Can Prednisone Cause Psychosis in a Bipolar Patient?
Yes, prednisone can absolutely cause psychosis in bipolar patients, and these patients are at particularly high risk for severe psychiatric decompensation, including manic episodes and psychosis, when exposed to corticosteroids. 1, 2
Risk Profile in Bipolar Patients
Bipolar disorder represents a specific vulnerability to corticosteroid-induced psychiatric symptoms. The FDA drug label explicitly warns that corticosteroids can cause "psychiatric derangements ranging from euphoria, insomnia, mood swings, personality changes, and severe depression, to frank psychotic manifestations," and notes that "existing emotional instability or psychotic tendencies may be aggravated by corticosteroids." 1
Key Evidence:
A recent case report (2025) documented a patient with subthreshold bipolar disorder who developed a severe manic episode requiring psychiatric hospitalization within one week of receiving intravenous corticosteroids for asthma. 2 After initial remission with olanzapine, she experienced recurrent mania, confirming the diagnosis had progressed to full bipolar disorder. 2
The similarities between corticosteroid-induced psychiatric symptoms and bipolar disorder are well-established, with symptoms of hypomania, mania, depression, and psychosis being common during therapy. 3
Mood disturbances occur in over 30% of patients taking corticosteroids, with the spectrum ranging from euphoria to severe depression and frank psychosis. 4, 1
Dose and Timing Considerations
While higher doses carry greater risk, psychosis can occur even at low doses:
Patients receiving ≥40 mg/day of prednisone are at greatest risk, but psychosis has been documented with doses <40 mg/day. 5, 6
Psychotic reactions are twice as likely to occur during the first 5 days of treatment compared to later periods. 6
Severe adverse effects, including psychosis, occur mainly at doses >20 mg/day for more than 18 months, but acute reactions can happen much sooner. 7, 4
Clinical Management Algorithm
When Corticosteroids Are Being Considered:
Avoid prednisone/prednisolone entirely if possible in patients with bipolar disorder or history of steroid-induced psychosis. 7, 8
If corticosteroids are absolutely necessary:
In non-cirrhotic patients (e.g., autoimmune hepatitis), use budesonide 9 mg/day plus azathioprine 1-2 mg/kg/day instead of systemic prednisolone, as this combination has significantly fewer psychiatric side effects (26% vs 51.5% steroid side effects). 7, 8
Limit duration to 7-10 days maximum when possible, as extending beyond this carries no additional benefit in acute conditions and increases psychiatric risk. 8
Close psychiatric monitoring is mandatory:
If Psychosis Develops:
Antipsychotics (particularly phenothiazines) are highly effective, with average daily doses of 212 mg producing excellent response in steroid psychosis cases. 6
Avoid tricyclic antidepressants, as they have been shown to exacerbate or worsen steroid-induced psychiatric symptoms. 6
Consider atypical antipsychotics like olanzapine, which successfully treated the severe manic episode in the recent bipolar case. 2
Critical Pitfalls to Avoid
Do not assume that absence of prior psychiatric hospitalization means low risk - patients with subthreshold bipolar symptoms are still highly vulnerable to corticosteroid-induced decompensation. 2
Do not exclude steroid-induced psychosis from the differential simply because the dose is <40 mg/day - psychosis can occur at any dose. 5
Do not underestimate the severity of potential psychiatric reactions - these can progress rapidly to require psychiatric hospitalization within days. 2
In patients with known bipolar disorder, premorbid psychiatric history does not reliably predict risk during any given course of therapy, so vigilance is required regardless of past stability. 6