Steroid-Induced Psychosis: How to Recognize and Treat It in an Emergency

When Steroids Trigger Psychosis: A Real Emergency

Imagine someone on high-dose steroids for a flare-up of lupus or severe asthma suddenly starts talking to people who aren’t there, believes they’re being watched, or becomes wildly agitated. It’s not a mental illness they’ve always had. It’s not drug abuse. It’s not delirium from infection. It’s steroid-induced psychosis - and it can happen fast, often within days of starting treatment. This isn’t rare. Around 6% of people on high-dose steroids develop severe psychiatric symptoms, and at doses over 80 mg of prednisone daily, that number jumps to nearly 1 in 5. Most emergency doctors don’t expect it. But if you’re prescribing or caring for someone on steroids, you need to.

How It Starts: The First Warning Signs

Steroid-induced psychosis doesn’t usually begin with full-blown hallucinations. It starts quietly. A patient who was calm and cooperative suddenly seems confused, restless, or overly emotional. They might stare blankly, repeat questions, or get angry over small things. These early signs - agitation, confusion, irritability - show up in the first 1 to 5 days after starting or increasing a steroid dose. That’s the window to act.

Studies tracking hundreds of patients show a clear pattern: the higher the steroid dose, the higher the risk. At 40 mg of prednisone per day, about 4.6% of patients develop psychiatric symptoms. At 80 mg or more, that rises to 18.4%. It’s not about how long you’ve been on steroids - it’s about how much you’re taking right now. Even short courses can trigger mania or psychosis. And it’s not just prednisone. Dexamethasone, methylprednisolone, and other synthetic corticosteroids carry the same risk.

What It Looks Like: Beyond the Myths

People assume psychosis means hearing voices and seeing ghosts. But steroid-induced psychosis often looks different. In one review of 79 cases, 40% had depression, 28% had mania, and only 14% had full-blown psychosis. Many patients aren’t hallucinating - they’re just deeply irritable, euphoric in a reckless way, or emotionally flat. Others have racing thoughts, sleeplessness, or grandiose beliefs - like thinking they can cure themselves or that they’re invincible.

What makes this dangerous is how easily it’s missed. A patient on steroids for COPD who starts yelling at nurses might be labeled as ‘difficult’ or ‘noncompliant.’ A teenager on high-dose steroids for nephrotic syndrome who stops sleeping and starts spending money recklessly might be thought of as ‘going through a phase.’ But if these changes happen after starting steroids, and no other cause fits, it’s likely steroid-induced. The DSM-5 says you must rule out everything else: infections, low sodium, high blood sugar, brain tumors, seizures, or other drugs before you can say it’s from steroids.

Why It Happens: The Brain on Steroids

Steroids aren’t just anti-inflammatory. They cross the blood-brain barrier and bind to receptors in areas that control mood, memory, and perception. High doses flood the system, disrupting the balance between glucocorticoid and mineralocorticoid receptors. This throws off the HPA axis - the body’s stress response system - and mimics what happens in Cushing’s syndrome, where the body makes too much cortisol naturally.

It’s not fully understood why some people are more vulnerable. But genetics likely play a role. Some people’s brains just react more strongly to synthetic cortisol. That’s why researchers at the NIH are now studying 500 patients on high-dose steroids to find genetic markers that predict who’s at risk. Until then, we treat everyone on high doses like they could be vulnerable.

Emergency Response: What to Do Right Now

If someone is agitated, aggressive, or clearly out of touch with reality after starting steroids, the first priority is safety - for them and everyone around them. Don’t wait. Don’t assume they’ll calm down. Don’t assume it’s ‘just behavior.’

1. De-escalate first. Use calm, low tones. Remove crowds. Turn down lights. Offer water. Don’t corner them.
2. Check for medical mimics. Order blood tests: glucose, sodium, potassium, calcium, liver and kidney function, CRP, and blood cultures. Hyperglycemia from steroids can worsen confusion. Infections like UTIs or pneumonia can trigger delirium that looks like psychosis.
3. Confirm steroid exposure. What steroid? What dose? When did they start? Did they just increase it? Timing matters. Symptoms that begin within five days are far more likely to be steroid-related.
4. Start treatment. If they’re too agitated to take pills, give IM olanzapine (5-10 mg) or IM haloperidol (2-5 mg). If using haloperidol, give diphenhydramine or benztropine to prevent stiff muscles or tremors. Avoid high doses - 20-30 mg of oral olanzapine is dangerous here. Stick to 2.5-20 mg total per day. Most patients improve in 2-7 days.

Physical restraints? Only if they’re trying to hurt themselves or others. Restraints can make psychosis worse. They’re not a treatment - they’re a last resort.

The Real Fix: Taper the Steroids

Medications help calm the symptoms, but they don’t fix the root cause. The only way to truly reverse steroid-induced psychosis is to lower the dose. In 92% of cases, symptoms fully resolve when steroids are reduced to below 40 mg of prednisone per day (or the equivalent in other steroids).

But here’s the catch: you can’t just stop steroids cold. If someone is on them for a life-threatening condition - like a transplant, severe autoimmune disease, or adrenal insufficiency - stopping abruptly can kill them. That’s why tapering has to be smart. Work with the prescribing specialist. Can you drop from 120 mg to 60 mg? Then to 40 mg? Then 20 mg? Do it over days, not hours. Monitor for withdrawal signs: fatigue, joint pain, nausea, low blood pressure.

If the underlying disease can’t be controlled without steroids, you may need to keep them on a low dose long-term - and manage the psychosis with ongoing antipsychotics. Olanzapine, risperidone, and haloperidol are the most studied. Lithium can help prevent mania, but it’s risky with kidney or thyroid issues. Antidepressants or seizure meds like valproate might help in some cases, but the evidence is weaker.

What Most Hospitals Get Wrong

A 2022 survey of 127 emergency doctors found that while 89% knew steroids could cause psychosis, only 43% followed the recommended tapering protocol. More than half gave antipsychotic doses meant for schizophrenia - double or triple what’s needed for steroid-induced cases. That’s not just unnecessary - it’s dangerous. High doses of haloperidol can cause dangerous heart rhythms. Too much olanzapine can cause sedation, low blood pressure, or even aspiration.

The American College of Emergency Physicians updated its guidelines in March 2023 to say this clearly: for medication-induced psychosis, use 50-75% of the usual antipsychotic dose. Start low. Go slow. Watch for side effects. And always, always try to reduce the steroid first.

What’s Coming Next

There’s hope on the horizon. The NIH study tracking 500 patients on high-dose steroids is expected to release its first data in late 2024. It’s looking for genetic markers - maybe a variant in the glucocorticoid receptor gene - that could tell doctors ahead of time who’s at highest risk. If you’re planning to start someone on 80 mg of prednisone, wouldn’t you want to know if they’re genetically prone to psychosis?

The American Psychiatric Association is also developing a clinical decision tool, due out in mid-2025, that will help emergency and primary care teams make faster, safer decisions. It will ask: What’s the steroid dose? How long have they been on it? Any prior mental health history? Any electrolyte issues? Then it will suggest: taper now? Start antipsychotic? Run these labs?

Bottom Line: Don’t Wait for the Worst

Steroid-induced psychosis is one of the most treatable forms of psychosis - if you catch it early. It’s not a psychiatric emergency. It’s a medical emergency. The fix isn’t more antipsychotics. It’s less steroids. And the sooner you act, the better the outcome.

If you’re prescribing steroids - especially above 40 mg/day - talk to your patient and their family. Warn them: ‘You might feel anxious, restless, or have trouble sleeping. If you start seeing or hearing things that aren’t real, or feel like you’re losing control, call us immediately.’

If you’re in the ER and someone shows up with sudden psychosis - check their meds. Ask: ‘Are they on steroids?’ If yes, don’t assume it’s schizophrenia. Don’t just give a high dose of haloperidol and send them home. Treat the cause. Taper the steroid. Give the right dose of antipsychotic. And save someone from months of unnecessary suffering.