Evidence-Based Reviews

Corticosteroid-induced mania: Prepare for the unpredictable

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Head off this common psychiatric side effect.


 

References

Can corticosteroids “unlock” hidden potential for mania, or are steroid-induced mood symptoms a temporary reaction? And when these mood symptoms occur, what is the best way to treat them?

Psychiatric symptoms develop in 5% to 18% of patients treated with corticosteroids. These effects—most often mania or depression—emerge within days to weeks of starting steroids. To help you head off manic and mixed mood symptoms, this paper examines how to:

  • treat steroid-induced mania or mixed bipolar symptoms
  • reduce the risk of a mood episode in patients who require sustained corticosteroid therapy.

‘Steroid psychosis’

Jane Pauley, NBC’s Today Show broadcaster, described in her autobiography how hypomania developed within weeks after she started corticosteroids for idiopathic urticaria edema: “I was so energized that I didn’t just walk down the hall, I felt like I was motoring down the hall. I was suddenly the equal of my high-energy friends who move fast and talk fast and loud. I told everyone that I could understand why men felt like they could run the world, because I felt like that. This was a new me, and I liked her!”1

Pauley’s hypomania led to a manic episode and eventually to depression. She was started on antidepressants, which triggered another manic episode. Pauley—who had no history of bipolar disorder—spent 3 weeks in a New York psychiatric hospital.1

Diagnostic symptoms. Corticosteroids’ psychiatric effects—cognitive, mood, anxiety, and psychotic symptoms—were first described as “steroid psychosis.” Psychosis can occur, but mood symptoms are more common:

  • Among 122 patients, 40% experienced depression, followed by mania (28%), psychosis (14%), delirium (10%), and mixed mood episodes (8%).2
  • Among 130 patients, mania was most prevalent (35%), followed by depression (28%), mixed mood episodes (12%), delirium (13%), and psychosis (11%).3
  • Corticosteroids caused 54% of organic mania cases on a hospital psychiatric consult service.4
  • In a prospective study of 50 patients treated with corticosteroids, 13 developed hypomania and 5 developed depression.5
Steroid-induced symptoms emerge from 3 to 4 days to a median of 11 days after a patient starts corticosteroid therapy. After steroids are discontinued, depressive symptoms persist approximately 4 weeks, mania 3 weeks, and delirium a few days. Approximately one-half of patients with steroid psychosis improve in 4 days and one-half within 2 weeks.2,6

Who is at risk?

Corticosteroids include the steroids produced in the adrenal gland (such as corticosterone) and their synthetic—and often more potent—analogues (such as prednisone).7 Because of their glucocorticoid, immunosuppressant, mineralocorticoid, and anti-inflammatory properties, steroids are used as replacement therapy and to treat a wide variety of illnesses (Table 1).

Table 1

Medical conditions for which corticosteroids are commonly used

DisorderIndications for corticosteroids
Acute adrenal insufficiencyAcute; replacement therapy
Addison’s diseaseChronic; replacement therapy
AsthmaAcute and chronic; anti-inflammatory
Inflammatory bowel diseaseAcute; anti-inflammatory
Multiple sclerosisAcute; exacerbations, immunosuppressant
Organ transplantChronic; immunosuppressant
Rheumatoid arthritisChronic; anti-inflammatory
Systemic lupus erythematosusAcute; severe exacerbation, immunosuppressant (high doses are used)
Age and gender. Patient age appears unrelated to development of psychiatric symptoms after corticosteroid use.2 One study suggested women are twice as likely as men to develop psychiatric symptoms (77 versus 38 cases in 115 patients),3 but many illnesses that require corticosteroid treatment occur more frequently in women. Other researchers found a slight female predominance (58% versus 42% of cases) when they excluded patients with systemic lupus erythematosus and rheumatoid arthritis, which are more common in women than in men.2

Dosage. Higher corticosteroid dosages increase the risk of psychiatric symptoms. In patients taking prednisone, the Boston Collaborative Drug Surveillance Project8 found the incidence of psychiatric side effects to be:

  • 1.3% in patients taking
  • 4.6% in those taking 41 to 80 mg
  • 18.4% in those taking >80 mg.
Psychiatric history. Past psychiatric illness does not seem to be a risk factor for psychiatric side effects of corticosteroids,9 although patients with a history of posttraumatic stress disorder are more likely to suffer depression while taking corticosteroids.10

Corticosteroid exposure. Patients who did not experience psychiatric side effects with corticosteroids in the past appear not to be protected if corticosteroids are used again. One report examined 17 cases of steroid-induced psychiatric illness in patients with previous exposure to corticosteroid therapy. Six patients had previous psychiatric side effects while taking corticosteroids, and 11 did not.2

Bipolar trigger?

Do corticosteroids’ acute psychiatric side effects have long-term sequelae? Longitudinal evidence is scarce, but a few reports suggest corticosteroids could play a role in the onset of primary bipolar I disorder:

  • A 28-year-old woman with no known mood symptoms before a short course of prednisone experienced six episodes of mania and depression when not taking corticosteroids during the subsequent 18 months.11
  • Among 16 patients with first-onset mood symptoms after corticosteroid use, a retrospective chart review found 7 had recurrent manic and depressive symptoms unrelated to additional corticosteroid use.12

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