Depression and Biologic Use in Arthritis: Chicken or Egg?
Among patients with inflammatory rheumatic diseases, the initiation of a biologic treatment or switching to another biologic was associated with an increased likelihood of the use of antidepressants and anxiolytics, Greek researchers found.
In a multivariate analysis that adjusted for age, sex, type of underlying disease, and concomitant treatment with glucocorticoids and conventional disease-modifying antirheumatic drugs (DMARDs), there was a positive association between starting treatment with a biologic agent and the use of antidepressants (OR 1.248, 95% CI 1.153-1.350, P<0.0001) or anxiolytics (OR 1.178, 95% CI 1.099-1.263, P<0.0001), according to Petros P. Sfikakis, MD, of the National and Kapodistrian University of Athens, and colleagues.
Similarly, there was a positive association between switching to a different biologic and the use of antidepressants (OR 1.502, 95% CI 1.370-1.646, P<0.0001) or anxiolytics (OR 1.161, 95% CI 1.067-1.264, P=0.001), the researchers reported online in RMD Open: Rheumatic & Musculoskeletal Diseases.
“The relationship between mood disorders and inflammation seems to be bi-directional, as chronic pain and inflammation are considered to be important mediators of depression, while at the same time depression affects perception of pain and reduces response to treatment, possibly by minimizing patient adherence to medication,” Sfikakis and co-authors explained.
Despite the recognized association between inflammation and depression or anxiety, little is known about the effects of initiation or switching biologics in patients with the inflammatory rheumatic diseases rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS).
To address this knowledge gap, the researchers conducted a retrospective study using nationwide data from the Greek Government Center for Social Security Services medical database, which covers almost 100% of the country’s population.
A total of 42,815 patients with inflammatory rheumatic diseases were registered in the database, with 18,925 being treated with conventional DMARDs alone, usually methotrexate. During the 2-year period of 2016 to 2018, 23,890 patients initiated or continued treatment with a biologic, which was usually a tumor necrosis factor (TNF) inhibitor, including 12,002 patients with RA, 5,465 with PsA, and 6,423 with AS.
More patients with PsA (18%) switched from one biologic to another compared with those with RA (13%) or AS (13.5%), and women more often switched than men in all disease subtypes (P>0.0001 for all):
Patients with PsA who switched were younger than nonswitchers (54.96 vs 56.20 years, P=0.007), were slightly younger in the RA group (63.06 vs 63.80, P=0.051), and were similar ages in the AS group (50.79 vs 51.24, P=0.351).
The use of antidepressants or anxiolytics, respectively, was reported in 24% and 43% of patients with RA, 19% and 36% of those with PsA, and 16% and 30% of those with AS.
After adjustment for age, sex, disease subtype, and concomitant medication use, the likelihood of using antidepressants was higher in patients with AS than in those with PsA (OR 1.130, 95% CI 1.031-1.238, P=0.009), while the likelihood was lower for those with RA (OR 0.880, 95% CI 0.821-0.943, P<0.0001).
In addition, compared with the PsA group, those with AS did not differ in their likelihood of receiving anxiolytic treatment, but RA patients were less likely to use these agents (OR 0.817, 95% CI 0.770-0.866, P<0.0001).
Sfikakis and co-authors offered several potential explanations for the relationship between the inflammatory arthritis and the use of mood stabilizing medications.
First, the pain and disability associated with these conditions can interfere with social functioning and employment, which can lead to depression. Moreover, the same proinflammatory cytokines implicated in these arthritides such as interleukins 1β and 6 and TNF have been detected in patients with major depression.
“It has been postulated that interferon-α, a potent cytokine inducer, triggers mood disorders by heightening right amygdala emotional reactivity. Conversely, treatment with anti-TNF agents has been shown to induce remission of underlying depression in the context of systemic autoimmune diseases, possibly by decreasing right amygdala reactivity,” the researchers wrote.
A further possibility is that depression itself could trigger or worsen inflammatory rheumatic diseases, with one recent study suggesting that psychological stress was commonly linked by RA patients with disease flares.
Another potential explanation is that depression may exacerbate patients’ perception of their disease state, showing higher scores on subjective disease activity ratings such as tender joint counts, fatigue, and patient global assessments.
The authors concluded that clinicians should consider the possibility of underlying depression or anxiety in patients who appear to be inadequately responding to their anti-arthritic medications when considering starting or switching a biologic.
A limitation of the study, the researchers said, was the lack of information about disease activity or severity in the national database.
Sfikakis and co-authors reported no competing interests.