Glucocorticoid exposure and initiation of SSRIs among patients with rheumatoid arthritis: A nested case-control study in UK primary care.

AIM: The immune system might affect the development of anxiety disorders, though mechanisms remain unclear. This nested case-control study investigates whether use of glucocorticoids, potent immunosuppressants, is associated with SSRI initiation (a proxy for pharmacologically treated mental disorders, predominantly depression and/or anxiety). METHODS: The study was nested within a cohort of primary care patients with a rheumatoid arthritis (RA) diagnosis between 1 January 2010 and 31 December 2019, commonly treated with glucocorticoids, from the UK Clinical Practice Research Datalink Aurum. RA patients receiving a first selective serotonin reuptake inhibitor (SSRI) prescription, the first-line treatment for anxiety disorders (cases), were matched on sex, year of birth, RA duration and GP practice to RA patients with no SSRI initiation (controls). Patients with prior depression diagnosis or antidepressant use were excluded. Associations between glucocorticoid exposure and SSRI initiation were estimated with conditional logistic regression, assessing timing, prednisone-equivalent cumulative dose and prescription count. RESULTS: From a cohort of 128 595 RA patients, 3134 cases and 4142 matched controls were identified. Recent (adjusted odds ratio 1.53, 95% CI 1.32-1.78) and past glucocorticoid exposure (adjusted odds ratio 1.40, 95% CI 1.07-1.83) were associated with a significantly increased SSRI initiation risk, regardless of cumulative dose or prescription count the year before the index date. CONCLUSION: Glucocorticoid exposure in RA patients was associated with increased odds of SSRI initiation. While residual confounding by disease severity cannot be excluded, clinicians should remain alert to mood symptoms during and after glucocorticoid therapy. Replication in other glucocorticoid-treated populations is warranted.