Rapid reversal of corticosteroid-induced mania with sodium valproate: a case series of 20 patients

Psychosomatics. 2012 Nov-Dec;53(6):575-81. doi: 10.1016/j.psym.2012.06.006.


Background: Glucocorticoids are widely used in medicine and are known to cause psychiatric side effects, including mania. There is anecdotal evidence that sodium valproate is effective for treating psychiatric side effects of glucocorticoids.

Objective: To describe a case series of 20 patients receiving corticosteroids for various medical conditions who developed manic-like symptoms. They were treated with sodium valproate while continuing on corticosteroids.

Method: Patients treated with corticosteroids who reported to their physician subjective distress or who were openly disruptive in the ward were assessed by a consultation-liaison psychiatrist on the same day with the Young Mania Rating Scale. Immediately afterwards, blood was taken to measure the cortisol or dexamethasone level and then started on sodium valproate 500 mg twice daily. Valproate levels were measured on day 3 to adjust the dose.

Results: There was a significant, rapid improvement of symptoms within 48 hours after sodium valproate was initiated. Within 72 hours all patients were euthymic and remained so over the ensuing week. The only major side effect was hyperammonemia in 1 case which resolved when valproate was stopped.

Conclusions: This case series shows that sodium valproate is a safe medication that rapidly reverses manic-like symptoms within a few days without needing to stop the corticosteroids, thus allowing the medical treatment to continue. The ability to continue treatment while controlling or ameliorating the psychiatric side effects of glucocorticoids with sodium valproate is an advance over previous approaches. The mechanism of this rapid action is unclear and deserves further study.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Analysis of Variance
  • Antimanic Agents / administration & dosage
  • Antimanic Agents / blood
  • Antimanic Agents / therapeutic use*
  • Bipolar Disorder / blood
  • Bipolar Disorder / chemically induced
  • Bipolar Disorder / drug therapy*
  • Dexamethasone / blood
  • Female
  • Glucocorticoids / administration & dosage
  • Glucocorticoids / adverse effects*
  • Glucocorticoids / blood
  • Humans
  • Hydrocortisone / blood
  • Hyperammonemia / chemically induced
  • Immunoassay / methods
  • Luminescent Measurements
  • Male
  • Middle Aged
  • Prospective Studies
  • Psychiatric Status Rating Scales / statistics & numerical data
  • Treatment Outcome
  • Valproic Acid / administration & dosage
  • Valproic Acid / blood
  • Valproic Acid / therapeutic use*
  • Young Adult


  • Antimanic Agents
  • Glucocorticoids
  • Valproic Acid
  • Dexamethasone
  • Hydrocortisone