Glucocorticoids Linked to Suicide, Neuropsychiatric Disorders

Deborah Brauser

March 01, 2012

March 1, 2012 — Glucocorticoid medications given in primary care settings are associated with suicidal behaviors and severe neuropsychiatric disorders, new research suggests.

In a large, population-based study of adult patients in the United Kingdom (UK), those receiving glucocorticoids were almost 7 times more likely to commit or attempt suicide, more than 5 times more likely to develop delirium, more than 4 times more likely to develop mania, and almost twice as likely to develop depression than those with the same underlying conditions who did not receive the medications.

In addition, patients younger than 30 years were at particular risk for suicide attempts, women were more at risk for depression, and men were at especially increased risk for mania and delirium/confusion/disorientation. Higher dosages of the medications were also linked to an overall greater risk for adverse outcomes.

"Steroid-treated patients do not always know that the neuropsychiatric symptoms that they are experiencing are induced by the treatment. They may, for instance, think that they are induced by the underlying disease," lead author Laurence Fardet, MD, PhD, from the Department of Internal Medicine at Saint-Antoine Hospital in Paris, France, told Medscape Medical News.

"Therefore, I believe that physicians must be aware that these neuropsychiatric adverse events are frequent and potentially life-threatening in order to better inform the patient and their family, and to avoid steroids when possible," said Dr. Fardet.

With data for almost 3500 glucocorticoid-treated patients included, the investigators note that this is the largest trial to date to examine these adverse outcomes.

The study was published online February 17 in the American Journal of Psychiatry.

Commonly Prescribed

Glucocorticoid medications have anti-inflammatory properties and are commonly used to treat asthma, rheumatoid arthritis, and other autoimmune diseases and to prevent transplant rejection. Although corticosteroids actually refer to both glucocorticoids and mineralocorticoids, the first 2 terms are often used interchangeably.

According to the researchers, natural glucocorticoids, which include cortisol, affect mood, behavior, and other central nervous system–related processes.

In addition, a link between synthetic glucocorticoids and depressive and manic syndromes "is relatively well documented," the investigators note.

"In view of the frequency and severity of such disturbances in various clinical populations who received prescriptions for glucocorticoids, there is a need for population-based prevalence studies," they write.

Dr. Fardet reported that he has been involved in studies examining the epidemiology of glucocorticoid-induced adverse events for about 10 years.

"While many people in the general population, about 1%, are receiving glucocorticoids at any point of time, some of their adverse events are quite unwell described in the medical literature," he said.

For this study, the investigators evaluated data from The Health Improvement Network (THIN) on all patients older than 18 years who visited UK general practices between 1990 and 2008. The study included 372,696 patients who were prescribed at least 1 glucocorticoid (mean age, 57.5 years; 59.1% women; 24% with a history of a neuropsychiatric disorder).

Cases of neuropsychiatric outcomes are coded for all patients in the THIN database.

Awareness Needed

Results showed that 786,868 courses of oral glucocorticoids were prescribed for the patient population. A total of 90 cases of attempted suicides, 19 cases of completed suicides, and 10,220 cases of severe neuropsychiatric outcomes were reported.

"The incidence of any of these outcomes was 22.2 per 100 person-years at risk for first-course treatments," report the investigators.

The adjusted hazard ratios (HRs) for the various adverse outcomes in those prescribed glucocorticoids compared with the patients who were not are shown below.



95% CI

Suicidal behaviors


4.52 - 10.50



4.54 - 5.82



3.67 - 5.16



1.72 - 1.94

Panic disorder


1.15 - 1.85

HR = hazard ratio; CI = confidence interval

Other significant risk factors for all adverse outcomes were large daily doses of the medications and a history of disorders. Interestingly, a lower risk was associated with prior treatment with glucocorticoids.

When examining specific subgroups, investigators found that women treated with the drug class were at a significantly higher risk for depression than the men who were treated, but that the men were at a higher risk for mania and delirium/confusion/disorientation.

The older the treated patient, the higher the risk was for mania, depression, and delirium/confusion/disorientation. However, younger patients who were treated (those between the ages of 18 and 30 years) were at higher risk for suicidal behaviors.

"Educating patients and their families about these adverse events and increasing primary care physicians' awareness about their occurrence should facilitate early monitoring," write the investigators.

They add that caution is needed when administering this drug type, "in particular when the reasons for prescribing are not in accordance with the consensual clinical recommendations."

New Take on Old Problem

"I thought this was a new take on an old problem of the effect of prescription corticosteroids on the brain," E. Sherwood Brown, MD, PhD, professor of psychiatry and director of the Psychoneuroendocrine Research Program at the University of Texas Southwestern Medical Center in Dallas, told Medscape Medical News.

Dr. E. Sherwood Brown

"The thing that makes this study different from others is its huge sample size, including about 1.2 million controls. So they were able to get an epidemiological perspective on something that's largely been looked at through case reports and case series over the last 60 years," said Dr. Brown, who was not involved with this research.

He added that although "a lot of it was what we'd expect" on the basis of past studies in terms of the increased risk for depression and mania in those treated with glucocorticoids, the finding of increased risk for delirium was relatively new.

"It's known in the field that there are changes in memory and other cognitive domains with corticosteroids. But no one has really focused on that very much. Here, it had a higher risk than for depression or mania, especially in older patients. And I think that's a new population to think about with these medicines."

Dr. Brown noted that there have been past reports of suicidal behaviors with these medications, "but this quantifies that with much bigger numbers." However, because the number of actual completed suicides reported was very low, he said that caution should be used in interpreting that finding.

In addition, he pointed out that the study showed that the rate of psychiatric referral was not significantly increased for those exposed to glucocorticoids compared with those who were not exposed.

"I don't know if one interprets that as physicians are well aware of these effects and therefore don't see a need for a psychiatric referral or whether they aren't referring because they aren't that aware of these effects," said Dr. Brown.

Overall, he said that even with their adverse outcomes, these medications are just too important to not prescribe.

"You certainly can't stop using them because they really are lifesaving for some people. So I think the take-home message is an awareness that they have both mood and cognitive side effects, particularly when treating patients with high doses of the medications," he concluded.

The study was supported by grants from the French National Society of Internal Medicine and the Public Assistance–Paris Hospitals, and from the UK Medical Research Council. The study authors and Dr. Brown have disclosed no relevant financial relationships.

AJP in Advance. Published online February 17, 2012. Abstract


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