Med/Psych Update

Corticosteroid psychosis: Stop therapy or add psychotropics?

Current Psychiatry. 2010 January;9(1):61-68

References

1. Lewis DA, Smith RE. Steroid-induced psychiatric syndromes: a report of 14 cases and a review of the literature. J Affect Disord. 1983;5:319-332.

2. Bolanos SH, Khan DA, Hanczyc M, et al. Assessment of mood states in patients receiving long-term corticosteroid therapy and in controls with patient-rated and clinician-rated scales. Ann Allergy Asthma Immunol. 2004;92:500-505.

3. Warrington TP, Bostwick JM. Psychiatric adverse effect of corticosteroids. Mayo Clin Proc. 2006;81(10):1361-1367.

4. Sirois F. Steroid psychosis: a review. Gen Hosp Psychiatry. 2003;25:27-33.

5. Newcomer JW, Craft S, Hershey T, et al. Glucocorticoid-induced impairments in declarative memory performance in adult humans. J Neurosci. 1991;14:2047-2053.

6. Hall RC, Popkin MK, Stickney SK, et al. Presentation of the steroid induced psychosis. J Nerv Ment Dis. 1979;167:229-236.

7. The Boston Collaborative Drug Surveillance Program. Acute adverse reactions to prednisone in relation to dosage. Clin Pharmacol Ther. 1972;13:694-698.

8. Brown ES, Chamberlain W, Dhanani N, et al. An open-label trial of olanzapine for corticosteroid-induced mood symptoms. J Affect Disord. 2004;83:277-281.

9. Falk WE, Mahnke MW, Poskanzer DC. Lithium prophylaxis of corticotropin-induced psychosis. JAMA. 1979;241:1011-1012.

10. Brown ES, Stuard G, Liggin JD, et al. Effect of phenytoin on mood and declarative memory during prescription corticosteroid therapy. Bio Psychiatry. 2005;57:543-548.

11. Brown ES, Frol AB, Khan DA, et al. Impact of levetiracetam on mood and cognition during prednisone therapy. Eur Psychiatry. 2007;22:448-452.

12. Brown ES, Frol A, Bobadilla L, et al. Effect of lamotrigine on mood and cognition in patients receiving chronic exogenous corticosteroids. Psychosomatics. 2003;44(3):204-208.

13. Goldman LS, Goveas J. Olanzapine treatment of corticosteroid-induced mood disorders. Psychosomatics. 2002;43(6):495-497.

14. Brown ES, Khan DA, Suppes T. Treatment of corticosteroid-induced mood changes with olanzapine. Am J Psychiatry. 1999;156(6):968.-

15. Budur K, Pozuelo L. Olanzapine for corticosteroid-induced mood disorders. Psychosomatics. 2003;44(4):353.-

16. Herguner S, Bilge I, Yavuz Yilmaz A, et al. Steroid-induced psychosis in an adolescent: treatment and prophylaxis with risperidone. Turk J Pediatr. 2006;48:244-247.

17. DeSilva CC, Nurse MC, Vokey K. Steroid-induced psychosis treated with risperidone. Can J Psychiatry. 2002;47:388-389.

18. Kato O, Misawa H. Steroid-induced psychosis treated with valproic acid and risperidone in a patient with systemic lupus erythematosus. Prim Care Companion J Clin Psychiatry. 2005;7(6):312.-

19. Kramer TM, Cottingham EM. Risperidone in the treatment of steroid-induced psychosis. J Child Adolec Psychopharmacol. 1999;9:315-316.

20. Siddiqui Z, Ramaswamy S, Petty F. Quetiapine therapy for coricosteroid-induced mania. Can J Psychiatry. 2005;50(1):77-78.

21. Naber D, Sand P, Heigl B. Psychopathological and neuropsychological effects of 8-days’ corticosteroid treatment. A prospective study. Psychoneuroendocrinology. 1996;21(1):25-31.

22. Brown ES, Woolston DJ, Frol A, et al. Hippocampal volume, spectroscopy, cognition, and mood in patients receiving corticosteroid therapy. Biol Psychiatry. 2004;55:538-545.

23. Schatzberg AF, Rothschild AJ, Langlais PJ, et al. A corticosteroid/dopamine hypothesis for psychotic depression and related states. J Psychiat Res. 1985;19(1):57-64.

24. Sabet-Sharghi F, Hutzler JC. Prophylaxis of steroid-induced psychiatric syndromes. Psychosomatics. 1990;31(1):113-114.

25. Siegal FP. Lithium for steroid-induced psychosis. N Engl J Med. 1978;299(3):155-156.

26. Goggans FC, Weisberg LJ, Koran LM. Lithium prophylaxis of prednisone psychosis: a case report. J Clin Psychiatry. 1983;44(3):111-112.

27. Merrill W. Case 35-1998: use of lithium to prevent corticosteroid-induced mania. N Engl J Med. 1999;340(14):1123.-

28. Himelhoch S, Haller E. Extreme mood lability associated with systemic lupus erythematosus and stroke successfully treated with valproic acid. J Clin Psychopharmacol. 1996;16(6):469-470.

29. Kahn D, Stevenson E, Douglas CJ. Effect of sodium valproate in three patients with organic brain syndromes. Am J Psychiatry. 1998;145(8):1010-1011.

30. Abbas A, Styra R. Valproate prophylaxis against steroid induced psychosis. Can J Psychiatry. 1994;39(3):188-189.

31. Preda A, Fazeli A, McKay BG, et al. Lamotrigine as prophylaxis against steroid-induced mania. J Clin Psychiatry. 1999;60(10):708-709.

32. Ginsberg DL, Sussman N. Gabapentin as prophylaxis against corticosteroid-induced mania. Can J Psychiatry. 2001;44:455-456.

33. Wada K, Yamada N, Yamauchi Y, et al. Carbamazepine treatment of corticosteroid-induced mood disorder. J Affect Disord. 2001;65:315-317.

34. Saklad S. Management of corticosteroid-induced psychosis with lithium. Clin Pharm. 1987;6(3):186.-

Box

Pathophysiology of corticosteroid-induced psychosis

How corticosteroids cause psychosis is not well understood. One theory suggests that corticosteroids act at steroid-specific receptors and suppress filtering by the hippocampus of irrelevant stimuli.²¹

Supporting this theory of hippocampal change, a study of 17 patients receiving corticosteroid therapy for >6 months found decreased hippocampal volume compared with a control group.²² Other possible causes include suppressed hypothalamus-pituitary axis and enhanced dopamine neurotransmission.²³

Consider adding a low-dose atypical antipsychotic with which case studies report quick symptom resolution and patients tolerating these agents. Monitor carefully for metabolic changes, a risk associated with antipsychotics and corticosteroids. Lithium would be a good second-line therapy because of its demonstrated benefit for both prophylaxis and treatment of psychiatric disturbances.

Clinical Point

Consider adding a low-dose atypical antipsychotic to corticosteroid therapy; lithium may be second-line with precautions

Lithium use can be complicated and dangerous in patients who have underlying diseases associated with renal dysfunction, however—such as nephrotic syndromes and SLE—leading some authors to suggest valproic acid or carbamazepine instead.³³ In addition, corticosteroid-induced changes in sodium balance could increase the risk of lithium toxicity.³⁴

When patients cannot tolerate atypical antipsychotics or lithium, case reports support the use of valproic acid, carbamazepine, lamotrigine, or gabapentin to treat symptoms of corticosteroid-induced psychosis.

Related resources

Cerullo MA. Expect psychiatric side effects from corticosteroid use in the elderly. Geriatrics. 2008;63(1):15-18.
Sirois F. Steroid psychosis: a review. Gen Hosp Psychiatry. 2003;25:27-33.
Patten SB, Neutel CI. Corticosteroid-induced adverse psychiatric effects: incidence, diagnosis, and management. Drug Safety. 2000;22(2):111-122.
Warrington TP, Bostwick JM. Psychiatric adverse effects of corticosteroids. Mayo Clin Proc. 2006;81(10):1361-1367.

Drug brand names

Aripiprazole • Abilify
Carbamazepine • Tegretol
Corticotropin • Acthar
Gabapentin • Neurontin
Lamotrigine • Lamictal
Levetiracetam • Keppra
Lithium • Lithobid, Eskalith, others
Methylprednisolone • Medrol
Olanzapine • Zyprexa
Phenytoin • Dilantin
Prednisone • Deltasone
Quetiapine • Seroquel
Risperidone • Risperdal
Valproic acid • Depakene
Ziprasidone • Geodon

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.