How can I diagnose steroid-induced confusion in an adult patient with a history of chronic illness or recent corticosteroid (e.g. prednisone, dexamethasone) therapy?

Diagnosing Steroid-Induced Confusion

Steroid-induced confusion is a clinical diagnosis based on temporal relationship: new or worsening confusion developing after starting corticosteroids, typically within the first few weeks of treatment, in the absence of other identifiable causes, and resolving with dose reduction or discontinuation. 1

Key Diagnostic Features

Psychiatric symptoms from steroids typically appear early in therapy, usually within the first 5 days to few weeks of treatment. 1, 2, 3 The presentation includes a spectrum of symptoms ranging from euphoria, mood swings, and emotional lability to severe depression, confusion, and frank psychotic manifestations. 4, 5

Characteristic Symptom Patterns

• Mood disorders occur in 93% of cases, with hypomania and mania being the most common acute presentations, though depression, severe anxiety, insomnia, and psychotic symptoms also occur. 1, 5, 6

• The symptom constellation includes: emotional lability, anxiety, distractibility, pressured speech, sensory flooding, insomnia, depression, perplexity, agitation, auditory and visual hallucinations, intermittent memory impairment, mutism, disturbances of body image, delusions, apathy, and hypomania. 3

• Cognitive changes are prominent, particularly deficits in declarative (verbal) and working memory. 5, 6

Risk Factors to Assess

Higher risk patients who warrant closer monitoring include: 1

• Female sex 1, 2
• Systemic lupus erythematosus 1, 2
• High-dose steroids (≥40 mg prednisone daily or equivalent) 1, 2, 3
• Prior steroid-induced psychiatric symptoms 1
• Elderly patients 1

Systematic Exclusion of Alternative Causes

Before attributing confusion to steroids, you must systematically exclude other etiologies. 1 This is not optional—alternative causes are common and potentially life-threatening.

Essential Laboratory Tests

• Basic metabolic panel (sodium, potassium, CO2, glucose) to detect hyponatremia, hyperkalemia, hypoglycemia, or uremia 1
• Random blood glucose to identify steroid-induced hyperglycemia 1
• Complete blood count to assess for infection or anemia 1
• Urinalysis and urine culture to exclude urinary tract infection 1

Critical Metabolic and Endocrine Considerations

• Adrenal insufficiency must be excluded, particularly in patients with recent steroid dose changes or tapering, as it can present with confusion, hypotension, and hyponatremia that mimics SIADH. 7 Morning cortisol with ACTH should be obtained if there is any suspicion. 7

• Steroid-induced hyperglycemia can cause altered mental status and must be ruled out. 1

• Hyponatremia is present in 90% of newly diagnosed adrenal insufficiency cases and can be indistinguishable from other causes without specific testing. 7

Physical Examination Priorities

• Vital signs with orthostatic blood pressure to detect hypotension suggesting adrenal insufficiency or dehydration 1
• Mental status examination documenting specific cognitive deficits, mood changes, and psychotic symptoms 1
• Neurological examination for focal deficits that would suggest stroke, mass lesion, or CNS infection 1

Selective Additional Testing

Brain imaging (CT or MRI), EEG, and lumbar puncture are necessary when: 1

• Focal neurological signs are present
• Fever without clear source
• Concern for seizures or CNS infection
• Atypical presentation or failure to improve with steroid dose reduction

Dose-Response Relationship

Psychiatric symptoms are dose-dependent. 5, 6 Patients receiving ≥40 mg prednisone daily (or equivalent) are at significantly greater risk. 2, 3 However, even lower doses can cause symptoms in susceptible individuals. 6

Critical Pitfalls to Avoid

• Do not assume confusion is steroid-induced without excluding infections (especially urinary tract infection, pneumonia, sepsis) and metabolic causes (hypoglycemia, hyponatremia, uremia). 1

• Do not overlook adrenal insufficiency, particularly in patients tapering steroids or with recent dose changes—this can be fatal if missed. 1

• Do not forget that even topical, inhaled, or intra-articular steroids can cause psychiatric symptoms and confusion. 1

• Do not miss steroid-induced hyperglycemia as a cause of altered mental status. 1

Confirming the Diagnosis

The diagnosis is confirmed by temporal relationship and response to intervention: 1

• Symptoms developed after starting or increasing corticosteroids
• No other cause identified after systematic workup
• Symptoms improve or resolve with dose reduction or discontinuation
• Symptoms recur if steroids are reintroduced (though rechallenge is not recommended)

Most patients recover within several weeks of dose reduction or discontinuation, though some may require pharmacologic treatment with antipsychotics or mood stabilizers during the acute phase. 2, 3