 51.5% with prednisone). 2, 1

• For patients with pulmonary sarcoidosis or autoimmune conditions, decrease the starting steroid dose in the presence of psychosis (consensus score 3.68±2.01), recognizing this as a high-risk comorbidity. 2

Antipsychotic Treatment

Atypical antipsychotics are preferred over typical agents due to superior side effect profiles. 1 The evidence from pediatric and adult case series shows:

• Risperidone and haloperidol are the most commonly used agents, with haloperidol being most frequently prescribed in case reports, followed by risperidone. 4, 5, 6

• All patients in systematic reviews returned to psychological baseline when antipsychotic therapy was combined with steroid dose reduction or discontinuation, though time to resolution varied. 6

• In one pediatric case requiring ongoing steroid therapy for nephrotic syndrome, risperidone was successfully used both for treatment and prophylaxis during continued corticosteroid administration. 5

Critical Timing Considerations

Psychotic symptoms can emerge within days of steroid initiation, even at doses as low as 10-15 mg/day prednisone, particularly in vulnerable populations. 7 One case documented acute psychosis after the first dose of 10 mg prednisolone in a patient with Sheehan's syndrome, with recurrence at just 2.5 mg/day upon rechallenge. 7

Symptoms typically resolve within days to weeks after steroid discontinuation combined with antipsychotic therapy, though the timeline is variable. 6

High-Risk Populations Requiring Aggressive Avoidance

Patients with pre-existing psychiatric conditions (bipolar disorder, schizophrenia, prior steroid-induced psychosis) are at substantially higher risk and require alternative immunosuppression strategies. 1, 8

Prevention Strategy for High-Risk Patients:

• Avoid systemic corticosteroids entirely if possible. 1, 8

• If steroids are absolutely necessary, use budesonide 9 mg/day plus azathioprine rather than systemic prednisolone in non-cirrhotic patients. 1, 8

• Consider alternative immunosuppression (azathioprine, methotrexate, mycophenolate) as first-line therapy in patients with psychiatric history. 2, 1

• Limit steroid duration to 7-10 days maximum in acute conditions, as extending beyond this provides no additional benefit and increases psychiatric risk. 1, 8

Common Pitfalls to Avoid

Do not assume psychosis is due to the underlying disease (e.g., lupus cerebritis) without first considering steroid-induced psychosis, especially when symptoms emerge shortly after steroid initiation. 4 In one pediatric lupus case, extensive workup ruled out lupus cerebritis, and symptoms only resolved after complete steroid discontinuation. 4

Do not continue high-dose steroids while attempting to treat psychosis with antipsychotics alone—this approach is less effective than combining steroid reduction with antipsychotic therapy. 6

Recognize that steroid withdrawal itself can cause psychiatric symptoms (depression, malaise, arthralgia), requiring gradual taper when possible rather than abrupt discontinuation. 3

Monitoring Protocol

Evaluate patients at 2-4 weeks for symptomatic response and psychiatric side effects, including mood instability, sleep disturbances, agitation, and psychotic symptoms. 8, 9

For patients requiring steroid continuation, maintain close psychiatric monitoring and consider prophylactic antipsychotic therapy if psychosis was severe. 5