Corticosteroids are a component of many cancer treatment regimens. They prevent hypersensitivity reactions, reduce inflammation and tumour size, stimulate appetite and have anti-emetic and analgesic benefits. In addition, adjuvant steroids are a key part of chemotherapy for certain cancers (ie. haematological malignancies), significantly improving survival outcomes following treatment.¹ Unfortunately, corticosteroids have long been known to affect the mental state.² In this article we aim to give a brief overview of symptoms, risk factors and current treatment for steroid-induced mental disorder.

Hypomania, mania and psychosis are the most common psychiatric disorder associated with acute corticosteroids treatment.³ It has been reported that up to 6% of patients who were taking corticosteroids have severe psychotic episodes, while 28% experience mild-to-moderate reaction.⁴

Symptoms

Steroid-induced mental disorder represents a range of symptoms from mild (anxiety, euphoria, emotional lability, irritability, insomnia) to severe (mania, psychosis, severe depression).² Current evidence suggests mania is the most common psychiatric manifestation of steroid treatment.⁵  The Diagnostic and Statistical Manual of Mental Health Disorders, Fifth Edition, lists a number of criteria for the diagnosis of medication-induced bipolar and related disorders (see Table 1).⁶

A review on clinical profiles of case series shows that the affective profile includes mania (35%), depression (28%), delirium (13%), mixed affective state (12%) and psychosis (11%).⁷ The onset of psychiatric symptoms generally manifest within three to five days following commencement of steroids but have even been reported following completion of a steroid course.^8,9

 (click to enlarge)

Risk factors

The dose of corticosteroid appears to be the main risk factor for mental disorder. In 1972, the Boston Collaborative Drug Surveillance Program illustrated that in hospitalised patients (n = 676) taking prednisone, 18.4% of those who were on greater than 80mg/day experienced ‘severe psychiatric disturbance’. This compared with 4.6% who were receiving 40-80mg prednisone per day and 1.3% of those who were receiving less than 40mg prednisone per day.¹⁰ 

Risk of psychiatric symptoms after corticosteroid use does not appear to be associated with age and there is only a slight preponderance in females by comparison with males.³ A previous psychiatric history is not necessarily a risk factor for developing psychiatric adverse events secondary to corticosteroids.¹¹ However, heightened concern in cases with a history of bipolar disorder and prior steroid-induced mood disorder is clearly needed.¹²

Management

Currently, there is a lack of literature available on the treatment of steroid-induced mood disorder. To date, there are no available placebo-controlled trials investigating the efficacy of adjuvant psychotropic intervention for steroid-induced mood disorder in cancer patients. The current evidence is restricted to open-label trial, cohort study and case series, many of them in non-cancer medical patients. Reducing the dose of corticosteroid where possible is the first step although this is not always possible as it may disadvantage treatment outcome. Depending on the severity of the symptoms, psychopharmacological treatment may be necessary.¹³ 

Our practice is to discontinue antidepressants and to commence antipsychotic medication and/or a mood stabiliser, as such an approach is evidence-based in the management of bipolar mood disorders.^14,15,16 Most case series have reported a benefit from this approach. At present, there are no guidelines on preventative treatment for steroid-induced psychiatric disorder. Patients who have developed a moderate to severe psychiatric disorder following corticosteroid use and who require future steroid treatment should receive prophylactic treatment with an anti-psychotic or mood stabiliser.¹⁷

Psychiatric consultation and intervention

Patients with cancer are at increased risk of suicidal ideation and suicidal behaviour. It also has been shown that steroid treatment was associated with a seven-fold higher risk of suicide or suicide attempts.¹⁸ Early identification and treatment of steroid-induced mental disorder may reduce morbidity and mortality.¹⁹ The patients and their families should be educated regarding the risks of neuropsychiatric adverse effects associated with corticosteroid treatment so they can be more vigilant in identifying abnormal symptomatology and how to access help. Clinicians should have a low threshold for obtaining psychiatric specialty consultation in patients who at risk. 

An audit of steroid-induced mental disorder in CUH

Data was collected from consecutive referrals of adult cancer patients to the Liaison Psychiatry team in Cork University Hospital (CUH), Ireland from 2006-2014 (n = 1781). Steroid-induced mental disorder was the third most common diagnosis (7%, n = 124), following adjustment disorder (21%) and other mood disorders (12%). 

In the subgroup of those who were diagnosed with steroid-induced mood disorder (see Figure 1), the mean age was 58 years (standard deviation [SD] = 13) and there was no particular female preponderance (52%, n = 64 females). The most common cancer diagnosis was haematological malignancy (27%), followed by breast (18%), and lung and thoracic (18%). Medical oncology (42%), followed by radiation oncology (20%) and haematology (20%) were the most common referral sources. The most common reason for referral was irritability and/or aggression (28%) and anxiety and/or insomnia (28%). 

Treatments included reduced dose of steroid where possible, psycho-education on neuropsychiatric side effects of steroids, and psychotropic medication, typically antipsychotic medication (ie. olanzapine, quetiapine and haloperidol). 

 (click to enlarge)

Learning points

• Steroid-induced mood disorder can commonly present with mania, depression or mixed affective states

• High corticosteroid dose is the primary risk factor for steroid-induced mental disorder

• Clinicians should have a low threshold for obtaining psychiatric specialty consultation in patients who at risk 

• The main treatment of steroid-induced mood disorder is to reduce the corticosteroid, if possible, and to add in antipsychotic medication (olanzapine) or a mood stabiliser (sodium valproate, lithium).

 (click to enlarge)

References

1. Woolridge JE, Anderson CM, Perry MC. Corticosteroids in advanced cancer. Oncology 2001; 15: 225–236
2. Rome HP, Braceland FJ. Psychological response to corticotropin, cortisone, and related steroid substances; psychotic reaction types. J Am Med Assoc 1951; 145(1): 27-30
3. 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: 500-50
4. 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
5. Flores BH, Gumina HK. The Neuropsychiatric Sequelae of Steroid Treatment. November 3, 2003. Available from: http://www.dianafoundation.com/articles/df_04_article_01_steroids_pg01.html 
6. American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 5th ed. Washington: American Psychiatric Association, 2013
7. Sirois F. Steroid psychosis: a review. Gen Hosp Psychiatry 2003; 25: 27-33
8. Naber D, Sand P, Heigl B. Psychopathological and neuropsychological effects of 8-days’ corticosteroid treatment. A prospective study. Psychoneuroendocrinology 1996; 21(1): 25-31
9. Wolkowitz O, Rubinow D, Doran A et al. Prednisone effects on neurochemistry and behavior: preliminary findings. Arch Gen Psychiatry 1990; 47(10): 963-968
10. The Boston Collaborative Drug Surveillance Program. Acute adverse reactions to prednisone in relation to dosage. Clin Pharmacol Ther 1972; 13: 694-698
11. Patten SB, Neutel CI. Corticosteroid-induced adverse psychiatric effects: incidence, diagnosis and management. Drug Saf 2000; 22: 111-22
12. Vikram P, Krishan L. Stable bipolar patient switched to mania following clinical doses of prednisone. Case Reports in Psychiatry 2011; doi: 10.1155/2011/797658
13. Muzyk A, Hold S, Gagliardi J. Corticosteroid psychosis: stop therapy or add psychotropics? Curr Psychiatry 2010; 9: 61-63, 67-69
14. 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
15. Roxanas MG, Hunt GE. Rapid reversal of corticosteroid-induced mania with sodium valproate: A case series of 20 patients. Psychosomatics 2012; 53(6): 575-81
16. Falk WE, Mahnke MW, Poskanzer DC. Lithium prophylaxis of corticotropin-induced psychosis. JAMA 1979; 241: 1011-1012
17. Cerullo M. Corticosteroid-induced mania: Prepare for the unpredictable. Curr Psychiatry 2006; 5: 43-50
18. Lewis LJ, Pamela JS et al. Adverse consequences of glucocorticoid medication: psychological, cognitive, and behavioral effects. Am J Psychiatry 2014; 171(10): 1045-1051
19. Spoletini I, Gianni W, Caltagirone C et al. Suicide and cancer: where do we go from here? Crit Rev Oncol Hematol 2011; 78(3): 206-219