Abstract
OBJECTIVE:
Rheumatoid arthritis (RA) is a costly and crippling autoimmune disease that can lead to the development of depression, contributing to suboptimal clinical outcomes. However, no longitudinal studies have identified an association between rheumatoid arthritis and subsequent depression. This study aimed to investigate the incidence and risk factors of depression among RA patients in Taiwan.
METHODS:
Using Taiwan's National Health Insurance Research Database, we identified 3,698 newly diagnosed RA patients aged 18 years or older, together with 7,396 subjects without RA matched by sex, age and index date, between 2000 and 2004. The incidence of depression and the risk factors among RA cases were evaluated using Cox proportional-hazard regression.
RESULTS:
The incidence of depression was 1.74-fold greater in the RA cohort than in the non-RA cohort (11.80 versus 6.89 per 1,000 person-years; p<0.01). Multivariate analysis showed that RA subjects who were female, were older, or had comorbidities such as stroke, chronic kidney disease, or cancer had a significantly greater risk of depression compared with those without these conditions.
CONCLUSION:
This population-based cohort study showed a strong relationship between RA and a subsequent risk of depression. The findings could be beneficial to healthcare providers for identifying individuals with a higher predisposition for depression, thereby possibly facilitating the provision of an appropriate rehabilitation intervention after RA onset to support the patient's adaptation.
Rheumatoid Arthritis; Depression; Risk Factor; Cohort Study
INTRODUCTION
Rheumatoid arthritis (RA) is a debilitating disease characterized by chronic
symmetric polyarthritis involving peripheral small joints that affects 0.3-1.0% of
the population worldwide (11 Woolf AD, Pfleger B. Burden of major musculoskeletal conditions.
Bull World Health Organ. 2003;81(9):646-56.). Most
individuals first experience RA between 30 and 50 years of age (22 Rindfleisch JA, Muller D. Diagnosis and management of rheumatoid
arthritis. Am Fam Physician. 2005;72(6):1037-47.). Approximately 20-30% of these individuals
are unable to work within 3 years following diagnosis, which places a tremendous
burden on the patients, their families and the healthcare system (33 Sokka T. Work disability in early rheumatoid arthritis. Clin Exp
Rheumatol. 2003;21:S71-4.). Accordingly, a report from the American
College of Rheumatology Subcommittee showed that RA is responsible for 250,000
hospitalizations and 9 million physician visits each year (44 American College of Rheumatology Subcommittee on Rheumatoid
Arthritis. Guidelines for the management of rheumatoid arthritis: 2002 update.
Arthritis Rheum. 2002;46(2):328-46.). Additionally, Birnbaum et al. (55 Birnbaum H, Pike C, Kaufman R, Maynchenko M, Kidolezi Y, Cifaldi
M. Societal cost of rheumatoid arthritis patients in the US. Curr Med Res Opin.
2010;26(1):77-90, http://dx.doi.org/10.1185/03007990903422307.
http://dx.doi.org/10.1185/03007990903422...
) reported that the annual direct medical costs for RA in the
US were $19.3 billion, with the total societal costs (the sum of direct costs
and indirect costs) estimated to exceed $39 billion.
RA not only results in enormous economic losses but also presents a significant
public health problem. Recently, RA has been proven to be a major risk factor for
many chronic conditions such as cancer, cardiovascular disease, kidney dysfunction
and respiratory disease (22 Rindfleisch JA, Muller D. Diagnosis and management of rheumatoid
arthritis. Am Fam Physician. 2005;72(6):1037-47.,66 Gabriel S, Michaud K. Epidemiological studies in incidence,
prevalence, mortality, and comorbidity of the rheumatic diseases. Arthritis Res
Ther. 2009;11(3):229, http://dx.doi.org/10.1186/ar2669.
http://dx.doi.org/10.1186/ar2669...
). A review by Sokka et al. reported that RA
patients had a 50-60% greater risk of death from all causes compared with
individuals without RA (77 Sokka T, Abelson B, Pincus T. Mortality in rheumatoid arthritis:
2008 update. Clinical Exp Rheumatol. 2008;26:S35-61.). Due to the
irreversible nature of RA and the poor clinical responses of RA patients,
psychiatric disorders, especially depression, are commonly found among RA patients.
Indeed, the prevalence of depression among RA patients is estimated to range from
14.8 to 38.8% (88 Matcham F, Rayner L, Steer S, Hotopf M. The prevalence of
depression in rheumatoid arthritis: a systematic review and meta-analysis.
Rheumatology. 2013;52(12):2136-48,
http://dx.doi.org/10.1093/rheumatology/ket169.
http://dx.doi.org/10.1093/rheumatology/k...
) and patients with RA are
five times more likely to experience depression than the general population (99 Isik A, Koca S, Ozturk A, Mermi O. Anxiety and depression in
patients with rheumatoid arthritis. Clin Rheumatol. 2007;26(6):872-8,
http://dx.doi.org/10.1007/s10067-006-0407-y.
http://dx.doi.org/10.1007/s10067-006-040...
). RA patients suffering from concomitant
depression had a 7.2% ($12,225 vs. $11,404) increase in
medical costs (1010 Joyce AT, Smith P, Khandker R, Melin JM, Singh A. Hidden cost of
rheumatoid arthritis (RA): estimating cost of comorbid cardiovascular disease
and depression among patients with RA. J Rheumatol. 2009;36(4):743-52,
http://dx.doi.org/10.3899/jrheum.080670.
http://dx.doi.org/10.3899/jrheum.080670...
) and their likelihood of
mortality compared with patients with RA only was more than doubled (1111 Ang DC, Choi H, Kroenke K, Wolfe F. Comorbid depression is an
independent risk factor for mortality in patients with rheumatoid arthritis.
J Rheumatol. 2005;32(6):1013-9.). Therefore, it is important to clarify the
factors that may lead to depression and to then incorporate appropriate treatment
for these factors into the routine care of RA patients.
Although some studies on depression among RA subjects have been conducted, most have
been performed in Western countries (99 Isik A, Koca S, Ozturk A, Mermi O. Anxiety and depression in
patients with rheumatoid arthritis. Clin Rheumatol. 2007;26(6):872-8,
http://dx.doi.org/10.1007/s10067-006-0407-y.
http://dx.doi.org/10.1007/s10067-006-040...
,1212 Murphy LB, Sacks JJ, Brady TJ, Hootman JM, Chapman DP. Anxiety
and depression among US adults with arthritis: prevalence and correlates.
Arthritis Care Res. 2012;64(7):968-76.
13 Margaretten M, Barton J, Julian L, Katz P, Trupin L, Tonner C,
et al. Socioeconomic determinants of disability and depression in patients with
rheumatoid arthritis. Arthritis Care Res. 2011;63(2):240-6,
http://dx.doi.org/10.1002/acr.20345.
http://dx.doi.org/10.1002/acr.20345...
-1414 Rivero-Carrera NN, Serra-Bonett N, Snih SA, Duque-Criollo JV,
Rodríguez MA. Risk factors associated with depressive symptoms in
Venezuelan patients with rheumatoid arthritis. J Clin Rheumatol.
2011;17(4):218-9,
http://dx.doi.org/10.1097/RHU.0b013e31821c7af3.
http://dx.doi.org/10.1097/RHU.0b013e3182...
).
In particular, Chinese patients often consider depression to be a taboo subject and
are highly reluctant to openly discuss this problem with others (1515 Yeh YH, Lin CH. A questionnaire study of depression related
help-seeking behavior among the general public in Taiwan.
Formosa J Men Health. 2005;19(2):125-48.). Previous studies of Chinese RA patients
have often focused on disease outcomes during pregnancy (1616 Lin HC, Chen SF, Lin HC, Chen YH. Increased risk of adverse
pregnancy outcomes in women with rheumatoid arthritis: a nationwide
population-based study. Ann Rheum Dis. 2010;69(4):715-7,
http://dx.doi.org/10.1136/ard.2008.105262.
http://dx.doi.org/10.1136/ard.2008.10526...
), epidemiological reports (1717 Yu KH, See LC, Kuo CF, Chou IJ, Chou MJ. Prevalence and
incidence in patients with autoimmune rheumatic diseases: a nation-wide
population-based study in Taiwan. Arthritis Care Res. 2013;65(2):244-50,
http://dx.doi.org/10.1002/acr.21820.
http://dx.doi.org/10.1002/acr.21820...
), or the subsequent risk of cancer following RA onset (1818 Chen YJ, Chang YT, Wang CB, Wu CY. The risk of cancer in
patients with rheumatoid arthritis: a nationwide cohort study in Taiwan.
Arthritis Rheum. 2011;63(2):352-8,
http://dx.doi.org/10.1002/art.30134.
http://dx.doi.org/10.1002/art.30134...
). Consequently, only limited data are
available on psychological issues, especially depression, among Asian patients with
RA. Of the few studies conducted that have examined factors related to depression
among Chinese RA patients, there are major weaknesses such as the absence of a
control group, a small sample size, or a cross-sectional design (1919 Lok EY, Mok CC, Cheng CW, Cheung EF. Prevalence and determinants
of psychiatric disorders in patients with rheumatoid arthritis. Psychosomatics
2010;51(4):338, http://dx.doi.org/10.1176/appi.psy.51.4.338.
http://dx.doi.org/10.1176/appi.psy.51.4....
,2020 Sato E, Nishimura K, Nakajima A, Okamoto H, Shinozaki M, Inoue
E, et al. Major depressive disorder in patients with rheumatoid arthritis. Mod
Rheumatol. 2013;23(2):237-44,
http://dx.doi.org/10.3109/s10165-012-0643-8.
http://dx.doi.org/10.3109/s10165-012-064...
).
To fill this gap in the literature, we conducted a follow-up study to assess the
association between RA and the subsequent risk of depression, together with risk
factors, in Asian patients using claims data obtained from the National Health
Insurance (NHI) of Taiwan. Although this is a preliminary study of depression in RA
patients, its findings should assist healthcare providers in identifying potential
cases of depression and provide an empirical rationale for initiating more timely
and efficient interventions for RA patients.
METHODS
Data sources
All analytic data were retrieved from the Longitudinal Health Insurance Database
(LHID), which is maintained by the Bureau of National Health Insurance (BNHI)
and provided to scientists in Taiwan for research purposes. In 1995, Taiwan
launched a single-payer NHI Program to remove the financial barriers to medical
care for all legal residents. At the end of 2010, >99% of Taiwan's
population had enrolled in this program (2121 National Health Insurance Database: LHID 2000.
http://nhird.nhri.org.tw/date_cohort.htm#2.
http://nhird.nhri.org.tw/date_cohort.htm...
). The LHID is a subset of the NHI database and contains
comprehensive utilization and enrollment information for one million randomly
selected NHI beneficiaries, representing 5% of all enrollees in Taiwan in 2000.
Because a multistage, stratified, systematic sampling method was used for this
study, there were no statistically significant differences regarding sex or age
between the sample group and the total number of enrollees (2121 National Health Insurance Database: LHID 2000.
http://nhird.nhri.org.tw/date_cohort.htm#2.
http://nhird.nhri.org.tw/date_cohort.htm...
). This study was approved by the local
institutional review board and ethics committee of Buddhist Dalin Tzu Chi
Hospital, Taiwan (No. B101030014).
Study subjects
Diagnoses in the patient insurance claims data were coded according to the
International Classification of Disease, 9th Revision, Clinical
Modification (ICD-9-CM). The LHID records were used to identify adult patients
with RA aged ≥18 years and newly diagnosed between 2000 and 2004.
Patients who were identified with an ICD code of 714.0 comprised the RA cohort.
To eliminate errors resulting from misclassification, we selected RA subjects
who had at least 2 RA diagnoses in the ambulatory service or those who were
admitted to the hospital with a primary RA diagnosis during the 5-year period.
This approach was based on the method adopted by former researchers using
administrative databases (2222 Scherrer JF, Virgo KS, Zeringue A, Bucholz KK, Jacob T, Johnson
RG, et al. Depression increases risk of incident myocardial infarction among
Veterans Administration patients with rheumatoid arthritis. Gen Hosp Psychiatry.
2009;31(4):353-9,
http://dx.doi.org/10.1016/j.genhosppsych.2009.04.001.
http://dx.doi.org/10.1016/j.genhosppsych...
,2323 Tsai TY, Livneh H, Lu MC, Tsai PY, Chen PC, Sung FC. Increased
risk and related factors of depression among patients with COPD: a
population-based cohort study. BMC Public Health. 2013;13(1):976,
http://dx.doi.org/10.1186/1471-2458-13-976.
http://dx.doi.org/10.1186/1471-2458-13-9...
). The index date was defined as the date
of the first RA diagnosis.
Based on gender, age and index date, each RA patient was matched with 2 control-group patients from a reference population not registered with an RA diagnosis. Each subject in the control group was assigned the same index date as the corresponding RA patient. After excluding subjects with a history of depression at baseline, a total of 3,698 RA patients and 7,396 non-RA control subjects were included in the data analysis. Patients were considered to have a history of depression if they had ≥2 outpatient visits or at least one inpatient claim of depression (ICD-9-CM codes of 296.2, 296.3, 300.4 or 311) since 1996, when the computerized claims data from the LHID were available, until the date of cohort entry. All subjects were followed up to the end of 2011 to measure the incidence of depression based on the above-mentioned criteria: at least two ambulatory visits or one hospitalization with the diagnosis of depression. The date of their first medical visit due to depression was established as the starting point for their time at risk with depression. Follow-up person-years (PYs) were calculated as the time interval from the entry date to the earliest occurrence of one of the following: a diagnosis of depression, the date of withdrawal from insurance, or December 31, 2011.
Demographic variables and disease characteristics
The demographic variables used in this study included age, gender, income for estimating insurance payment and urbanization level of the subject's residential area. The monthly incomes were divided into 3 levels: ≤New Taiwan Dollar (NTD) 17,880, NTD 17,881-NTD 43,900, and ≥NTD 43,901. Urbanization levels were divided into 3 strata based on population density: urban (levels 1-2), suburban (levels 3-4) and rural (levels 5-7) areas. Level 1 refers to the “most urbanized” and level 7 refers to the “least urbanized” communities (2424 Liu CY, Hung YT, Chuang YL, Chen YJ, Weng WS, Liu JS, et al. Incorporating development stratification of Taiwan townships into sampling design of large scale health interview survey. J Health Manag. 2006;4(1):1-22.). Disease characteristics included the presence of a chronic disease such as hypertension (ICD-9-CM 401-405), stroke (ICD-9-CM 430-438), diabetes (ICD-9-CM 250), heart disease (ICD-9-CM 410-429), chronic kidney disease (ICD-9-CM 585) and cancer (ICD-9-CM 140-208). Additionally, medication usage was stratified into two groups according to whether the subjects had received DMARDs or biological agents for more than three months after the index date.
Statistical analysis
The χ2 test was used to examine differences in demographic variables and disease characteristics between the RA and control cohorts. The depression incidence rate for the 2 cohorts was presented as the number of cases per 1,000 PYs. A Cox proportional hazards regression analysis was applied to compute the hazard ratio (HR) and 95% confidence interval (CI) of depression for RA compared with the control cohort. The multivariate Cox proportional hazards model was used to identify risk factors that might predict depression and their adjusted hazard ratio (aHR) within the RA cohort. All analyses were performed using SAS version 9.3 (SAS Institute Inc., Cary, NC, USA) and p<0.05 was considered statistically significant.
RESULTS
Baseline characteristics and depression incidence between the two cohorts
The distributions of demographic variables and disease characteristics for the RA and control cohorts are shown in Table 1. RA patients were more likely to reside in a rural area (p<0.01), take medications (p<0.01) and be diagnosed with comorbidities such as stroke and diabetes (p<0.05 for both comorbidities).
Among the study sample of 11,094 patients, a total of 905 first episodes of depression occurred - 413 among the RA patients and 492 among the control subjects - during the follow-up of 34,992.62 and 71,449.94 PYs, respectively. The incidence of depression in the RA cohort was greater than that in the control group (11.80 vs. 6.89 per 1,000 PYs), with an aHR of 1.74 (95% CI 1.48, 1.95; Table 2).
Risk factors of depression in RA subjects
A multivariate Cox proportional-hazard regression analysis was used to estimate the aHR of depression among RA patients based on demographic data and disease characteristics (Table 3). The data showed that age and gender are significantly related to the risk of depression in RA patients. In addition, the risk of depression was 19% greater for subjects aged ≥70 years compared with those aged <18 years (95% CI 1.02-1.38). Compared with male gender, female gender was related to an aHR of 1.77 for depression (95% CI 1.52-2.07). Additionally, the presence of a comorbidity increased the risk of depression, with patients with cancer having the highest risk (aHR: 2.47, 95% CI 1.46-4.20), followed by those with chronic kidney disease (aHR: 2.32, 95% CI 1.10-4.88) and stroke (aHR: 1.84, 95% CI 1.14-2.96).
DISCUSSION
This is the first study to utilize a national administrative database to address the relationship between RA and subsequent depression in an Asian population. Due to the relatively low RA incidence, a large sample size is required to obtain sufficient statistical power for a proper analysis. Previous studies have nearly always been conducted using hospitalized patients, which may limit the number of patients observed and lead to possible selection bias. Therefore, the present population-based data using age- and sex-matched control groups allowed for a better validation of the results than the data obtained in previous studies. Additionally, our cohort study design using nationwide claims-based data allowed us to examine the temporal association between RA and depression risk.
Our study suggests that RA patients have a 74% increased risk of depression compared
with similarly aged control subjects in a general population, which is in agreement
with the results of prior studies conducted in Western populations (99 Isik A, Koca S, Ozturk A, Mermi O. Anxiety and depression in
patients with rheumatoid arthritis. Clin Rheumatol. 2007;26(6):872-8,
http://dx.doi.org/10.1007/s10067-006-0407-y.
http://dx.doi.org/10.1007/s10067-006-040...
,1212 Murphy LB, Sacks JJ, Brady TJ, Hootman JM, Chapman DP. Anxiety
and depression among US adults with arthritis: prevalence and correlates.
Arthritis Care Res. 2012;64(7):968-76.,1313 Margaretten M, Barton J, Julian L, Katz P, Trupin L, Tonner C,
et al. Socioeconomic determinants of disability and depression in patients with
rheumatoid arthritis. Arthritis Care Res. 2011;63(2):240-6,
http://dx.doi.org/10.1002/acr.20345.
http://dx.doi.org/10.1002/acr.20345...
,2525 Wolfe F, Michaud K. Predicting depression in rheumatoid
arthritis: the signal importance of pain extent and fatigue, and comorbidity.
Arthritis Rheum. 2009;61(5):667-73,
http://dx.doi.org/10.1002/art.24428.
http://dx.doi.org/10.1002/art.24428...
). Possible explanations for our results include the
following. First, RA is a chronic, unremitting disease with no known cure. Severe RA
can cause progressive functional impairments that affect community involvement,
work, family life and social and recreational activities. These effects may lower
the patient's self-esteem and self-efficacy thereby inducing a higher risk for
depression (2626 Geenen R, Newman S, Bossema ER, Vriezekolk JE, Boelen PA.
Psychological interventions for patients with rheumatic diseases and anxiety or
depression. Best Prac Res Clin Rheumatol. 2012;26(3):305-19,
http://dx.doi.org/10.1016/j.berh.2012.05.004.
http://dx.doi.org/10.1016/j.berh.2012.05...
). Second, the debilitating and
continuous physical RA symptoms may trigger “learned helplessness”
cognitions, such that one's inability to successfully cope with physical
deterioration and life-threatening situations results in increased levels of
uncertainty, unpredictability and ultimately, emotional distress and depression
(2727 Neville KL. Uncertainty in illness: an integrative review.
Orthop Nurs. 2003;22(3):206-14,
http://dx.doi.org/10.1097/00006416-200305000-00009.
http://dx.doi.org/10.1097/00006416-20030...
). Third, the symptoms manifested by
RA are directly associated with experiencing chronic pain and the latter has been
linked to increased levels of depression (2828 Walker JG, Jackson HJ, Littlejohn GO. Models of adjustment to
chronic illness: using the example of rheumatoid arthritis. Clin Psychol Rev.
2004;24(4):461-88, http://dx.doi.org/10.1016/j.cpr.2004.03.001.
http://dx.doi.org/10.1016/j.cpr.2004.03....
). Fourth, tumor necrosis factor-α (TNF-α) and interleukin 1
(IL-1) are the pivotal cytokines involved in RA (2929 Malemud CJ, Miller AH. Pro-inflammatory cytokine-induced
SAPK/MAPK and JAK/STAT in rheumatoid arthritis and the new anti-depression
drugs. Expert Opin Ther Targets. 2008;12(2):171-83,
http://dx.doi.org/10.1517/14728222.12.2.171.
http://dx.doi.org/10.1517/14728222.12.2....
) and these pro-inflammatory agents have been considered as pathogenic
factors associated with the mechanism of developing depression (2626 Geenen R, Newman S, Bossema ER, Vriezekolk JE, Boelen PA.
Psychological interventions for patients with rheumatic diseases and anxiety or
depression. Best Prac Res Clin Rheumatol. 2012;26(3):305-19,
http://dx.doi.org/10.1016/j.berh.2012.05.004.
http://dx.doi.org/10.1016/j.berh.2012.05...
,3030 Margaretten M, Julian L, Katz P, Yelin E. Depression in patients
with rheumatoid arthritis: description, causes and mechanisms.
Int J Clin Rheumatol. 2011;6(6):617-23.).
In fact, a meta-analysis of 22 studies indicated that inflammatory cytokines may
regulate adult neurogenesis to induce hippocampal neurogenesis atrophy, which has
been implicated as a key contributing factor in the pathophysiology of depression
and is a target of novel treatment strategies (3131 Hannestad J, DellaGioia N, Bloch M. The effect of antidepressant
medication treatment on serum levels of inflammatory cytokines: a meta-analysis.
Neuropsychopharmacology. 2011;36(12):2452-9,
http://dx.doi.org/10.1038/npp.2011.132.
http://dx.doi.org/10.1038/npp.2011.132...
).
The incidence of depression among RA patients in our study was lower than that in a
previous report (11.80/1,000 PYs vs. 55.0/1,000 PYs) (2525 Wolfe F, Michaud K. Predicting depression in rheumatoid
arthritis: the signal importance of pain extent and fatigue, and comorbidity.
Arthritis Rheum. 2009;61(5):667-73,
http://dx.doi.org/10.1002/art.24428.
http://dx.doi.org/10.1002/art.24428...
). This variation may be due to
methodological discrepancies such as variations in sample sizes and differences in
the assessment tools employed. In this previous report (2525 Wolfe F, Michaud K. Predicting depression in rheumatoid
arthritis: the signal importance of pain extent and fatigue, and comorbidity.
Arthritis Rheum. 2009;61(5):667-73,
http://dx.doi.org/10.1002/art.24428.
http://dx.doi.org/10.1002/art.24428...
), the psychiatric diagnosis of depression was made based on
a self-administered questionnaire that assessed symptoms only, which may have
reduced the accuracy of the data due to recall bias. In addition, due to their
conservative Asian culture, Chinese subjects tend to stigmatize psychiatric illness
and seldom discuss or openly seek regular psychiatric treatment for this issue
(1515 Yeh YH, Lin CH. A questionnaire study of depression related
help-seeking behavior among the general public in Taiwan.
Formosa J Men Health. 2005;19(2):125-48.). Notably, some studies have reported
that <20% of RA patients were treated and referred to appropriate psychiatric
services after the onset of the disease (1919 Lok EY, Mok CC, Cheng CW, Cheung EF. Prevalence and determinants
of psychiatric disorders in patients with rheumatoid arthritis. Psychosomatics
2010;51(4):338, http://dx.doi.org/10.1176/appi.psy.51.4.338.
http://dx.doi.org/10.1176/appi.psy.51.4....
,3232 Sleath B, Chewning B, de Vellis BM, Weinberger M, de Vellis RF,
Tudor G, et al. Communication about depression during rheumatoid arthritis
patient visits. Arthritis Rheum. 2008;59(2):186-91,
http://dx.doi.org/10.1002/art.23347.
http://dx.doi.org/10.1002/art.23347...
). Therefore, it is
imperative to implement a standard care process that identifies those groups with a
higher predisposition for developing depression in an effort to provide early
referral to psychiatric treatment.
With respect to the correlates of depression, the findings from the multivariate
analysis indicated that age is positively correlated with the risk of depression.
One possibility is that older RA patients have other age-associated functional
declines that might aggravate their psychological distress. However, this result is
inconsistent with findings reported in 3 other studies (1313 Margaretten M, Barton J, Julian L, Katz P, Trupin L, Tonner C,
et al. Socioeconomic determinants of disability and depression in patients with
rheumatoid arthritis. Arthritis Care Res. 2011;63(2):240-6,
http://dx.doi.org/10.1002/acr.20345.
http://dx.doi.org/10.1002/acr.20345...
,1414 Rivero-Carrera NN, Serra-Bonett N, Snih SA, Duque-Criollo JV,
Rodríguez MA. Risk factors associated with depressive symptoms in
Venezuelan patients with rheumatoid arthritis. J Clin Rheumatol.
2011;17(4):218-9,
http://dx.doi.org/10.1097/RHU.0b013e31821c7af3.
http://dx.doi.org/10.1097/RHU.0b013e3182...
,3333 Margaretten M, Yelin E, Imboden J, Graf J, Barton J, Katz P, et
al. Predictors of depression in a multiethnic cohort of patients with rheumatoid
arthritis. Arthritis Rheum. 2009;61(11):1586-91,
http://dx.doi.org/10.1002/art.24822.
http://dx.doi.org/10.1002/art.24822...
). Such conflicting findings may be due to
differences among the participants and designs of the various studies. For example,
the participants in the latter studies were Westerners, who may have been more open
to discussing psychiatric disorders. This openness could possibly have lessened or
moderated the effect of age on the risk of depression. Furthermore, most prior
studies were conducted using a cross-sectional design that made it difficult to
reach clear conclusions. The retrospective cohort-controlled design employed in our
study allowed us to make more reliable conclusions concerning the relationship
between age and depression among RA patients.
Our study revealed that females are 1.78-fold more likely to suffer from depression
than males, which was consistent with the findings of previous reports (1212 Murphy LB, Sacks JJ, Brady TJ, Hootman JM, Chapman DP. Anxiety
and depression among US adults with arthritis: prevalence and correlates.
Arthritis Care Res. 2012;64(7):968-76.,3030 Margaretten M, Julian L, Katz P, Yelin E. Depression in patients
with rheumatoid arthritis: description, causes and mechanisms.
Int J Clin Rheumatol. 2011;6(6):617-23.).
A possible reason for this finding is that women have been shown to be more
health-conscious than men and more likely to pursue treatment at the earliest sign
of medical irregularity (3434 Minh HV, Byass P, Chuc NT, Wall S. Gender differences in
prevalence and socioeconomic determinants of hypertension: findings from the WHO
STEPs survey in a rural community of Vietnam. J Hum Hypertens.
2006;20(2):109-15, http://dx.doi.org/10.1038/sj.jhh.1001942.
http://dx.doi.org/10.1038/sj.jhh.1001942...
), thus increasing
the probability of detecting depression. Our results, however, are inconsistent with
those of other studies showing only a marginally increased rate of depression in
female RA patients (2020 Sato E, Nishimura K, Nakajima A, Okamoto H, Shinozaki M, Inoue
E, et al. Major depressive disorder in patients with rheumatoid arthritis. Mod
Rheumatol. 2013;23(2):237-44,
http://dx.doi.org/10.3109/s10165-012-0643-8.
http://dx.doi.org/10.3109/s10165-012-064...
,3232 Sleath B, Chewning B, de Vellis BM, Weinberger M, de Vellis RF,
Tudor G, et al. Communication about depression during rheumatoid arthritis
patient visits. Arthritis Rheum. 2008;59(2):186-91,
http://dx.doi.org/10.1002/art.23347.
http://dx.doi.org/10.1002/art.23347...
). The contradictory results in these former studies may be
due to the low statistical power resulting from small sample sizes, with only 113
and 200 participants recruited per study.
Regarding the effect of comorbidity on the risk of depression, the present study showed that RA patients with certain comorbidities, including chronic kidney disease, stroke or cancer, have a significantly greater risk of depression. RA patients with hypertension, diabetes mellitus and heart disease showed a tendency to develop depression, but the association failed to reach statistical significance. Despite the lack of comparative studies on the effects of comorbidities, our findings are, nevertheless, in agreement with arguments made in the literature (3030 Margaretten M, Julian L, Katz P, Yelin E. Depression in patients with rheumatoid arthritis: description, causes and mechanisms. Int J Clin Rheumatol. 2011;6(6):617-23.) suggesting that comorbidities among RA patients may be associated with a predisposition for developing depression. We speculate that the comorbidities accompanying RA might negatively affect the patients' perceptions of their health status or reduce their ability to withstand therapy-induced side effects and other complications stemming from their condition, thus leading to a higher risk of depression. Furthermore, a recent review article reported that depressive mood may be related to the types of drugs a patient receives such as oncologic medications, corticosteroids or biological agents (3535 Celano CM, Freudenreich O, Fernandez-Robles C, Stern TA, Caro MA, Huffman JC. Depressogenic effects of medications: a review. Dialogues Clin Neurosci. 2011;13(1):109-25.). Therefore, clinicians are encouraged to carefully appraise the effects of a medication prior to using it to treat RA patients with depression. This approach could be beneficial in reducing the risk for depression following an RA diagnosis.
The following limitations merit consideration when considering the findings of this
study. First, we did not account for other confounding factors such as the use of
tobacco and alcohol, physical activity, body mass index, social networks, religious
beliefs and educational level because they were unavailable in the LHID.
Accordingly, caution must be exercised when interpreting this study's findings.
Nonetheless, a meta-analysis of the depression risk estimate in RA found that RA per
se could predict a predisposition toward depression through the activation of
pro-inflammatory cytokines (2929 Malemud CJ, Miller AH. Pro-inflammatory cytokine-induced
SAPK/MAPK and JAK/STAT in rheumatoid arthritis and the new anti-depression
drugs. Expert Opin Ther Targets. 2008;12(2):171-83,
http://dx.doi.org/10.1517/14728222.12.2.171.
http://dx.doi.org/10.1517/14728222.12.2....
). Nonetheless,
future studies using more specific covariates are recommended to assess whether the
present findings can be replicated among other demographically and geographically
diverse groups. In addition, the relationship of depression prognostic outcomes
among RA patients should be considered. Second, inaccurate diagnoses may have
occurred. To minimize this error, we selected subjects with RA or depression only
after they were recorded to have at least 2 outpatient visits reporting consistent
diagnoses or one inpatient admission. Furthermore, the Taiwan NHI randomly samples
claims from hospitals, interviews patients and reviews medical charts to verify the
accuracy of medical records. Third, as data regarding RA severity were not available
in this claims database, failure to adjust for this factor might have biased the
results. However, the multivariate analysis applied considered the impact of several
comorbidities with physical impairments, including hypertension, stroke, DM, heart
disease, CKD and cancer. Furthermore, we conducted a sensitivity analysis limited to
RA subjects without comorbidities and found that these patients with RA still had a
significantly higher incidence rate and aHR of depression (11.51
vs. 6.49 per 1000 PYs; aHR: 1.78). Thus, the impact of disease
severity is unlikely to compromise the results of this study. Despite these
methodological concerns, this population-based, retrospective cohort study provides
useful information on the relationship between RA and the subsequent risk of
depression among Chinese patients.
In conclusion, this study demonstrates that the RA patients evaluated were 1.74 times more likely to be diagnosed with depression than the general population after adjusting for several potentially influential covariates. The factors leading to an increased risk of depression among RA patients included being female and older, as well as having certain comorbidities such as stroke, chronic kidney disease and cancer. The data from this population-based study allow healthcare providers to further understand the demographic and disease characteristics that may provoke depression among RA patients. The need to routinely observe patients for signs of depression and to institute culturally appropriate interventions should be emphasized.
ACKNOWLEDGMENTS
The study is based in part on data from the National Health Insurance Research Database provided by the Bureau of National Health Insurance, Department of Health and managed by National Health Research Institutes. The interpretation and conclusions contained herein do not represent those of the Bureau of National Health Insurance, Department of Health or the National Health Research Institutes. This research was supported by Buddhist Dalin Tzu Chi Hospital (Grant Number DTCRD102-I-04). MCL, HRG, MCL and HL contributed equally to this work.
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No potential conflict of interest was reported.
Publication Dates
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Publication in this collection
Feb 2015
History
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Received
20 Aug 2014 -
Reviewed
29 Sept 2014 -
Accepted
5 Dec 2014