Introduction

Polymyalgia rheumatica (PMR) is a common inflammatory musculoskeletal condition of older (>50 years) adults, which classically presents with bilateral hip and shoulder girdle stiffness, often associated with raised inflammatory markers, which typically responds well to low-dose glucocorticoids, the mainstay of treatment [1]. Other inflammatory rheumatic disorders, such as rheumatoid arthritis, are associated with an increased prevalence of depression [2], which negatively impacts on a number of outcomes including treatment response [3], quality of life and mortality [4].

Given the inflammation associated with PMR, its associated pain and disability and the long-term nature of the condition [1], it seems likely that people with PMR are more likely to experience depression. Treatment with glucocorticoids may also have a bidirectional effect on depression, for although glucocorticoid treatment itself is associated with depression [5], their effectiveness at controlling inflammation and reduction of PMR symptoms [6] means that they may in fact have a positive impact on depression in PMR patients.

Several studies have investigated the prevalence of depressive symptoms in patients with PMR, with reported rates varying from 2 to 29% [7,8,9,10,11,12] depending on the method of ascertainment of depression used, which varied from clinical interview [7, 8] to medical record review [9,10,11]. However, the majority of studies were small (ranging from 17 to 129 participants) and were based in secondary care settings, limiting the generalisability of these studies to the wider PMR population due to the highly selected nature of these populations. A single study used a patient-reported questionnaire (the SF-36 Mental Component Score (MCS), which is validated for assessing mental distress) [12] to ascertain depression, and found that PMR patients at initial presentation had significantly lower mean MCS scores (indicating a worse emotional quality of life) than older age (65–74 years) population norms (scores 38.9 versus 53.2), although this had improved significantly at 12 months. To date, factors associated with depression in patients with PMR have not been investigated. The aim of this study was to investigate the prevalence of, and factors associated with, depressive symptoms in primary care PMR patients.

Materials and methods

Study design and population

A cross-sectional questionnaire study was developed to investigate the impact of PMR in primary care patients. Adults with a first Read coded diagnosis of PMR in the last 3 years (since 1 January 2010) were identified via an electronic search of the primary care records of the 150 participating general practices from across England. The relevant PMR Read code used was N20. The lead general practitioner (GP) from each practice screened the list of identified patients and removed those in potentially vulnerable groups (e.g. with significant cognitive impairment), those under 50 years of age (since PMR is rare and often atypical in those under 50) and those with a first PMR diagnostic Read code before 1 January 2010. Remaining eligible participants (n = 704) were mailed a questionnaire including socio-demographics (age, gender and personal circumstances), PMR characteristics (duration and current symptoms), current glucocorticoid use and presence of comorbidities that may relate to glucocorticoid use (e.g. diabetes and hypertension) using a yes/no checklist. Non-responders to the mailed study pack were sent a reminder postcard at 2 weeks and a repeat study pack at 4 weeks to optimise response. Ethical approval for the study was obtained from NRES-West Midlands-Staffordshire (Ref 13/WM/0133).

Presence of depressive symptoms was assessed using the Patient Health Questionnaire-8 (PHQ-8), which is validated for assessing depression in a primary care population [13]. Each of the eight items assesses symptoms during the preceding 2 weeks and is scored on a 4-point scale from 0 (not at all) to 3 (nearly every day). The total PHQ-8 score ranges from 0 to 24 points with higher scores representing more severe depressive symptoms [14]. For a descriptive summary of depressive symptoms, previously validated cut points for symptom classification of severity of depressive symptoms were used [14], with a score 0–4 denoting no depressive symptoms, 5–9 mild depressive symptoms, 10–14 moderate depressive symptoms, 15–19 moderately severe depressive symptoms and 20–24 denoting severe depressive symptoms. For other purposes, a dichotomised measure indicating more broadly the presence of depressive symptoms was used as a PHQ-8 score of ≥10, which has previously been used by Kroenke et al. [13] to describe current depressive symptoms in the general population.

Statistical analyses

The age and gender of the responders and non-responders to the questionnaire were compared using t test and chi-squared tests respectively to assess for evidence of responder bias. All subsequent analyses were performed only on those who had reported ever using glucocorticoids for their PMR, as a way of validating the GP diagnosis of PMR, as not to have received glucocorticoids would be atypical.

Frequencies and percentages were used to summarise categorical variables and mean (standard deviation) and median (interquartile range (IQR)) to summarise age and time since PMR diagnosis, respectively. Logistic regression models were used to obtain estimates of association between demographics, PMR characteristics and self-reported comorbidities and current depression. Results are presented as odds ratios (ORs) and associated 95% confidence intervals (CIs). Variables with significant crude association with depression and those deemed clinically relevant a priori (i.e. age and gender) were included in a multivariable logistic regression model to estimate adjusted associations with depression. Primary analyses were performed on patients with complete data only; however multiple imputation by chained equations [15], using 20 imputations, was used to impute missing data. All analyses were subsequently re-performed to assess for any sensitivity due to missing data. All analyses were performed using STATA version 12 (StataCorp).

Results

Of the 704 participants who were mailed a questionnaire, 550 (78%) responded. One hundred six participants did not respond and 48 declined participation in the study. Figure 1 indicates the flow diagram of participants. The non-responders and refusals (n = 154) did not differ significantly from the responders in terms of age (mean (SD) 75.2 (9.2) versus 74.2 (8.4), p = 0.21) or gender (n = 112 (73%) versus n = 365 (66%) females, p = 0.14). Those who did not report ever taking glucocorticoids for their PMR or who had missing data for this variable (n = 25, 4.5%) were excluded from subsequent analyses.

Fig. 1
figure 1

Flow diagram of participants

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Demographics and prevalence of depression

The baseline characteristics of the 525 complete responders used in the analysis are summarised in Table 1. The mean (SD) age was 74.1 years (8.4), and 346 (66%) were female. Median (IQR) disease duration was 2.3 years (1.5–3.2), and 332 (64%) were currently still taking glucocorticoids. Depressive symptoms were common, with 81 (15%) patients classified as having current depressive symptoms (PHQ-8 score >10), of whom half (41/81, 50.6%) had moderate symptoms and only (9/81, 11%) were classified as having severe symptoms (Table 1). Those with depressive symptoms were more likely to be female (OR 1.87 (1.09–3.22)) and of younger age (OR for 80+/70–79/60–69-year-olds versus 50–59-year-olds were 0.35, 0.36 and 0.38, respectively). Presence of depressive symptoms was significantly associated with reporting current PMR symptoms (OR 2.1 (1.11–3.97)). An association was demonstrated between depressive symptoms and current glucocorticoid use though significance was not achieved (OR 1.29 (0.76, 2.19)) (Table 2). Those reporting potential glucocorticoid-related comorbidities including GI problems (such as acid reflux), diabetes and osteoporosis were also more likely to report depression, although no association was seen with presence of giant cell arteritis or other major comorbidities such as heart disease or stroke. Table 3 gives the results of the multivariable model that included all the variables that had a significant crude association with depression. Only diabetes remained significantly associated with current depressive symptoms (OR 4.1 (2.01–8.37)). No difference in findings was observed following multiple imputation (data not shown, results available from authors on request).

Table 1 Baseline characteristics
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Table 2 Unadjusted associations of patient characteristics with depression
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Table 3 Multivariable modela: adjusted associations of patient characteristics and depression
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Discussion

This study found that depressive symptoms are common in primary care PMR patients, occurring three times more commonly than in the general older adult population (4.9%) [14]. Those with current PMR symptoms were more likely to report depressive symptoms, although no significant association was observed between current glucocorticoid use and depression.

Depressive symptoms were commoner in younger patients with the odds of reporting depression declining with age. This is in contrast to the relationship found between age and depression in the general elderly population, where the prevalence of depression increases with increasing age [16, 17]. The higher prevalence of depressive symptoms in the younger PMR patients could in part be explained by the impact of PMR on physical functioning; it may be that younger patients, who may still be in employment or be more physically active, may be affected more by their PMR and hence more likely to report depression.

Depression was commoner in women, as is the case in the general population [17]. However, the rates of depressive symptoms observed in our study were significantly higher than those observed in older (>65) females (5.9%) [18] without PMR supporting the hypothesis that PMR itself is associated with depression.

A number of factors may help to explain this increased prevalence of depression in PMR patients. Firstly, PMR is an inflammatory condition [1] and studies have found that inflammation (via interleukin-6 (IL-6) and C-reactive protein (CRP)) is associated with the development of depressive symptoms [19]. Secondly, long-term glucocorticoid treatment is associated with depression [5], although if treatment leads to better symptom control it may reduce depressive symptoms [20]. In this study, no association was seen between current glucocorticoid use and depressive symptoms, although depressive symptoms were commoner in those still reporting PMR symptoms. The single study to investigate the long-term impact of PMR on mental health found significant improvement at 12 months [12], supporting the importance of current PMR symptoms on depression, especially given that pain and disability are associated with depression in the general population [21, 22]. Further prospective studies are required to elucidate the relationship between PMR symptoms, glucocorticoids and depression in patients with PMR.

Studies have observed that patients with chronic conditions in primary care have twofold to threefold increases in rates of depression compared to age- and gender-matched controls [23,24,25]; thus, the chronic nature of PMR may contribute to the increased reporting of depression. Within this study, some comorbidities, such as diabetes, were associated with increased depression prevalence, although other comorbidities, such as heart disease and stroke, were not. A recent meta-analysis suggested [25] found that depression is nearly twice as common in people with diabetes compared to those without, although other studies suggest this association is weaker in older (>60 years) people [24] and as such is unlikely to explain our findings.

There are several strengths and weaknesses that need to be considered when interpreting the results of this study. This was a large cohort of PMR patients recruited from across England, with depression measured using the PHQ-8, a validated highly sensitive and specific depression measure for primary care patients [13], which is also validated for rheumatology patients [26], and as such, the results are likely to be highly generalisable. A limitation is that these patients had a primary care diagnosis of PMR, rather than having been assessed in specialist services. The American College of Rheumatology (ACR)/European League against Rheumatism (EULAR) Classification Criteria illustrate the difficulties in accurately diagnosing PMR even by specialists, with 10 out of 128 (7.8%) PMR patients later having their diagnosis changed [27]. Nevertheless, the demographics of this population are similar to those seen in both primary [28] and secondary care PMR cohorts [12], and patients not reporting glucocorticoid use were later excluded to further validate the GP diagnosis of PMR and provide further confidence in the accuracy of our results.

In summary, depressive symptoms are common in PMR patients particularly in those that are younger, female and with comorbidities such diabetes. As PMR is primarily diagnosed and managed in primary care, this suggests GPs should be aware of this association and could consider screening for depressive symptoms in these patients as this may improve their quality of life.