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  1. J. K. Pedersen1,2,
  2. N. Risbo3,
  3. A. Pedersen3,
  4. L. Wang3,
  5. C. Havregaard Sørensen4,
  6. K. Andersen4,
  7. T. Ellingsen5
  1. 1Odense University Hospital, Svendborg Hospital, Department of Medicine, Svendborg, Denmark
  2. 2University of Southern Denmark, Department of Clinical Research, Odense, Denmark
  3. 3Aarhus University Hospital, Department of Clinical Epidemiology, Aarhus, Denmark
  4. 4Mental Health Services in the Region of Southern Denmark, Department of Psychiatry Odense, Odense, Denmark
  5. 5Odense University Hospital, Department of Rheumatology, Odense, Denmark


Background The occurrence of depression is increased in patients with rheumatoid arthritis (RA) compared with the background population. (1) Recently, we described that in RA the most frequent indication for filling antidepressant prescriptions is depression and the frequency of filling coincides with the occurrence of depression reported in the scientific literature. (2) In patients with stroke, depression defined as filling of antidepressants or a diagnosis with depression is associated with increased mortality risk and the risk is similar for both definitions of depression. (3)

Objectives We used the first filling of antidepressants as proxy for depression with the objective to describe the mortality risk associated with depression in patients with incident RA.

Methods We included patients diagnosed with incident RA (index date) from the nationwide DANBIO register (4) from January 1, 2008 to September 30, 2018. Participants were identified by unique personal registration numbers. Included patients were without a recorded filling of methotrexate (Anatomic Therapeutic Chemical code L01BA01) and antidepressants (N06A) in the Danish National Prescription Register or recorded hospital contacts with RA and depression (International Classification of Diseases (version 10) codes M05, M06, F32) in the Danish National Patient Register, three years prior to the index date. From the index date, we defined depression as first filling of antidepressants and collected death dates from the Danish Civil Registration System. The participants were followed until December 31, 2018 and all-cause mortality estimated in two dynamic risk periods: the period from the index date until first filling of antidepressants (if it occurred) and the period after filling of antidepressants. We calculated hazard rate ratios (HRR) by modelling filling of antidepressants as time-varying exposure for total follow-up and adjusted for potential confounders defined a priori: age, sex, comorbidity, cohabitation, employment status, highest attained education, and income. Cumulative mortality was described by Kaplan-Meier curves. Results were reported with 95% confidence intervals (CI).

Results Among 11,071 RA patients followed for 56,993 person-years, 1,095 (10%) filled prescriptions for antidepressants. The median age at diagnosis was 61 years, 66% were female, and 64% diagnosed with seropositive RA. Adjusted HRR was highest in the age group <55 years but also increased between 55-70 years, >70 years, among females and males, and in patients diagnosed with seropositive and seronegative RA (Table 1). The cumulative mortality is seen in Figure 1.

Table 1.

Conclusion Depression, defined as first filling of antidepressants, was associated with more than six-fold increased mortality risk in patients with incident RA.

References [1]Matcham F, et al. The prevalence of depression in rheumatoid arthritis: A systematic review and meta-analysis. Rheumatology 2013;52:2136-48.

[2]Pedersen JK, et al. No difference in antidepressant prescription in rheumatoid arthritis and controls. Results from a population-based, matched inception cohort. Scand J Rheumatol. 2021; Jun 29:1-7.

[3]Jørgensen TSH, et al. Incidence of depression after stroke, and associated risk factors and mortality outcomes, in a large cohort of Danish patients. JAMA Psychiatry 2016;73:1032-1040.

[4]Ibfelt EH, et al. The Danish nationwide clinical register for patients with rheumatoid arthritis: DANBIO. Clin Epidemiol 2016;8:737-42.

Acknowledgements The study was supported by the Danish Rheumatism Association.

Disclosure of Interests None declared.

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