Objectives Depression and anxiety are linked bi-directionally with inflammatory rheumatic diseases (IRDs) activity, which in turn, depends on subjective patient reported outcomes that can be distorted by comorbid mood disorders. We tested the hypothesis that introduction and/or switching of biologic agents for IRDs are associated with treatment for depression and/or anxiety, by analysing real-world data. Methods Using a country-wide electronic prescription database (10 012 604 registered, 99% population coverage), we captured almost all patients with rheumatoid arthritis (n=12 002), psoriatic arthritis (n=5465) and ankylosing spondylitis (n=6423) who received biologic disease modifying anti-rheumatic drugs (bDMARDs) during a 2-year period (8/2016-7/2018). Concomitant antidepressant/anxiolytic medication use was documented in patients who started or switched bDMARDs and compared with those who remained on conventional synthetic (cs)DMARDs or the same bDMARD, respectively, by multivariate regression analysis. Results Two-year data analysis on 42 815 patients revealed that bDMARD introduction was associated with both antidepressant [OR: 1.248, 95% CI 1.153 to 1.350, p<0.0001] and anxiolytic medication use [OR: 1.178, 95% CI 1.099 to 1.263, p<0.0001]. Moreover, bDMARD switching was also associated with antidepressant [OR: 1.502, 95% CI 1.370 to 1.646, p<0.0001] and anxiolytic medication use [OR: 1.161, 95% CI 1.067 to 1.264, p=0.001]. Notably, all these associations were independent of age, gender, underlying disease diagnosis and concomitant glucocorticoid or csDMARD medication use. Conclusion In real-world settings, both introduction and switching of bDMARDs in patients with IRDs were associated with the presence of mood disorders. Although a causal relationship is uncertain, the impact of depression and anxiety should always be considered by physicians facing the decision to introduce or switch bDMARDs in patients with active IRDs.