Glucocorticoid withdrawal syndrome: Disproportionality analysis of cases using VigiBase data.

Background: Glucocorticoids are associated with withdrawal syndrome, but specific glucocorticoid types that cause severe conditions remain unclear.

Objectives: This study identified glucocorticoids that exhibit significant pharmacovigilance signals for withdrawal, directly comparing the different types to determine those that exhibit a higher risk. We also aimed to investigate the routes of administration for glucocorticoids that are most likely to cause glucocorticoid withdrawal syndrome (GWS) and identify the age, sex, and regional groups among which GWS is more common.

Methods: We extracted the region, severity, age group, sex, and indications from VigiBase reports on GWS from January 2013 to December 2023.

Results: Among 343,296 adverse drug reactions, 1,713 were withdrawal syndrome, with a higher prevalence among females (60%). Prednisone accounted for 28% of the cases, followed by hydrocortisone (17%) and betamethasone (14%). Case numbers tended to peak in 2021, with the highest incidence between ages 18-44 (36%) and significant regional variations for different glucocorticoids. Most cases (77%) were serious, with 18% requiring prolonged hospitalization. Predominant administration routes were topical for betamethasone, triamcinolone, and hydrocortisone; oral for prednisone and prednisolone; and intravenous for methylprednisolone. Disproportionality signals indicated that hydrocortisone exhibited the highest association with GWS (reporting odds ratio [ROR]: 4.04, 95% confidence interval [CI]: 3.59-4.53), followed by betamethasone (ROR: 3.81, 95% CI: 3.35-4.32), triamcinolone (ROR: 2.15, 95% CI: 1.83-2.52), and cortisone (ROR: 1.57, 95% CI: 0.99-2.50).

Conclusion: Abrupt withdrawal of glucocorticoid therapy may cause GWS. Healthcare providers should inform patients about the potential risks of withdrawal, particularly when prescribing topical hydrocortisone and betamethasone, topical and nasal triamcinolone, and oral and topical cortisone, to promote safer practices.