Is there a higher risk of depression among specific populations of patients with rheumatoid arthritis?

By Tarun Sai LomteReviewed by Danielle Ellis, B.Sc.Mar 8 2024

In a recent study published in JAMA Network Open, researchers assessed the risk of depression following the diagnosis of rheumatoid arthritis (RA).

RA, a prevalent autoimmune disease, is characterized by systemic inflammation. The chronic nature of the disease necessitates lifelong treatment, often leading to comorbidities, including depression. Depression is highly prevalent among RA patients compared to the general population and has been associated with increased disease activity, pain exacerbation, elevated risk of myocardial infarction, less frequent remission, poor health-related quality of life, and higher health care utilization. Therefore, depression management and prevention are essential to improving the health and quality of life of RA patients.

About the study

In the present study, researchers examined associations of RA with subsequent depression risk in South Korea. They included subjects diagnosed with RA during 2010-17. Seropositive RA (SPRA) was defined using the International Classification of Diseases, Tenth Revision (ICD-10) codes and enrolment in the Rare and Intractable Diseases (RID) program.

RID program enrollment for SPRA required a positive test result for anticyclic citrullinated peptide antibodies or rheumatoid factors and a physician report indicating the fulfillment of RA classification criteria. Seronegative RA (SNRA) was defined using ICD-10 codes and prescription of disease-modifying anti-rheumatic drugs (DMARDs) for ≥ 270 days.

The team excluded subjects if they were aged under 20, had prior depression, missing data, or developed depression within a year post-index date. RA patients were matched to individuals without RA (controls) by sex, age, and index date. The study endpoint was a new diagnosis of depression. Participants were followed up from one year post-RA diagnosis until the diagnosis of depression, death, or December 31, 2019.

The Kaplan-Meier method was used to estimate the cumulative incidence of depression. Differences between groups were evaluated using log-rank tests. Cox regression analyses estimated adjusted hazard ratios and 95% confidence intervals for the risk of depression. The association between depression risk and the type of DMARDs used was also evaluated.

Analyses were adjusted for sex, age, smoking/alcohol status, income, body mass index, physical activity, diabetes, chronic kidney disease, hyperlipidemia, and hypertension. Besides, stratified analyses were conducted by sex, age, comorbidities, and health behaviors. Restricted mean survival time (RMST) differences were analyzed between groups by sex and age.

Findings

Overall, 230,922 participants aged 54.6, on average, were included for analysis. There were 38,487 RA patients and 192,435 controls; most participants were female (71%). Among RA patients, 11,645 were seronegative, and 26,842 were seropositive. RA patients were more likely to be non-drinkers and less likely to be obese. SPRA patients were more likely to be female, older, non-drinkers, and less likely to be obese than SNRA patients.

The median follow-up duration was 4.1 years, during which 6,422 RA patients and 20,641 had newly developed depression. RA patients had a higher risk of depression than controls. Moreover, SPRA and SNRA groups had elevated depression risk compared to controls. Among RA patients with depression, 402 were prescribed biological or targeted synthetic DMARDs, and 6,020 were prescribed only conventional synthetic DMARDs.

Notably, the incidence of depression among RA patients was consistently lower among recipients of targeted synthetic or biological DMARDs than non-recipients. Stratified analyses yielded findings consistent with the primary analysis. RMST differences were variable across age groups, with a higher difference in the ≥ 60-year age group.

Conclusions

In sum, the researchers observed a 1.66-fold increased depression risk among RA patients relative to those without RA. There was no significant difference in depression risk by the serologic status of RA, with both SNRA and SPRA groups exhibiting an increased risk. RA patients receiving targeted synthetic or biological DMARDs had lower risks than those who did not. Nevertheless, the study has a few limitations. Notably, disease activity was inaccessible, resulting in limited evaluation of RA severity.

Moreover, information on depression levels at the index date was not available. Besides, because participation was limited to those undergoing health screening, participants might have been healthier or engaged more in healthy behaviors than the general population.

Taken together, the findings suggest an increased depression risk among RA patients, irrespective of RA serologic status, age, sex, and behavioral factors, warranting consistent screening of RA patients and comprehensive healthcare to address their physical and mental well-being.