Glucocorticoid Drugs Associated With Neuropsychiatric Illnesses, Suicide |PharmD India

Glucocorticoids are important neuromodulating hormones, and the authors of the current study describe the background of how glucocorticoids might affect the risk for neuropsychiatric disorders. Mood disorders are associated with dysfunction in negative feedback loops of endogenous (natural) glucocorticoids, and the risk for depression among patients with Cushing's disease is 50% to 80%. An estimated 10% of these patients experience psychosis or mania.

Estimates of the prevalence of neuropsychiatric disorders related to the exogenous administration of glucocorticoids vary widely, from less than 1% to 50%. It does appear that higher doses of glucocorticoids are more likely to promote neuropsychiatric disorders, but other details of the relationship between glucocorticoids and neuropsychiatric disorders remain unclear.

STUDY SYNOPSIS AND PERSPECTIVE

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, 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.

"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.

This study was published online February 17 in the American Journal of Psychiatry. CLICK HERE

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.

Condition	HR	95% CI
Suicidal behaviors	6.89	4.52 - 10.50
Delirium/confusion	5.14	4.54 - 5.82
Mania	4.35	3.67 - 5.16
Depression	1.83	1.72 - 1.94
Panic disorder	1.45	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."

CLINICAL IMPLICATIONS

Mood disorders are associated with dysfunction in negative feedback loops of endogenous glucocorticoids, and the risk for depression among patients with Cushing's disease is 50% to 80%. An estimated 10% of these patients experience psychosis or mania. Higher doses of exogenous glucocorticoids are more likely to promote neuropsychiatric disorders.

The current study by Fardet suggests that treatment with glucocorticoids can increase the risk for a number of neuropsychiatric diagnoses, along with the risk for suicide attempt or completed suicide. A history of neuropsychiatric disorders and larger daily doses of glucocorticoids predicted a higher risk for all incident outcomes, and a prior episode of glucocorticoid-induced neuropsychiatric disorder increased the risk for a subsequent episode.

Source: Medscape

Akshaya Srikanth

Pharm.D Resident

Hyderabad, India