Rheumatoid Arthritis and Depression: A Strengthening Relationship  

A new study further reinforces the connection between rheumatoid arthritis (RA) and depression and anxiety, as well as the need for a corresponding connection between rheumatology and mental health. Meanwhile, interest is growing in the ability of anti-inflammatory drugs to address both conditions. A recent report published in the Annals of the Rheumatic Diseases analyzed data from 848 newly diagnosed RA patients and found higher depression and anxiety rates at the time of diagnosis compared with the 1-year mark.

At baseline, frequency of anxiety and depression was 19.0% and 12.2%, respectively, with a reduction at month 12 to 13.4% and 8.2%. Changes in RA disease activity scores correlated with changes in depression and anxiety scores at months 6. "Depression and anxiety are recognized comorbidities in the context of rheumatoid arthritis. However, solid data examining the possible association of RA with depression/anxiety in an early, real-world RA cohort are limited," wrote study co-author George Fragoulis, MD, a rheumatologist at the University of Glasgow in Scotland, in an emailed response to questions. "We sought to investigate the frequency of anxiety and depression in patients with early RA over time."

Multivariable analysis indicated that anxiety scores at baseline were associated with various factors including female gender, younger age and patient global assessment scores. At months 6 and 12, anxiety scores were associated with low body mass index), patient global assessment scores, and baseline anxiety scores. In depression, analysis indicated a connection with patient global assessment scores at baseline and at months 6 and 12. Depression also was associated with levels of the inflammation marker C-reactive protein, baseline depression scores and baseline anxiety scores. "Importantly, C-reactive protein levels were highly correlated with depression, but not with anxiety scores, at different time points," Fragoulis wrote.

Clinical Implications

The often self-perpetuating relationship between RA and depression and anxiety is well established. Physical limitations imposed by RA, for example, can worsen depression and symptoms such as fatigue. In addition, some RA treatments can play a role. Systemic corticosteroids such as prednisone and bethamethasone can cause mood swings and exacerbate depression or anxiety. "Some treatments of rheumatoid arthritis may be associated with depression," said Paul Holtzheimer, MD, a psychiatrist with Dartmouth Hitchcock Medical Center in New Hampshire. "Prednisone has significant psychological risks. Most rheumatologists know this, that it's not just the rheumatoid arthritis but the treatment." Despite widespread awareness, effective clinical management has at times remained elusive.

A 2013 study found that while 13% of RA physician visits involved a comorbid diagnosis of depression, only 1% of visits included a depression screening. Experts recommended rheumatologists take advantage of the PHQ-9, a freely available and easy-to-use depression assessment tool. "Pretty much anybody coming into the primary care or rheumatology office should be screened for depression," said Holtzheimer. "The diagnosis is not hard to make." Given the prevalence of depression and anxiety in RA patients, rheumatologists should have working knowledge of depression and a local network of mental health professionals. "A rheumatologist should be able to recognize the relevant symptomatology and treat or make a referral to psychiatrists or mental health services, where appropriate," Fragoulis wrote. "Given the results from our and other studies supporting the bidirectional relation between arthritis and depression, it is important to highlight the need for global treatment. In other words, we should be treating not only arthritis but its comorbidities as well. From that point of view, a multidisciplinary approach is essential."

According to experts, rheumatologists or primary care physicians can recommend or prescribe initial depression treatments, such as psychotherapy or drugs like sertraline or paroxetine, before referring the patient elsewhere. "The degree to which rheumatologists want to treat [depression or anxiety] is based on their choice," Holtzheimer said. "We don't recommend a referral to a psychiatrist until they are not responding to first-line therapy, including medication and psychotherapy." In the longer term, researchers are diving deeper into the underlying biology of this extremely complex relationship. A fairly robust body of evidence indicates that inflammation, such as that caused by RA, causes depression. While systemic corticosteroids can aggravate depression, common anti-inflammatory drugs are increasingly shown to be effective in treating depression as well as RA. Nonsteroidal anti-inflammatory drugs and cytokine inhibitors have shown in studiesthey can positively impact depression. The anti-inflammatory drug class known as COX-2 inhibitors also have shown promise. Studies indicate that COX-2 inhibitors like celecoxib are valuable add-ons to antidepressants when compared with a placebo. "Because of the connection, people have looked at things from aspirin to ibuprofen, which might have subtle antidepressant effects," Holtzheimer said. "Inflammation is driven by cytokines, specifically interleukins. The subtleties of inflammation response are something that's gaining a lot of traction." 


Reference:  Annals of Rheumatic Diseases 16 JUNE 2018 RA:Depression and anxiety in an early rheumatoid arthritis by. G.Fragoulis and J. Cavanagh et al.