The Bidirectional Relationship Between Depression and Rheumatoid Arthritis


Depression affects up to 17% of patients with rheumatoid arthritis, but not all patients are assessed for their mental well-being.

Although rheumatoid arthritis (RA) only affects 1% of adults in most countries, up to 17% of these patients have a major depressive disorder (MDD). However, not all patients are assessed for their mental well-being even though detecting and managing depression could optimize the care of patients with RA, according to a review published in Rheumatology and Therapy.

Not only is depression 2 times more common in patients with RA than in the general population, but studies have shown there is a bidirectional relationship: the chronic inflammation impairs effective coping behaviors to stress, which results in depression that in turns leads to worse long-term outcomes.

“In RA, quality of life (QoL) is significantly decreased because of pain, fatigue, and disability, causing mood change in the form of anxiety and depression,” the authors wrote. “Observational studies have described a high prevalence of depression and anxiety in RA; [MDDs] are detected in 17% of RA patients, and local and systemic inflammation plays an important role in anxiety and depression.”

The authors reviewed previously conducted studies on the impact of depression on disease activity in RA and vice versa.

Patient-reported outcomes like baseline bodily pain and fatigue not only affect QoL and high disease activity but also likely increase depression. There is a relationship between the disease activity score using 28 joints and QoL, and patients with a higher degree of pain had a higher reduction in QoL, the researchers wrote.

A survey by the National Rheumatoid Arthritis Society found that 90% of patients with RA reported fatigue was the main factor causing low mood and depression, with 89% reporting they experienced chronic fatigue and 79% never being assessed to determine their level of fatigue.

“RA patients report the effect of the disease on their mental well-being and frequently describe tearfulness, irritability, frustration, anxiety, and depression,” the authors explained.

Depression is the most common mental health disorder associated with RA, and presents with low mood, low self-esteem, fatigue, lethargy, and more. In addition, MDD can present with more aggressive symptoms of depression and can potentially be fatal if left untreated since it also presents with suicidal ideation.

Studies have shown that depression reduces medication adherence and that patients with depression may have reduced physical exercise and social interaction because their coping responses to pain, fatigue, and disability are impaired.

“RA patients diagnosed with depression have reduced rates of clinically significant RA remission, increased pain, worse function and quality of life, and increased mortality,” the authors wrote. “PROs hence become an essential factor for optimising the holistic care of RA.”

The researchers noted that studies have found that biologic disease-modifying antirheumatic drugs (DMARDs) and conventional synthetic DMARDs can improve depressive symptoms in patients with RA. However, when depression is present in patients with RA before they start on biologic DMARDs, it can reduce treatment response.

“Further observational studies for early detection of anxiety and depression in RA patients using web-based questionnaires would be of help for both patients and clinicians,” the authors concluded.


Lwin MN, Serhal L, Holroyd C, Edwards CJ. Rheumatoid arthritis: the impact of mental health on disease: a narrative review. Rheumatol Ther. 2020;7(3):457-471. doi:10.1007/s40744-020-00217-4

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