An Overview of Psychiatric Comorbidities in Rheumatoid Arthritis

elderly woman with pain
A deeper insight into the burden of psychiatric comorbidities in patients with rheumatoid arthritis.

The incidence and prevalence of rheumatoid arthritis (RA), the most common autoimmune inflammatory arthritis, is increasing worldwide; in 2014, RA affected an estimated 1.28 to 1.36 million adults.1 A growing body of research has indicated that compared with patients without RA, those with RA are disproportionately affected by psychiatric disorders, particularly anxiety and depression.2,3 Psychiatric disorders in patients with RA not only affect functioning and quality of life, but they have been associated with poorer RA outcomes, including a greater frequency of flares, lower odds of achieving remission, and increased mortality.4

Psychiatric Comorbidities and Healthcare Utilization

Psychiatric comorbidities in RA lead to higher rates of healthcare utilization. In a retrospective cohort study by Carol Hitchon, MD MSc, clinician scientist at the University of Manitoba in Winnipeg, Canada, and colleagues,5 an analysis of health records of 12,984 patients with RA and 64,510 matched control participants for the period between 2006 and 2016 showed that patients with RA with vs without comorbid psychiatric disorders (depression, anxiety, bipolar disorder, or schizophrenia) received more types of medications, had more ambulatory physician visits and hospitalizations, and greater length of hospital stays. Investigators concluded that managing psychiatric comorbidities effectively may reduce utilization among patients with RA.

Treatment Decisions

We spoke with Dr Hitchon who suggested that the presence of psychiatric disorders can complicate treatment decisions and subsequent outcomes. “We know that psychiatric comorbidity [affects] how people experience pain and this may or may not be associated with joint inflammation,” she added. “This type of pain may be treated differently than if the pain is due to joint inflammation.” Psychiatric disorders can also complicate the assessment of RA activity, since low mood or depression can influence the patient-reported components of standardized instruments such as disease activity score in 28 joints.6 

Prevalence of Depression

Depression, the most common psychiatric comorbidity of RA, has been estimated to occur in 9.5% to 41.5% of patients with RA.2,7 A recent meta-analysis concluded that 16.8% of patients with RA had comorbid major depressive disorder (MDD), based on pooled estimates from studies that identified depression with psychiatric interviews, the gold standard for diagnosis.7 The reasons for the prevalence of depression in patients with RA typically include the adverse effects that chronic pain, fatigue, and functional limitations have on social roles and quality of life.4

We also spoke with Mellissa Withers, PhD, MHS of the USC Institute on Inequalities in Global Health at the University of Southern California Keck School of Medicine, who noted that the pain and limitations associated with RA can negatively affect many aspects of patients’ lives. “They may not be able to participate in the things that used to bring them joy, like hobbies, social interactions, or a job. Patients are especially at risk for depression and anxiety when they are first diagnosed with RA. You can imagine — they hear that they are facing a debilitating, degenerative, long-term illness. So it can be very upsetting. It brings a lot of fear of what their futures will be like.”

Pathophysiology of Depression in RA

Shared inflammatory pathways are also widely believed play a role in the frequent co-occurrence of depression and RA. Studies have shown that proinflammatory cytokines implicated in RA, such as tumor necrosis factor (TNF) α, interleukin (IL)-6 and IL-1β, are overexpressed in patients with depression compared with healthy control participants.4 In addition to causing chronic joint inflammation and damage to the cartilage and bone, excessive levels of these cytokines may contribute to depression by having detrimental effects on neuroendocrine function, neurotransmitter metabolism, and brain structures. Increased serum and/or plasma concentrations of C-reactive protein, often seen in RA populations, are also present in patients with depression or anxiety.6 

The Role of Rheumatologists

An analysis of audio recordings taken at patient visits for RA showed that rheumatologists rarely brought up the topic of depression, even among patients whose depressive symptoms were moderate to severe.8 Dr Withers recommended that rheumatologists incorporate depression identification and management into patient care plans, especially since patients may not know that a rheumatology visit is an appropriate time to bring up mental health issues. “It is critical to screen patients regularly for depression and other disorders and to follow those with scores that suggest mild depression to determine if the depression worsens over time,” she said. “If the patient scores indicate depression or a psychiatric disorder, the rheumatologist can then refer them for consultation with a mental health professional.”

Lekeisha Sumner, PhD, ABPP, a licensed clinical psychologist with a board certification in clinical health psychology and author of several papers on the psychosocial aspects of rheumatologic diseases, stated that depression and anxiety are “grossly underdiagnosed and treated” in rheumatologic diseases despite their high prevalence. “The provider-patient relationship is key in health outcomes and especially important when discussing sensitive topics that have historically been stigmatized,” she advised. “Leveraging rapport with your patient to ask about how their emotional strain presents at each visit invites them to give voice to the often-silent suffering that they commonly experience. Keep in mind that some of your patients will likely have alexithymia, which not only complicates their recovery but makes it more difficult for them to identify and process their emotions.” Dr Sumner recommended that rheumatologists use simple screening tools such as the Generalized Anxiety Disorder and Patient Health Questionnaire to assess mental health.

“Conceptualizing symptoms of anxiety and depression as par for the course in RA conditions is ill-advised as they contribute to increased burden on the patient, diminishes overall functioning, increased pain sensitivity, affects long-term disease activity, remission, response to treatment, and quality of life,” Dr Sumner noted. “Recognize that your patient has likely experienced difficulties with sexual functioning, ability to earn a living and engage in daily activities with ease, resulting in shifts in identity and confidence to effectively self-manage their condition. Targeting immunologic alterations will help alleviate psychiatric distress, along with using a multidisciplinary approach to care that includes mental health professions are all key to disease management and promoting adaptive adjustment and coping.”


  1. Hunter TM, Boytsov NN, Zhang X, Schroeder K, Michaud K, Araujo AB. Prevalence of rheumatoid arthritis in the United States adult population in healthcare claims databases, 2004–2014. Rheumatol Int. 2017;37(9):1551-1557.
  2. Nerurkar L, Siebert S, McInnes IB, Cavanagh J. Rheumatoid arthritis and depression: an inflammatory perspective. Lancet Psychiatry. 2019;6(2):164-173.
  3. Anyfanti P, Gavriilaki E, Pyrpasopoulou A, et al. Depression, anxiety, and quality of life in a large cohort of patients with rheumatic diseases: common, yet undertreated. Clin Rheumatol. 2016;35(3):733-739.
  4. Vallerand IA, Patten SB, Barnabe C. Depression and the risk of rheumatoid arthritis. Curr Opin Rheumatol. 2019;31(3):279-284.
  5. Hitchon CA, Walld R, Peschken CA, et al. The impact of psychiatric comorbidity on health care use in rheumatoid arthritis: a population-based study. Arthritis Care Res. Published online July 23, 2020. doi:10.1002/acr.24386
  6. 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.
  7. Matcham F, Rayner L, Steer S, Hotopf M. The prevalence of depression in rheumatoid arthritis: a systematic review and meta-analysis. Rheumatol Oxf Engl. 2013;52(12):2136-2148.
  8. Sleath B, Chewning B, de Vellis BM, et al. Communication about depression during rheumatoid arthritis patient visits. Arthritis Rheum. 2008;59(2):186-191.