Mrs. E, age 31, develops rapid, pressured speech and insomnia for 4 consecutive nights, but reports a normal energy level after receiving high-dose methylprednisolone for an acute flare of systemic lupus erythematosus (SLE).
Her medical history indicates an overlap syndrome between SLE and systemic sclerosis for the last 5 years, migraine headaches, and 4 spontaneous miscarriages, but she has no psychiatric history. Her family history is negative for psychiatric illness and positive for diabetes mellitus, hypertension, and coronary artery disease.
Mrs. E lives with her husband and 10-year-old son. She admits to multiple stressors, including her health problems and financial dificulties, which recently led to the family’s decision to move to her mother-in-law’s house. Mrs. E denies using illicit drugs, cigarettes, or alcohol.
Mrs. E is admitted to the hospital, and her corticosteroid dosage is reduced with a switch to prednisone, 60 mg/d. She is started on risperidone, 1 mg at bedtime, which is titrated without adverse effect. Her psychotic symptoms improve over 4 days, and she is discharged on prednisone, 60 mg/d, and risperidone, 0.5 mg in the morning and 2 mg at night.
After completing her corticosteroid course, Mrs. E experiences complete resolution of psychiatric symptoms and is tapered off risperidone after 6 months.
Corticosteroid use can cause a variety of psychiatric syndromes, including mania, psychosis, depression, and delirium. A meta-analysis reports severe psychotic reactions in 5.7% of patients taking corticosteroids and mild-to-moderate reactions in 28% of patients.1 Hypomania, mania, and psychosis are the most common psychiatric reactions to acute corticosteroid therapy.2 This article reviews case reports and open-label trials of antipsychotics, mood stabilizers, and anticonvulsants to treat corticosteroid-induced mania and psychosis and outlines treatment options.
Symptoms
Corticosteroid-induced psychosis represents a spectrum of psychological changes that can occur at any time during treatment. Mild-to-moderate symptoms include agitation, anxiety, insomnia, irritability, and restlessness, whereas severe symptoms include mania, depression, and psychosis.3 Case reports reveal:
- mania and hypomania in 35% of patients with corticosteroid-induced psychosis
- acute psychotic disorder in 24% of patients, with hallucinations reported in one-half of these cases
- depression, which is more common with chronic corticosteroid therapy, in 28% of patients.4
Delirium and cognitive deficits also have been reported, although these symptoms generally subside with corticosteroid reduction or withdrawal.4,5
Psychiatric symptoms often develop after 4 days of corticosteroid therapy, although they can occur late in therapy or after treatment ends.6 Delirium often resolves within a few days, psychosis within 7 days, and mania within 2 to 3 weeks, whereas depression can last for more than 3 weeks.4 A 3-level grading system can gauge severity of corticosteroid-induced psychosis; grade 2 or 3 warrants treatment (Table 1).4
Table 1
Grading scale for corticosteroid-induced psychiatric symptoms
| Grade | Symptoms |
|---|---|
| Grade 1 | Mild, nonpathologic, and subclinical euphoria |
| Grade 2 | Reversible acute or subacute mania and/or depression |
| Grade 3 | Bipolar disorder with relapses possible without steroids |
| Source: Reference 4 | |
Risk factors
High corticosteroid dose is the primary risk factor for psychosis. The Boston Collaborative Drug Surveillance Program reported that among individuals taking prednisone, psychiatric disturbances are seen in:
- 1.3% of patients taking <40 mg/d
- 4.6% of patients taking 40 to 80 mg/d
- 18.4% of patients taking >80 mg/d.7
However, the corticosteroid dosage does not predict onset, severity, type of reaction, or duration.3,7 Female patients are at higher risk of corticosteroid-induced psychosis, even after one controls for medical conditions diagnosed more often in women, such as SLE and rheumatoid arthritis.3 Previous episodes of corticosteroid-induced psychosis, history of psychiatric illness, and age are not associated with corticosteroid-induced psychosis.3
Treatment
Management includes tapering corticosteroids, with or without adding medications to treat the acute state. Decreasing corticosteroids to the lowest dose possible—<40 mg/d—or gradually discontinuing therapy to prevent triggering adrenal insufficiency may improve psychotic symptoms and avoids the risk of adverse effects from adjunctive medications.
Psychopharmacologic treatment may be necessary, depending on the severity of psychosis or the underlying disease, particularly if corticosteroids cannot be tapered or discontinued. Evidence from open-label trials (Table 2)8-12 and case reports indicates that psychotic symptoms could be prevented and treated with off-label antipsychotics, mood stabilizers, and anticonvulsants.
Consider your patient’s underlying medical condition when selecting psychotropics. For example, try to avoid prescribing:
- antipsychotics to patients with cardiac conduction abnormalities
- lithium to patients who need diuretic or angiotensin-converting enzyme inhibitor therapy or those with underlying renal insufficiency.
When appropriate, collaborate with the provider who prescribed the corticosteroids because tapering or discontinuation might not be possible.
Table 2