Addressing Psychiatric Comorbidities in Inflammatory Rheumatic Diseases

Although physiologic effects such as pain, stiffness, and swelling are among the hallmark symptoms of rheumatoid arthritis (RA), an increased prevalence of psychiatric disorders has also been noted in individuals with RA compared with the general population.¹ A study published in 2010 identified arthritis as a risk factor for the subsequent development of a mental health disorder (odds ratio [OR], 1.94; 95% CI, 1.23-3.07), especially among patients <45 years of age.²

Depression and anxiety are commonly observed psychiatric disorders in this patient population. In a large meta-analysis published in 2013, the prevalence of major depressive disorder was 16.8% among individuals with RA, and up to 48% of participants experienced subclinical depression.³ A 2010 study reported that the lifetime prevalence of anxiety disorders was 16% among patients with RA.⁴

Other findings have linked mental health comorbidities with worse outcomes pertaining to pain, disability, and health-related quality of life in people with RA.^5,6 In addition, depression is associated with decreased treatment adherence and reduced treatment response and rates of remission in RA.^7-10

To learn more about psychiatric comorbidities in RA, including underlying mechanisms and clinical implications for rheumatologists, Rheumatology Advisor interviewed psychologist John A. Sturgeon, PhD, assistant professor, Department of Anesthesiology and Pain Medicine at the University of Washington School of Medicine in Seattle. He co-authored a comprehensive review on the topic, which was published in 2016 in Nature Reviews Rheumatology.¹

Rheumatology Advisor: What is known about mental health comorbidities in RA?

Dr Sturgeon: The best way to summarize the relationship between mental health conditions and RA is that they are mutually influential. People with RA show higher rates of certain mental health disorders, most notably major depressive disorder and certain anxiety disorders (panic disorder and generalized anxiety disorder). Conversely, there does not appear to be strong evidence that mental health disorders can cause or increase the likelihood of the onset of RA.

However, the presence of symptoms of depression and anxiety can worsen RA symptom severity, cause poorer response to medical treatment for RA, and can increase the likelihood of other health problems in RA such as heart attacks and suicide. Depression, in particular, can make it hard for people with RA to follow the medical recommendations made by their doctors about appropriate treatment, which can worsen the response to treatment and worsen RA disease processes in the future. 

Similar patterns have been found for people with RA and posttraumatic stress disorder (PTSD), such that the presence of PTSD symptoms seems to be a factor that can contribute to worsened RA symptoms such as pain and fatigue. The body of research examining the interaction of PTSD and RA processes is still quite small, however, and these effects haven’t been borne out in a large number of studies yet.

Interestingly, there appears to be a reduced level of prevalence of schizophrenia in people with RA compared with the broader population. Although the research base on this is relatively small and we aren’t sure of the exact mechanisms connecting them, it appears that there may be some aspects of the pattern of inflammatory processes that occur in RA that may make the occurrence of schizophrenia less common. This may be the result of factors such as differences in certain genes, side effects of long-term medication use for RA or schizophrenia, or differences in stress response, although it isn’t entirely clear at present.

Rheumatology Advisor: What are the proposed physiologic mechanisms involved in the link between RA and psychiatric disorders?

Dr Sturgeon: There are several factors that appear to connect RA and mental health disorders. One is inflammation — it is well-documented that RA is a disease defined by abnormal inflammatory processes in the brain and body, but there is also mounting evidence that there may be altered inflammatory pathways for people with major depressive disorder.

Some research has found that the body’s central stress system, the hypothalamic pituitary adrenal axis, is significantly altered in people with RA, including changes in communication between the hypothalamic pituitary adrenal axis and other parts of the nervous system and changes in how stress hormones are circulated in the body.

We aren’t yet sure what role these altered immune system and inflammatory processes play in the intersection between depression and anxiety and RA, however. At this point, it just appears to be a possible connecting link suggesting altered brain function in both RA and mental health processes that may be a useful target for future research and intervention. It is reasonable to state, however, that stress is a likely contributor to these issues.

People with chronic medical conditions like RA do show changes in their responses to stress, both in terms of the body’s physical response and their psychological responses. There is also some evidence from other chronic conditions that involve chronic pain — such as low back pain and fibromyalgia — that the brain’s reward processing areas may be altered in part through their communication with stress and inflammatory processes, but this has not been studied in RA specifically.    

Rheumatology Advisor: What are the psychological mechanisms believed to underlie the association between RA and mental health disorders?

Dr Sturgeon: People with RA who experience stronger negative reactions to stress or pain in terms of their emotions or thoughts appear to be more vulnerable to depression and anxiety and also appear to be at greater long-term risk for disability as a result of RA. The presence of depression or anxiety is a fairly strong predictor of more intense negative emotions in response to stress and can increase the likelihood that an individual will view a stressor in his or her life as a particularly catastrophic event, which can worsen the emotional consequences of stress.

When people experience these more intense negative emotions or thoughts in response to a stressor like pain or other physical symptoms, it can make it harder for them to respond in a healthier way, which worsens the entire process.

As an example, responding to pain or stress by either isolating yourself or avoiding anything that causes pain or stress is a long-term risk factor that can worsen mood, physical functioning levels, and overall disease activity. Unfortunately, these patterns are more likely in people who experience high levels of depressive or anxious symptoms, or in people with high pain and fatigue. 

As a psychologist, I tend to think of behavior as one of the most meaningful mechanisms in determining health and disease treatment outcomes. There are usually factors — such as exercise, diet, stress management, or following up on medical recommendations — that can be targeted to improve the severity of a disease.

When psychological factors such as poor mood, low motivation, or low social support interfere with these behaviors, the physical symptoms can be made worse. It is certainly reasonable to state that the effect works in reverse, as well — the severity of physical symptoms can worsen mood and disrupt healthy behavior. Our goal, then, is to break this unfortunate cycle of pain, fatigue, poor mood, and unhealthy behavior.

Rheumatology Advisor: How should rheumatologists address these issues in clinical practice?

Dr Sturgeon: One of the key findings that has emerged from the literature is that there are a significant number of patients with RA who also experience depression. However, studies suggest that important issues such as depression and fatigue are only discussed in a minority of appointments with rheumatologists, which can leave these issues unaddressed and untreated. Given that adherence with medical treatments such as disease-modifying antirheumatic drugs may decrease when patients are dealing with significant issues of depression, it is important to implement at least a basic screening for depression, such as the Patient Health Questionnaire-9, a basic screening for anxiety, such as the Generalized Anxiety Disorder-7, and a basic screening for PTSD, such as the Primary Care PTSD Screen.

These questionnaires are free online, easy to administer (a total of 20 questions between all 3 instruments), have scores that are easy to interpret, and can be a useful tool in talking to patients about their mental health. More broadly, I would urge rheumatologists to consider screening and treatment of mental health as a necessary part of RA care. Spending time talking with patients about both their physical symptoms and their mood symptoms can improve not only the working relationship between a patient and their doctor, but also can help identify other symptoms that may interfere with effective RA treatment and improve the overall quality of life in people with RA. 

It is also useful to urge patients to participate in their care to the maximum extent possible, such as maintaining regular exercise, good dietary habits, effective stress management techniques, and pursuing good social support and social interactions. One useful resource to consider is the Chronic Disease Self-Management Program originally developed by Dr. Kate Lorig at Stanford. These classes are typically very low-cost and can be found in many communities. A geographically based search for these programs can be found here.

The CDC also provides a good informational webpage on this topic that I recommend. There are other effective treatments for mental health in RA, including cognitive-behavioral therapy and mindfulness-based stress reduction. Mindfulness-based stress reduction instructors can be found through the following website.

Rheumatology Advisor: What are some of the remaining research needs regarding this topic?

Dr Sturgeon: There are several remaining areas of research that may be useful in further expanding our understanding of the overlap between RA and mental health. As I mentioned, researchers have found altered signaling in the reward processing areas of the brain, particularly involving transmission of dopamine. We suspect that this altered neural signaling process could be a risk factor for mood disturbance and less healthy behaviors in people with RA, but it has only been observed in other chronic medical conditions with significant rates of pain, such as fibromyalgia or chronic back pain.

From a clinical standpoint, building better models of effective detection and treatment of depression in RA may do quite a bit to improve the quality of RA care. There have also been calls for many years to focus additional research on fatigue as an important indicator of RA disease activity. Fatigue is also common in disorders like depression and anxiety and can be related to factors like sleep disturbance, inflammation, and medication use. In many cases, fatigue is also a strong predictor of the level of physical function that people with RA report in research studies.

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References

1. Sturgeon JA, Finan PH, Zautra AJ. Affective disturbance in rheumatoid arthritis: psychological and disease-related pathways. Nat Rev Rheumatol. 2016; 12(9):532-542.
2. van ‘t Land H, Verdurmen J, Ten Have M, van Dorsselaer S, Beekman A, de Graaf R. The association between arthritis and psychiatric disorders; results from a longitudinal population-based study.J Psychosom Res. 2010;68(2):187-193.
3. Matcham F, Rayner L, Steer S, Hotopf M. The prevalence of depression in rheumatoid arthritis: a systematic review and meta-analysis.Rheumatology (Oxford). 2013;52(12):2136-2148.
4. Lok EYC, Mok CC, Cheng CW, Cheung EFC. Prevalence and determinants of psychiatric disorders in patients with rheumatoid arthritis. Psychosomatics. 2010;51(4):338-338.e8.
5. Rupp I, Boshuizen HC, Roorda LD, Dinant HJ, Jacobi CE, van den Bos G. http:Poor and good health outcomes in rheumatoid arthritis: the role of comorbidity. J Rheumatol. 2006;33(8):1488-1495.
6. Löwe B, Willand L, Eich W, et al. Psychiatric comorbidity and work disability in patients with inflammatory rheumatic diseases.Psychosom Med. 2004;66(3):395-402.
7. DiMatteo MR, Lepper HS, Croghan TW. Depression is a risk factor for noncompliance with medical treatment: meta-analysis of the effects of anxiety and depression on patient adherence.Arch Intern Med. 2000;160(14):2101-2107.
8. Kekow J, Moots R, Khandker R, Melin J, Freundlich B, Singh A. Improvements in patient-reported outcomes, symptoms of depression and anxiety, and their association with clinical remission among patients with moderate-to-severe active early rheumatoid arthritis. Rheumatology (Oxford). 2011;50(2):401-409.
9. Hider SL, Tanveer W, Brownfield A, Mattey DL, Packham JC. Depression in RA patients treated with anti-TNF is common and under-recognized in the rheumatology clinic. Rheumatology (Oxford). 2009;48(9):1152-1154.
10. Rathbun AM, Reed GW, Harrold LR. The temporal relationship between depression and rheumatoid arthritis disease activity, treatment persistence and response: a systematic review.Rheumatology (Oxford). 2013; 52(10):1785-1794.