Med/Psych Update

Steroid-induced psychiatric symptoms: What you need to know

Current Psychiatry. 2021 April;20(4):33-38 | doi:10.12788/cp.0104

References

1. Dubovsky AN, Arvikar S, Stern TA, et al. The neuropsychiatric complications of glucocorticoid use: steroid psychosis revisited. Psychosomatics. 2012;53(2):103-115.
2. Roxanas MG, Hunt GE. Rapid reversal of corticosteroid-induced mania with sodium valproate: a case series of 20 patients. Psychosomatics. 2012;53(6):575-581.
3. Lewis DA, Smith RE. Steroid‐induced psychiatric syndromes. A report of 14 cases and a review of the literature. J Affect Disord. 1983;5(4):319-332.
4. Warren KN, Katakam J, Espiridion ED. Acute-onset mania in a patient with non-small cell lung cancer. Cureus. 2019;11(8):e5436.
5. Kenna HA, Poon AW, de los Angeles CP, et al. Psychiatric complications of treatment with corticosteroids: review with case report. Psychiatry Clin Neurosci. 2011;65(6):549-560.
6. Ling MH, Perry PJ, Tsuang MT. Side effects of corticosteroid therapy. Psychiatric aspects. Arch Gen. Psychiatry. 1981;38(4):471-477.
7. Ularntinon S, Tzuang D, Dahl G, et al. Concurrent treatment of steroid-related mood and psychotic symptoms with risperidone. Pediatrics. 2010;125(5):e1241-e1245.
8. Pokladinkova J, Meyboom RH, Vlcek J, et al. Intranasally administered corticosteroids and neuropsychiatric disturbances: a review of the international pharmacovigilance programme of the World Health Organization. Ann Allergy Asthma Immunol. 2008;101(1):67-73.
9. Walker EF, Trotman HD, Pearce BD, et al. Cortisol levels and risk for psychosis: initial findings from the North American prodrome longitudinal study. Biol Psychiatry. 2013;74(6):410-417.
10. Wolkowitz OM, Reus UI. Treatment of depression with antiglucocorticoid drugs. Psychosom Med. 1999;61(5):698-711.
11. Judd LL, Schettler PJ, Brown ES, et al. Adverse consequences of glucocorticoid medication: psychological, cognitive, and behavioral effects. Am J Psychiatry. 2014;171(10):1045-1051.
12. Appenzeller S, Cendes F, Costallat LT. Acute psychosis in systemic lupus erythematosus. Rheumatol Int. 2008;28(3):237-243.
13. Glynne-Jones R, Vernon CC, Bell G. Is steroid psychosis preventable by divided doses? Lancet. 1986;2(8520):1404.
14. Ismail MF, Lavelle C, Cassidy EM. Steroid-induced mental disorders in cancer patients: a systematic review. Future Oncol. 2017;13(29):2719-2731.
15. Magariños AM, McEwen BS. Stress-induced atrophy of apical dendrites of hippocampal CA3c neurons: involvement of glucocorticoid secretion and excitatory amino acid receptors. Neuroscience. 1995;69(1):89-98.
16. Brown BS, Stuard G, Liggin JDM, et al. Effect of phenytoin on mood and declarative memory during prescription corticosteroid therapy. Biol Psychiatry. 2005;57(5):543-548.
17. Desai S, Khanani S, Shad MU, et al. Attenutation of amygdala atrophy with lamotrigine in patients receiving corticosteroid therapy. J Clin Psychopharmacol. 2009;29(3):284-287.
18. Gable M, Depry D. Sustained corticosteroid-induced mania and psychosis despite cessation: a case study and brief literature review. Int J Psychiatry Med. 2015;50(4):398-404.

Young children (age <6) and older adults appear to be at greater risk for cognitive and memory disturbances from steroid use.¹⁰ In addition, patients have individual levels of susceptibility to steroid-induced psychiatric symptoms that can vary over time. The risk for adverse effects may be elevated based on response to previous courses of glucocorticoid treatment.¹⁰ While gender, age, dosage, and duration of treatment influence risk, it is not possible to predict which patients will experience psychiatric effects during a given course of glucocorticoid therapy. Therefore, all patients should be considered to have the potential of developing such effects, and should be monitored during glucocorticoid treatment and withdrawal.

Goals for future research

To help reduce the severity of and cost associated with steroid-induced psychiatric symptoms,^5,14 future studies should focus on controlled trials of preventative strategies. In particular, recent advances in genetic mapping may help identify involvement of certain genes or polymorphisms.⁵ Because current guidelines for the prevention and treatment of steroid-induced psychiatric symptoms are not evidence-based, controlled clinical trials are needed to elucidate the optimal management of such symptoms. There is much interplay between many of the proposed mechanisms of steroid-induced psychiatric symptoms, and future studies can help uncover a deeper understanding of the intricacies of this phenomenon.

CASE CONTINUED

Mrs. N is admitted for altered mental status. Medical workup includes MRI of the brain, MRI of the neck, cardiac echocardiogram, and EEG. There is no evidence of acute structural pathology. She is started on olanzapine, 10 mg/d at bedtime for manic and psychotic symptoms, and is discharged after 5 days. After 1 month, the outpatient psychiatrist gradually decreases and discontinues olanzapine as Mrs. N steadily returns to baseline. One year after discharge, Mrs. N continues to report resolution of her manic and psychotic symptoms.

Bottom Line

Steroids can induce a wide range of psychiatric symptoms, including mania/ hypomania, anxiety, and depression. Initial treatment typically includes tapering or discontinuing the steroid when possible. Other proposed treatments include certain antipsychotics, antidepressants, and other psychotropics, but the supporting evidence is largely anecdotal or based on case studies. Additional research is needed to elucidate the mechanism and treatment recommendations.

Related Resources

Janes M, Kuster S, Goldson TM, et al. Steroid-induced psychosis. Proc (Bayl Univ Med Cent). 2019;32(4):614-615.
Mayo Clinic. Prednisone and other corticosteroids. https://www.mayoclinic.org/steroids/art-20045692

Drug Brand Names

Haloperidol • Haldol
Lamotrigine • Lamictal
Lithium • Eskalith, Lithobid
Methylprednisolone injection • Solu-Medrol
Olanzapine • Zyprexa
Paroxetine • Paxil
Phenytoin • Dilantin
Quetiapine • Seroquel
Risperidone • Risperdal
Sertraline • Zoloft
Valproate • Depakote