How do I diagnose steroid-induced confusion in a patient, particularly in the elderly or those with a history of psychiatric disorders, who are receiving corticosteroids (corticosteroid therapy)?

Diagnosing Steroid-Induced Confusion

Steroid-induced confusion is a clinical diagnosis based on temporal relationship: new or worsening confusion that develops after starting corticosteroids (typically within days to weeks), occurs in the absence of other identifiable causes, and resolves with dose reduction or discontinuation of the steroid. 1, 2, 3

Key Diagnostic Features

Temporal Relationship

• Psychiatric symptoms typically appear early in steroid therapy, usually within the first few weeks of treatment 2, 3
• Confusion can develop even with topical steroid preparations (e.g., steroid eye drops) 4
• The onset is often acute to subacute rather than gradual 1, 3

Clinical Presentation Patterns

Steroid-induced psychiatric disturbances manifest in several forms, with confusion being part of a broader spectrum:

• Mood disorders (93% of cases): euphoria, mood swings, severe depression 1, 5
• Psychotic symptoms: delusions, hallucinations, paranoia 2, 3, 6
• Delirium/acute confusional state: fluctuating consciousness, decreased attention, disorientation 1, 3, 7
• Cognitive impairment: memory problems, difficulty concentrating 3
• Anxiety, insomnia, personality changes, and frank psychotic manifestations 5, 3

Distinguishing Features from Other Causes

You must systematically exclude alternative etiologies before attributing confusion to steroids: 1

Immediate exclusions required:

• Infections (especially CNS infections, urinary tract infections, pneumonia) - Check vital signs for fever, obtain urinalysis, chest X-ray, and consider lumbar puncture if CNS infection suspected 1
• Metabolic disturbances - Measure sodium, potassium, glucose, calcium, BUN/creatinine 1
• Hypoglycemia or steroid-induced hyperglycemia - Random blood glucose ≥11.1 mmol/L suggests steroid-induced diabetes 1
• Hyponatremia - Can occur with adrenal insufficiency or SIADH; present in 90% of adrenal insufficiency cases 1, 8
• Seizure activity - Obtain EEG if seizures suspected 1
• Structural brain lesions - Brain imaging (CT or MRI) indicated if focal neurological signs, head trauma history, or fever present 1

Drug-related considerations:

• Review all medications for interactions or other causes of confusion 1
• Corticosteroid dose matters: psychiatric reactions occur in ~5% of patients overall, but risk increases significantly with prednisone ≥1 mg/kg or doses >20 mg/day 1, 2
• Dexamethasone triggers greater hyperglycemia than prednisone, with peak effects 7-9 hours post-dose 1

Diagnostic Workup Algorithm

Step 1: Establish Temporal Relationship

• Document when steroids were started or dose increased 2, 3
• Document when confusion began relative to steroid initiation 2, 4
• Note the specific steroid, dose, and route (oral, IV, topical, inhaled) 1, 4

Step 2: Perform Focused History

• Previous psychiatric history - Prior steroid-induced psychiatric reactions are a risk factor for recurrence 2, 7
• Female sex and systemic lupus erythematosus - Both increase risk of steroid-induced psychiatric syndromes 2
• Symptoms of infection: fever, cough, dysuria, diarrhea 1
• Recent head trauma or neurological symptoms 1
• Salt cravings, orthostatic symptoms (suggests adrenal insufficiency) 8

Step 3: Physical Examination Priorities

• Vital signs including orthostatic blood pressure - Hypotension suggests adrenal insufficiency 1, 8
• Mental status examination with specific attention to level of consciousness, orientation, attention span 1
• Neurological examination for focal deficits 1
• Skin examination for hyperpigmentation (primary adrenal insufficiency) vs normal color (secondary adrenal insufficiency or steroid effect) 8

Step 4: Essential Laboratory Tests

• Basic metabolic panel: sodium, potassium, glucose, BUN, creatinine 1
• Random blood glucose - More sensitive than fasting for steroid-induced hyperglycemia 1
• Complete blood count 1
• Urinalysis and urine culture 1
• If hyponatremia present: serum and urine osmolality, urine sodium - To distinguish SIADH from adrenal insufficiency 8

Step 5: Selective Additional Testing

• Brain imaging (CT or MRI) if: focal neurological signs, fever without clear source, history of malignancy, head trauma, or initial workup unrevealing 1
• EEG if: concern for seizures or to help diagnose delirium (shows generalized slowing) 1
• Lumbar puncture if: fever with confusion to exclude CNS infection 1
• Morning cortisol and ACTH if adrenal insufficiency suspected - But note these are unreliable in patients actively taking corticosteroids 1, 8

Making the Diagnosis

The diagnosis is confirmed when:

1. Confusion developed temporally related to steroid initiation or dose increase 2, 4, 3
2. Alternative causes have been systematically excluded 1
3. Symptoms improve or resolve with steroid dose reduction or discontinuation 2, 3, 6

Most patients recover within several weeks of symptom onset once steroids are tapered or stopped 2, 6

Critical Pitfalls to Avoid

• Do not assume confusion is steroid-induced without excluding infections and metabolic causes - History and physical examination have 94% sensitivity for identifying medical conditions in psychiatric patients 1
• Do not overlook adrenal insufficiency in patients with confusion who are on chronic steroids or recently stopped steroids - This can present identically to SIADH with hyponatremia and confusion 8
• Do not miss steroid-induced hyperglycemia - Occurs in up to 39.5% of patients on steroids and can cause altered mental status 1
• Do not forget that even topical steroids (eye drops) can cause confusion, particularly in the elderly 4
• Female patients and those with prior steroid-induced psychiatric reactions are at higher risk 2, 7

Risk Stratification

Higher risk patients who warrant closer monitoring: 2, 7

• Female sex
• Systemic lupus erythematosus diagnosis
• High-dose steroids (prednisone ≥1 mg/kg or >20 mg/day)
• Prior steroid-induced psychiatric symptoms
• Elderly patients (though age itself is not an independent risk factor)