A 28-year-old man with severe asthma exacerbation is admitted to the ICU. He receives intravenous hydrocortisone 100 mg every 6 hours for acute airway inflammation. On day 3, he develops acute psychosis with visual hallucinations, insomnia, and agitation. His vital signs are stable, and sepsis workup is negative. Serum glucose is 320 mg/dL, and serum calcium is 7.8 mg/dL (corrected). Which corticosteroid-related adverse effect best explains his psychiatric symptoms?

Explanation

## Corticosteroid-Induced Psychosis **Key Point:** Corticosteroid-induced psychiatric symptoms are a direct dose-dependent effect of glucocorticoids on the central nervous system, not secondary to metabolic derangements. ### Mechanism of Corticosteroid Psychosis **High-Yield:** Glucocorticoids cross the blood–brain barrier and bind to glucocorticoid receptors (GR) in the limbic system, particularly: - Amygdala (emotional processing) - Hippocampus (memory and stress response) - Prefrontal cortex (executive function) This leads to: 1. **Altered monoamine metabolism** — decreased serotonin and dopamine turnover 2. **Increased glutamatergic activity** — excitatory neurotransmission 3. **GABA dysregulation** — reduced inhibitory tone 4. **Cytokine modulation** — paradoxical neuroinflammation at high doses ### Clinical Features of Corticosteroid Psychosis | Feature | Timing | Severity | Reversibility | | --- | --- | --- | --- | | Insomnia | Day 1–2 | Mild | Complete | | Anxiety/agitation | Day 2–3 | Moderate | Complete | | Mood elevation (hypomania) | Day 3–5 | Moderate | Complete | | Psychosis (hallucinations, delusions) | Day 3–7 | Severe | Complete (if caught early) | | Depression | Week 2+ | Variable | Complete | **Clinical Pearl:** This patient's presentation on day 3 with visual hallucinations and agitation is classic for corticosteroid-induced psychosis. The onset correlates with cumulative dose (hydrocortisone 400 mg/day = 100 mg dexamethasone equivalent, a very high dose). ### Risk Factors for Corticosteroid Psychosis - **Dose:** >40 mg/day prednisolone equivalent (or >100 mg hydrocortisone/day) - **Duration:** Acute high-dose therapy (first 3–7 days) - **Route:** IV administration carries higher risk than oral - **Patient factors:** Prior psychiatric history, female gender, older age - **Drug interactions:** Concurrent stimulants, anticholinergics **Mnemonic:** **PSYCH** — Prednisolone/Prednisone, Steroids, Ypsilateral limbic effects, Cortisol excess, High-dose therapy ### Management 1. **Reduce corticosteroid dose** if clinically feasible (taper to maintenance) 2. **Antipsychotic:** Haloperidol 5–10 mg IM or olanzapine 5–10 mg PO 3. **Benzodiazepine:** Lorazepam 2–4 mg for acute agitation 4. **Sleep hygiene:** Melatonin, avoid stimulants 5. **Monitor:** Symptoms typically resolve within 3–7 days of dose reduction **Warning:** Do NOT attribute this to sepsis, hypoglycemia, or electrolyte abnormalities without ruling out corticosteroid psychosis first. The negative sepsis workup and normal vital signs make infection unlikely. [cite:Harrison 21e Ch 377; KD Tripathi 8e Ch 56]