Prednisone-Induced Psychosis: Treatment and Risk Factors
Immediate Management
The first priority in treating prednisone-induced acute psychosis is to reduce or discontinue the corticosteroid if medically feasible, as psychosis typically resolves completely once the steroid is tapered or stopped. 1, 2, 3
Primary Treatment Algorithm
Discontinue or rapidly taper prednisone whenever the underlying medical condition permits, as this is the definitive treatment and symptoms usually resolve within days to weeks of cessation 1, 2, 3
If corticosteroids cannot be stopped due to the severity of the underlying condition (e.g., active lupus, severe asthma exacerbation), initiate antipsychotic medication while continuing necessary steroid therapy 2, 3
Involve psychiatry consultation promptly when neuropsychiatric symptoms develop, as specialized management improves outcomes 1
Antipsychotic Selection When Steroids Must Continue
Atypical antipsychotics are preferred over typical agents due to better tolerability and lower risk of extrapyramidal side effects 4
Risperidone 2 mg/day is an appropriate initial target dose for most patients with first-episode psychosis, including steroid-induced cases 4, 2
Olanzapine 7.5-10 mg/day represents an alternative first-line atypical antipsychotic option 4
Haloperidol (typical antipsychotic) has been used successfully in pediatric cases at 5 mg daily, though atypicals are generally better tolerated even at low doses 4, 3
Continue antipsychotic therapy throughout the duration of corticosteroid treatment if steroids cannot be discontinued 2
Risk Factors for Steroid-Induced Psychosis
Dose-Related Risk Factors
Doses >40 mg/day prednisone carry the highest risk, with neuropsychiatric complications rising rapidly above this threshold 1, 5
Doses >20 mg/day for >18 months are associated with severe psychiatric adverse effects in approximately 15% of patients 6, 7
However, psychosis can occur even at very low doses (as low as 2.5-15 mg/day), so dose alone does not exclude the diagnosis 8, 5
Patient-Specific Risk Factors
Prior history of steroid-induced psychosis or mania is the strongest predictor of recurrence and warrants prophylactic treatment with future steroid courses 1
Pre-existing bipolar disorder or psychiatric history significantly increases risk; the American Gastroenterological Association recommends avoiding prednisone entirely in these patients when possible 6
Damaged blood-brain barrier (from conditions like lupus cerebritis, CNS infections, or trauma) increases susceptibility to neuropsychiatric effects 1
Hypoalbuminemia increases free (unbound) corticosteroid levels and raises risk of psychiatric complications 1
Female sex confers higher susceptibility to glucocorticoid-related adverse events 7
Mood disturbances affect >30% of all patients taking corticosteroids, ranging from euphoria to severe depression and frank psychosis 6, 9
Timing Considerations
Acute reactions can occur within days of starting prednisone, even on the first dose in susceptible individuals 8
Symptoms typically appear within 2-4 weeks of initiation, making early psychiatric monitoring mandatory during this window 6
Prophylaxis for High-Risk Patients
When to Consider Prophylaxis
Patients with prior steroid-induced psychosis or mania should receive prophylactic treatment when future corticosteroid courses are prescribed, as this reduces recurrence risk 1
Patients with bipolar disorder requiring unavoidable corticosteroid therapy warrant prophylactic psychiatric medication 6
Prophylactic Medication Options
Lithium and olanzapine represent the best-supported choices for prophylaxis based on available trial data 1
Close psychiatric monitoring between 2-4 weeks is mandatory for all patients, evaluating for mood instability, sleep disturbances, agitation, and psychotic symptoms 6
Alternative Corticosteroid Strategies
Steroid-Sparing Approaches
Avoid prednisone/prednisolone entirely in patients with bipolar disorder or history of steroid psychosis when alternative treatments exist 6
Budesonide 9 mg/day plus azathioprine 1-2 mg/kg/day (in non-cirrhotic patients) produces significantly fewer psychiatric side effects than systemic prednisolone, per European Association for the Study of the Liver guidelines 6
Limit prednisone courses to ≤6 weeks whenever possible, as duration >6 weeks markedly increases risk of serious complications including psychiatric effects 7
Critical Pitfalls to Avoid
Do not dismiss psychosis in patients on <40 mg/day prednisone—case reports document acute psychosis at doses as low as 2.5-15 mg daily 8, 5
Do not attribute all psychotic symptoms to the underlying disease (e.g., lupus cerebritis)—steroid-induced psychosis is a diagnosis of exclusion requiring neurology consultation to rule out CNS involvement of the primary condition 3
Do not continue high-dose steroids without psychiatric consultation once psychosis develops—prompt involvement of psychiatry improves outcomes 1
Do not fail to warn patients and caregivers about potential neuropsychiatric complications before initiating corticosteroids, as early recognition facilitates rapid intervention 1
Do not assume psychosis will resolve while continuing steroids—in most cases, complete resolution requires steroid discontinuation or significant dose reduction 2, 3
Special Populations
Pediatric Considerations
Mean age of steroid-induced psychosis in children is 12 ± 3.6 years, with cases reported in patients with asthma, autoimmune diseases, and cancer 3
Risperidone has been used successfully in adolescents with steroid-induced psychosis, including as maintenance therapy when steroids cannot be discontinued 2
Symptoms in children may include mutism, drooling, responding to internal stimuli, and behavioral changes within days of starting prednisone 3