The burden of depression in patients with rheumatoid arthritis
An ever‐increasing body of research confirms that rheumatoid arthritis (RA) is associated with depression. Conservative estimates using research interviews, the gold standard of psychiatric assessment, place the prevalence of depression in this patient group in the region of 13–20% depending on the sociodemographic and disease characteristics of the population studied (proportion of females, severity and chronicity of illness etc.) [1, 2]. Thus, RA patients are twice as likely to suffer from depression as members of the general population. In RA patients, depression not only contributes its own additional burden but also interacts with the way patients perceive and cope with their physical illness and how they interact with their rheumatologist and general practitioner. Thus, depression increases the burden of RA to the patient and society.
Studies investigating the nature of the interaction of depression with the symptoms, cognitions and behaviours of RA patients offer some insight into why RA patients get depressed and what impact this depression has on their physical state. Depression in RA patients is associated with increased levels of pain . This association has been shown to remain significant (Pearson’s r=0.46) even after the degree of disease activity has been controlled . Depression has been shown to be associated with more graphic verbal descriptions of the type of pain (e.g. excruciating), though not with the reported frequency of pain . There is much argument as to whether depression simply reflects a reaction to the pain of RA  or whether depression contributes to the pain experience . The majority of studies in this area have been cross‐sectional in design, allowing no causal inferences to be drawn. Longitudinal studies are few and throw no light on the causal relationships between pain and depression [8–11]. Studies in other groups with chronic musculoskeletal pain, however, indicate that the causal relationship between pain and depression may act in both directions, with pain increasing depression and depression increasing pain .
Depression is also associated with increased functional disability in RA patients. Longitudinal studies have shown that depression occurs following deterioration in functional ability, particularly with regard to activities which an individual regards as being important, e.g. visiting the family, going away on holiday. A 10% reduction in ability to perform these valued activities is followed by a seven‐fold increase in depression over the subsequent year . However, depression also precedes increases in disability , predicting poorer functional status, more disability days and more RA‐related hospitalizations . Furthermore, reduction in disability has been shown to follow improvement in depression in medical patients, though such changes are yet to be shown in RA patients specifically . Thus, the causal association between depression and disability may act in both directions also.
The mechanisms by which pain and disability may lead to depression are unclear. Certainly pain and disability are potent stressors and may increase the likelihood of depression. However, the large number of patients who experience severe pain and disability but do not report depression suggests that other factors are important. There is evidence to indicate that the pain and disability of RA are insufficient in themselves to cause depression, except in advanced disease . Social factors, such as social stress and lack of social support, have been shown to be highly associated with depression in RA . Thus, the pain and disability of RA may only precipitate depression when they are severe enough to contribute to social stresses (such as financial difficulties) and to limit the patient’s activity enough to reduce their access to social support. More research is needed to examine the inter‐relationships between these variables if causal associations are to be clarified.
The mechanisms by which depression influences pain and disability are also poorly understood. Though depression and psychological stress have been shown to result in immune dysfunction , there is no evidence to suggest that depression increases the pain and disability of RA by changing the underlying inflammatory activity. Studies suggesting that depression increases disease activity, or that psychological treatment reduces RA activity have relied on clinical assessments of disease activity, such as counting tender joints . Such clinical assessments rely on patient reports of tenderness and are vulnerable to the effects of depression and the associated, negative way patients react to their illness. There is, as yet, no evidence that depression alters laboratory markers of disease activity, though this mechanism cannot be ruled out.
The way RA patients think about their illness is crucial to understanding the association of depression with pain and disability. Depression is associated with increased worry about illness and conviction of severe disease , and this association remains even when the extent of disease and pain levels are controlled . Depressed RA patients perceive their illness as being more serious and feel hopeless about a cure compared with non‐depressed RA patients, even when the actual severity of arthritis is adjusted for . Depression is associated with impairment of general coping, especially at high levels of pain . It is also associated with impaired coping for flare‐ups of the disease .
As the result of these negative illness beliefs, depression is likely to affect health‐seeking behaviours and healthcare utilization as it does in other medical patients [25–27]. Depressed RA patients are more likely to report physical symptoms , less likely to be reassured by a doctor  and, surprisingly, less likely to comply with medication . We know there is immense variation in costs between subjects which is not directly related to the severity of RA [29, 30]. Depression is likely to contribute to these hitherto unexplained costs. The impact of depression on indirect (social) costs is likely to be even greater . It is not surprising then that Parker and Wright suggested a bio‐psycho‐social approach to the management of RA . They recognized that, though the costs of depression in RA were high, depression is a treatable condition with good expectations of treatment in two‐thirds of subjects.
Yet depression remains mostly unrecognized and undertreated in these patients. This is partly attributable to a tendency to focus on the physical aspects of disease coupled with limited resources. The problem of undertreatment of depression in RA is exacerbated by the misconception that, because depression is understandable, occurring secondarily to the pain and disability, treatment of the depression is not appropriate or necessary . Furthermore, diagnosing depression in patients with RA is complicated as there is an overlap of the symptoms of depression and RA (e.g. fatigue, weight loss, insomnia and lack of appetite) such that the depression frequently goes unrecognized . Use of standardized psychiatric questionnaires (Minnesota Multiphasic Personality Inventory, the Beck Depression Inventory and the Center for Epidemiologic Studies Depression Scale) tends to overestimate the prevalence of depression as many include somatic symptoms which may be attributable to RA [4, 34]. Scales which have little somatic content, such as the Geriatric Depression Scale , the Hospital Anxiety and Depression (HAD) scale  and disease‐specific instruments , may aid the accurate diagnosis of depression in persons with RA, though some follow‐up questioning is required to determine whether intervention is necessary.
Lack of familiarity with antidepressant drugs may also contribute to the undertreatment of depression. There is a wide choice of antidepressants currently available to clinicians, yet the majority of these drugs have not undergone efficacy assessment in patients suffering from physical illness. Current evidence from studies in psychiatric and other chronic pain populations indicates that major groups of antidepressants, i.e. tricyclics (TCAs) and specific serotonin re‐uptake inhibitors (SSRIs), when given in appropriate psychotherapeutic doses, have roughly equal efficacy in the treatment of depression .
These groups do differ in their analgesic efficacy, tolerability and profile of drug interactions, however. TCAs with the least specific receptor activity, such as amitriptyline, appear to have the greatest analgesic efficacy , even at low doses (e.g. 25 mg of amitriptyline) and independently of whether depression is present . In higher doses tolerability is poor, particularly in old age, and hence compliance suffers. Drug interactions occur, though this is not a problem with first‐ and second‐line treatments for RA. SSRIs are generally much better tolerated, though they have less analgesic effect than TCAs. Their lack of affinity for histamine H1, muscarinic or α1‐adrenergic receptors results in fewer serious side‐effects, though they can cause nausea, diarrhoea and impaired sexual functioning [41, 42]. Newer drugs have comparable efficacy as antidepressants, though their analgesic efficacy is yet to be established and they are more expensive.
In general SSRIs, such as fluoxetine or citalopram, in doses up to BNF maxima should be considered as first‐line treatment for depression in RA . Gradually introduced TCAs, such as amitriptyline and dothiepin, should be used in low doses (25–75 mg) for pain relief . Combined use of TCAs and SSRIs greatly increases the risk of adverse events and should be avoided unless under expert guidance .
In conclusion, RA affects 0.5% of the adult population of the UK . Thus, by conservative estimates, approximately 200000 adults suffer from the pain and disability of this condition. As many as 40000 of these will suffer from depression, two‐thirds (27000) of whom would respond quickly to an antidepressant . Adequate treatment of the depression in this group could be achieved with minimal extra costs. The benefits are likely to be greatest in those with the most advanced disease. For these reasons it is crucial that we place more emphasis on the detection and treatment of depression in RA to improve function and quality of life in this patient group.
C. Dickens and F. Creed
Department of Psychological Medicine, University of Manchester, Oxford Road, Manchester, UK
Correspondence to: C. Dickens, School of Psychiatry and Behavioural Sciences, Rawnsley Building, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL, UK.
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