Neuropsychiatric Side Effects of Glucocorticoid Use Are Common in Patients

Depression and mania are the most common neuropsychiatric side effects of glucocorticoid use among patients, according to study findings published in The Journal of Clinical Endocrinology & Metabolism.

While glucocorticoids are commonly used in a wide range of diseases, they have the potential to cause severe side effects like neuropsychiatric adverse events. Researchers conducted a systematic review and meta-analysis to assess the neuropsychiatric effects of glucocorticoids and to estimate the proportion of patients experiencing these side effects.

The researchers collected data from PubMed, Embase, Web of Science, Cochrane Library, PsycINFO, and Academic Search Premier. The researchers determined the risk of bias using the Cochrane risk-of-bias tool and the risk of bias in nonrandomized studies of interventions (ROBINS-I) assessment tool.

Eligible participants were enrolled in studies that collected information regarding psychiatric side effects while or after taking glucocorticoids. Studies were required to use validated questionnaires to investigate side effects. Some exclusion criteria were patients taking glucocorticoids as an endocrine replacement and if glucocorticoids were used to treat psychiatric effects.

The primary outcome was the proportion of neuropsychiatric effects among patients taking glucocorticoids measured using validated questionnaires.

Out of the 3987 eligible studies identified, a total of 49 studies were selected, including 6 randomized controlled trials (RCTs), 12 cross-sectional studies, and 31 cohort studies. A total of 39 different questionnaires were used to assess neuropsychiatric events.

Of the 49 studies, 39 were conducted in an adult population and 10 were conducted in children.

The most researched glucocorticoids were prednisolone (n=15), dexamethasone (n=5) and methylprednisolone (n=4). The duration and dosages of glucocorticoids varied per study.

The researchers conducted a meta-analysis of 11 studies with 1340 patients to determine the proportion of depression in patients taking glucocorticoids. Compared to individuals who did not use glucocorticoids, those who used them had higher scores on the depression questionnaires, with higher scores indicating worse symptoms (standardized mean difference [SMD], 0.80; 95% CI, 0.35-1.26).

Of the 14 studies including 455 patients assessing mania, the researchers found that compared to patients who do did not use glucocorticoids, those who did use them had higher scores on the mania questionnaires (SMD, 0.78; 95% CI 0.14-1.42). Higher scores on these scales indicated worse symptoms.

Among the 4 studies (n=9170 patients) that investigated anxiety among patients who took glucocorticoids, the proportion of those who developed anxiety was 8% (95% CI, 2%-25%; I²,72%).

The 6 studies (n=1101 patients) that evaluated delirium in patients taking glucocorticoids showed a pooled proportion of 16% (95% CI, 6%-36%; I², 97%).  A meta-analysis of 3 studies showed that there was no association between glucocorticoid use and delirium (odds ratio [OR], 0.80; 95% CI 0.30-2.12).

Study limitations are heterogeneity among patients and study characteristics, differences in data reporting, and only a few studies included in the final analysis.

“[I]t is important to acknowledge the potential of glucocorticoids to impact the brain and induce neuropsychiatric adverse effects given its use by a substantial proportion of the population,” the researchers concluded. “Upon starting glucocorticoid treatment, awareness of possible psychiatric side effects is essential.”