The underrated prevalence of depression in Japanese patients with rheumatoid arthritis - evidence from a Nationwide survey in Japan

Significant evidence in the scholarly literature suggests that depression is a common comorbidity among patients with rheumatoid arthritis (RA) [1–3]. The prevalence of depression varies significantly between different studies, but by some estimates occurs in as many as 42% of RA patients [4]. A meta-analysis of 72 studies involving 13,189 people with RA revealed that from 14.8 to 38.8% of people with RA receive a diagnosis of a major depressive disorder [5].

Depression in RA is a risk factor not only for suicidal ideation [6] but for cardiovascular disease [7], myocardial infarction [8], and mortality [9]. Patients with RA are at greater risk of experiencing anxiety, depression, and low self-esteem, with higher levels of associated mortality and suicide [10]. It was suggested that nearly 11% of people with RA experience suicidal thoughts, a statistic that rises to an alarming 30% in patients with a co-morbidity of depression [11]. Previous study found that people with comorbid RA and depression may use more health services and are less likely to adhere to their medication regimens [12, 13]. A comorbidity of RA and depression is also associated with higher unemployment, work productivity losses, and increased healthcare costs to both individual patient and society [13, 14].

More often than not comorbid depression with RA is undiagnosed and therefore untreaeted [15] often because rheumatologists and their patients seldom communicate about depression [13, 16]. In the USA and Europe, the prevalence of depression was high in people with RA and the prevalence was found to be greater in younger patients [5]. Similar findings were found in only one Japanese study that identified factors associated with depression in female people with RA and found that among sociodemographic factors, “a decrease in the frequency of going out socially after having RA” and “a higher education” were significantly associated with depression [17]. However, evidence of depression in people with RA is limited in Asia studies and also Japan.

The present study was undertaken to determine the prevalence of depression in Japanese People with RA and explore the relationships between RA patient, depression and an array of demographic variables.

The results of this study reveal that one third of Japanese people with RA might potentially have depression as assessed by PHQ-9 while only 5% are officially diagnosed. Additionally, younger, less educated, more functionally impaired patients, and patients who are being treated with csDMARDs alone are more likely to have depressive syptoms. These findings are important to increase awareness of rheumatologist regarding depression. Furthermore, the results call for multidisciplinary treatment teams that do not only focus on the treatment of physical symptoms but also take into account a patient’s psychological condition. This approach will bring together the skills and knowledge of all team members which may may comprise case managers, pharmacists, physical and occupational therapists, social workers, physiatrists, orthopedists, or other health professionals to assess and manage care for the individual patient’s needs [22].

The key finding of this study is that a potential significant under-reporting of depression among Japanese people with RA might exist. The prevalence of depression among people with RA has been reported in previous studies worldwide [5], ranging from 15% up to 39%, and our finding of 35% by PHQ-9 is consistent with those results. Severe depressive symptom (PHQ ≥ 10) was less frequent in this study (11%) than the frequency reported in Asians and Pacific Islanders reported in 2009 (36%), which might be due to the development of treatment along with less physical functional impairment. However, there was still discrepancy in the prevalence between PHQ-9 and the official diagnosis. One explanation of the under-reporting of depression might be related to Asian cultural factors. People in Asian societies such as China and Japan are less likely to speak openly about depression due to the stigma attached to it as well as the need to maintain perceived strength of character [23]. However, differences in prevalence can be found when using different measurement instruments. For example, the point prevalence of major depressive disorders in Japanese people with RA was 6.8% when using the Mini-International Neuropsychiatric Interview [24]. This observation makes it the more important for physicians and all healthcare professional who are members of multidisciplinary team in Asia to be highly attuned to potential depression when treating their people with RA.

In this study, people with comorbid RA and depression tended to be younger than people without depression. This comparison is evident as well in the national Japanese survey conducted by the Ministry of Health, Labor, and Welfare in 2014 [25] and an Japanese employee survey conducted by the Northern-Japan Occupational Health Promotion Centers Collaboration Study for Mental Health [26]. Additionally, the results of the present study showed a positive association between depression and migraine and heart condition comorbidities. Several studies reported the relationship of depression with cardiovascular disease [27, 28], which is well known to be correlated with RA [29, 30].

Several studies show a positive correlation between depression and RA disease activity scores such as disease activity score for 28-joint (DAS28) or clinical disease activity index (CDAI) [31, 32]. Although the current study did not measure disease severity by such composite measures due to the limitations of online survey, people with RA were asked to rate their functional disability using J-HAQ [18], which closely correlates to both DAS28 and CDAI [33]. The results indicate that a higher J-HAQ score was correlated with depression. J-HAQ can measure a variety of functional limitations caused not only by inflammatory disease activity but also by joint damage and long-term disability. The resulting loss of valued activities has been shown to be a strong predictor of depression in patients with RA [13, 34]. Additionally, systemic inflammation that also causes functional disability is associated with, causes, or contributes to depressive symptoms experienced during the course of disorders that include chronic inflammation [35]. Patients with major depression have increased Interleukin 6 (IL-6) [36]. concentrations and pro-inflammatory tumor necrosis factor-alpha (TNF-α) [37] in serum, plasma, or both. A recent meta-analysis showed raised inflammatory markers such as IL-6 or C-reactive protein (CRP) are significantly associated with the subsequent development of depressive symptoms, which supports the hypothesis that there is an association between the inflammation and depression [38]. Consequently, medications that result in lower IL-6 and TNF-α level might have a direct positive impact on treating depression. Our findings also showed that patients receiving biologic agents had lower probability of developing depression compared to patients treated with csDMARDs alone, which can also be explained by the mechanism of the reduction of cytokine level that might be linked to depression [38–40]. These findings suggest that further research on the connection between biologic treatment and depression is needed.

There were several limitations to the present study. First, the analysis was based on a cross-sectional survey. As this was a single sample, the study was unable to demonstrate a causal relationship or account for changes in perception that might occur over time. Second, the study did not show that the documented depression condition was the direct consequence of the patient’s RA condition – other factors in patients’ lives could be the cause. Third, the exact disease activity was not completely known because this was an online survey consisting of patients reports. This hampered the analysis for the direct relationship between disease activity and depression. Furthermore, this was an online survey which might not be representative of the overall Japanese RA population. Usually, people that are more familiar with the Internet take part in online surveys which are in turn younger and probably better educated. On the other hand, the average age of our sample (54.28 years) does not differ much from a recent Japanese claims database analysis with more than 16,000 RA patients [41]. In that study the average patient age was 53.96 years which makes us believe that the potential selection bias in our sample is low. Last, there is a possibility of diagnostic overshadowing if some physical symptoms of RA are misattributed to depression. An example is feeling tired or having little energy which are both symptoms of depression as well as RA. This can potentially lead to an overestimation of depression in RA.

In conclusion, the results of this study suggest that depression among Japanese people with RA is potentially under-reported and under-diagnosed. Rheumatologists should take particular care in assessing the psychological status of people with RA, particularly those susceptible to depression –younger patients, patients with greater functional impairment, and patients with a treatment regimen of csDMARDs alone.