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Comorbid depression, RA amplifies pain, inflammation, fatigue
Rheumatoid arthritis, an autoimmune disease that affects approximately 1.3 million adults in the United States, can cause pain, disability and long-term joint damage. Depression, another debilitating and disruptive condition, was identified in 8.1% of Americans aged 20 years and older during a 2-week period between 2013 and 2016.
“It’s been proposed that it is potentially bidirectional,” Kirsten Fiest, PhD, epidemiologist and assistant professor at the University of Calgary School of Medicine, told Healio. “That means that some depressive symptoms can worsen RA and RA can worsen depression. There is a sort of synergism between the two conditions in terms of pain and overall functioning, inability to work and reduced quality of life.”
Cytokines, RA medications affect depression
Despite the bidirectional association between RA and depression, the causality and the sequence of disease manifestation is not clear. Although pain and disability are associated with depression in patients with RA, inflammation may also serve as a link between the two conditions. Certain cytokines, such as interleukin-1, interleukin-6 and tumor necrosis factor-alpha, play a role in the pain and inflammation of RA.
“Depression is known to increase production of some inflammatory markers,” Fiest said. “These inflammatory cytokines could lead to higher RA disease activity.”
According to a study from the National Health and Nutrition Examination Survey that included data on 10,036 patients with RA, levels of C-reactive protein were 31% higher in individuals with symptoms of depression than in those with no symptoms. The level of inflammation seen in a patient who is depressed would likely be proportional to the severity and chronicity of the depression, according to Fiest.
“One depressive episode in a reaction to a life event might cause some short-term elevations in these inflammatory markers,” she said. “However, in an individual with chronic, long-lasting depression, there certainly is a lot of evidence to suggest that multiple pathways in the brain and other stress-related organs and responses that are affected by depression.”
In a person who is genetically susceptible to RA, the inflammation caused by depression could potentially lead to the development of the joint disease.
Patients with RA who are also depressed are more likely to have negative perceptions of their condition and its symptoms compared with patients who have RA but not depression. The pain, inflammation and fatigue associated with RA can also exacerbate depressive symptoms.
Some research has suggested that depression decreases the likelihood of remission in patients with RA. The prospective, multicenter NOR-DMARD study included 1,450 patients (mean age, 54.4 years) who recently started first-time treatment with TNF inhibitors or methotrexate. At baseline, 40.7% of patients with RA reported moderate depression/anxiety and 2.8% reported extreme depression/anxiety. At 3 and 6 months, these baseline levels of depression/anxiety were negatively associated with DAS28 <2.6, SDAI 3.3 and ACR/EULAR Boolean remission.
Certain RA medications in combination with SSRIs may prevent remission of depression in patients with comorbid RA and depression, according to Feist.
Depression symptoms, treatment affect RA activity
The management of comorbid RA and depression requires clinicians to carefully weigh the benefits and risks of therapies for both conditions.
SSRIs may also interact with non-steroidal anti-inflammatory drugs, such as aspirin, which are commonly used to treat RA. Fiest said these drugs, when taken together, can increase the risk for gastrointestinal bleeding.
A meta-analysis led by Fiest included six trials that evaluated the use of pharmacologic treatments for depression in patients with RA, as well as one trial that examined psychological interventions and one that looked at both approaches. The standardized mean differences of depression or anxiety scores at post-assessment were pooled between treatment and comparison groups and grouped according to whether the agent was active (such as an antidepressant) or inactive (such as placebo).
Active comparators were more likely to decrease depressive symptoms (standardized mean difference, –0.79; 95% CI, –1.34 to –0.25). No reduction in symptoms was observed in trials of an inactive comparator (SMD, –0.21; 95% CI, –1.28 to 0.85).
The one trial to study a psychological intervention alone demonstrated no benefit for the treatment of depression, but this finding was not statistically significant. However, certain psychological and behavioral approaches have shown value in the treatment of depression and RA, according to Fiest.
“The literature is young,” she said. “It’s increasing in volume, but there’s still a lot we don’t know.”
References
- American College of Rheumatology. Prevalence Statistics. Available at: https://www.rheumatology.org/Learning-Center/Statistics/Prevalence-Statistics. Accessed on Oct. 16, 2018.
- CDC. Prevalence of Depression Among Adults Aged 20 and Over: United States, 2013-2016. Available at: https://www.cdc.gov/nchs/products/databriefs/db303.htm. Accessed on Oct. 16, 2018.
- Arthritis Foundation. The Arthritis-Depression Connection. Available at: https://www.arthritis.org/living-with-arthritis/comorbidities/depression-and-arthritis/depression-rheumatoid-arthritis.php. Accessed on Oct 16, 2018.
- Michelsen B. et al. Arthritis Rheumatology. 2016; https://acrabstracts.org/abstract/do-depression-and-anxiety-reduce-the-chance-of-remission-in-rheumatoid-arthritis-and-psoriatic-arthritis/
- Fiest KM et al. J Clin Rheumatology. 2018;doi:10.1097/RHU.0000000000000489.
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