What is the appropriate management for steroid‑induced mania, including dose reduction and selection of mood‑stabilizing or antipsychotic therapy?

Management of Steroid-Induced Mania

When steroid-induced mania occurs, immediately reduce the corticosteroid dose by 25-33% while simultaneously initiating sodium valproate 500 mg twice daily, which rapidly reverses manic symptoms within 48-72 hours without requiring complete steroid discontinuation. 1

Immediate Pharmacologic Management

First-Line Treatment: Sodium Valproate

• Start sodium valproate 500 mg twice daily immediately upon recognition of manic symptoms 1
• Measure valproate levels on day 3 to adjust dosing as needed 1
• Expect significant symptom improvement within 48 hours, with complete resolution to euthymia by 72 hours 1
• This approach allows continuation of medically necessary corticosteroid therapy while controlling psychiatric symptoms 1
• Monitor for hyperammonemia, though this is rare and resolves with drug discontinuation 1

Alternative: Olanzapine

• Begin olanzapine at 2.5 mg/day if valproate is contraindicated or not tolerated 2
• Titrate upward as necessary to maximum 20 mg/day based on symptom response 2
• Expect significant reductions in manic symptoms over 5 weeks with good tolerability 2
• Monitor weight and blood glucose, though significant changes are uncommon at these doses 2

Concurrent Corticosteroid Dose Management

Dose Reduction Strategy

• Reduce corticosteroid dose by 25-33% immediately when mania develops 3
• Expert consensus strongly supports dose reduction for patients with psychosis (consensus score 3.68±2.01) 3
• Continue tapering to the lowest dose that maintains control of the underlying medical condition 3

When Steroids Cannot Be Reduced

• If the underlying medical condition requires continued high-dose corticosteroids, proceed with mood stabilizer or antipsychotic therapy without dose reduction 1, 2
• Sodium valproate's rapid action (48-72 hours) makes it particularly valuable when steroids must be continued 1

Critical Clinical Considerations

Dose-Dependent Risk

• Psychiatric adverse effects occur in approximately 6% (severe) and 28% (mild-to-moderate) of patients on corticosteroids 4
• Dosage directly correlates with incidence of adverse effects, but NOT with timing, severity, or duration of symptoms 4
• Short-term therapy typically causes euphoria and hypomania, while long-term therapy tends toward depressive symptoms 4

Unpredictable Recurrence

• Previous tolerance of corticosteroids does NOT predict future tolerance—patients can develop mania even after previously tolerating higher doses 5
• Neither presence nor absence of previous reactions predicts adverse responses to subsequent courses 4
• Exercise caution when restarting steroids even at low doses in patients with prior psychiatric symptoms 5

Underlying Bipolar Disorder Risk

• Screen for subthreshold bipolar symptoms before initiating corticosteroids, as even mild mood instability increases risk of severe manic episodes 6
• Corticosteroids can unmask or severely worsen previously undiagnosed bipolar disorder 6
• If severe mania develops, consider that the patient may have underlying bipolar disorder requiring ongoing psychiatric treatment even after steroid discontinuation 6

Treatment Algorithm

1. Recognize manic symptoms early (irritability, decreased sleep need, pressured speech, grandiosity, disruptive behavior) 1
2. Immediately initiate sodium valproate 500 mg twice daily 1
3. Simultaneously reduce corticosteroid dose by 25-33% if medically feasible 3
4. Measure valproate level on day 3 and adjust dose accordingly 1
5. Reassess at 48-72 hours—expect significant to complete symptom resolution 1
6. If inadequate response, consider switching to olanzapine 2.5-20 mg/day 2
7. Continue tapering steroids to lowest effective dose for underlying condition 3

Common Pitfalls to Avoid

• Do NOT assume previous steroid tolerance predicts future safety—mania can occur even after prior uneventful courses 5
• Do NOT delay mood stabilizer initiation while attempting steroid dose reduction alone—combined approach is most effective 1
• Do NOT discontinue steroids abruptly unless medically safe—sodium valproate allows psychiatric symptom control while continuing necessary medical therapy 1
• Do NOT overlook underlying bipolar disorder—if symptoms persist after steroid discontinuation, ongoing psychiatric treatment is required 6