Vinod Chandran, MBBS, MD, on Depression, Anxiety, and Psoriatic Arthritis

Vinod Chandran, MBBS, MD, is director of the Psoriatic Arthritis Research Program at the University Health Network at the University of Toronto, Toronto, Ontario, Canada. He sat down with us to talk about his research into the impact of depression and anxiety on patients with psoriatic arthritis and how that can reduce the chances of achieving minimal disease activity.

Rheumatology & Arthritis Learning Network:  Thank you for joining us today, Dr Chandran. What led you to undertake this study of the impact of depression and anxiety on achieving minimal disease activity among patients with psoriatic arthritis?

Dr Chandran: As you know, psoriatic arthritis is an inflammatory arthritis associated with psoriasis, which is another chronic inflammatory condition. On average in North America, about 3% of the population has psoriasis, and we believe about 25%, a quarter of them, have a specific form of inflammatory arthritis called psoriatic arthritis. As you can imagine, when you have a chronic skin condition that is likely to be associated with stigma and mental health issues, and then on top of it, when you have an arthritis which causes pain and is associated with more inflammation, you can have more issues with your mental health, with anxiety and depression.

And there is research which showed a relationship between depression and particularly psoriasis, much less in psoriatic arthritis, but in psoriasis, it's been shown that people with psoriasis are more likely to be depressed, and people who are depressed are more likely to get psoriasis. So, there is a bidirectional relationship.

We did a study some time ago where we showed that the prevalence of anxiety and depression was also quite high in patients with psoriatic arthritis and more than just patients with psoriasis without the arthritis. So, depression and anxiety or mental health issues are a significant comorbidity in patients with psoriatic disease. It’s an important challenge that we struggle to manage as we see patients with psoriatic disease.

So we know the prevalence. The question we had, in this particular study, was how does that impact improvements of the disease status, so-called minimal disease activity, and does that influence it? Are people with anxiety and depression less likely to reach that state? We didn't go into mechanisms, but this was the first step of trying to see if there was a relationship between the mental health issues and actually feeling better.

RALN:  You mentioned the prevalence. What is the prevalence of depression/anxiety as a comorbidity among these patients?

Dr Chandran: Studies show that it's quite high. Our own study, from I think about 2014, where we use questionnaires, it was about 20%, 25%. If you put anxiety and depression together, it's about 30%, depression, 20%, anxiety, 35%. So, quite a high prevalence, and that's been shown in other jurisdictions also.

RALN: You used 3 different tools to assess for depression among the patients that you included in your study. One was the mental health component summary of the medical outcome study short form, or the SF-36, the mental health domain of the SF-36 Health Survey, and a rheumatologist report of a diagnosis or treatment for depression or anxiety. Why did you choose these multiple methods of assessment?

Dr Chandran: The biggest challenge in assessing mental health, anxiety, and depression is proper diagnosis. Ideally, if we are working closely with a mental health team, we could get a psychiatrist to evaluate and then see how that impacts long-term treatment. Unfortunately, that was not possible, due to various reasons—resource constraints in particular.

What we do in our program, is see patients in a longitudinal cohort, so we see patients at least once every 6 months, even if they're doing really well, so that we get both a good picture and the entire spectrum of how people are doing. And at each of these visits, patients fill up a questionnaire, and that includes this Short-Form 36, which provides us with various scores on the mental health as well as physical. We've been doing that for quite a long time. We began in the ‘90s, so we have a longitudinal information, which has been quite useful.

In our clinic assessment, we do ask the patient if they've been diagnosed with anxiety and depression and, if so, what treatments they're on. So, we have multiple sources of information, using the questionnaires, and there was a study from Europe where they use these questionnaires, and therefore there was a precedent on using the mental health components as well as the summary score to define anxiety/depression. That's why, if you look at the paper, we don't say anxiety/depression separately because it's a mix of that, so not a proper diagnosis. The only diagnostic thing that we had was our note, based on the assessment by the patient reporting a diagnosis, either by the family physician or a psychiatrist, as well as if they were on treatment.

So, we had 3 different sources, primarily because we didn't have a gold standard. As you would see in the paper, consistently, the 3 methods of assessment provide us with a similar kind of result, which hopefully validates it. This was a study, using our data, and now, I hope, we and others could formally evaluate all our patients, at least at baseline and whenever there are significant changes in the health status, to kind of document that.

RALN: How did you define minimal disease activity for the purposes of your study?

Dr Chandran: The goal of treatment of psoriatic disease is remission, and ideally drug-free remission, which might be very difficult to achieve, but even with treatment, we like to achieve remission. Now, the question is, what is remission? How do you define it?

Given the current state of affairs, we don't have a perfect drug. There's always some amount of disease activity, meaning there's persistent inflammation after you use any of the traditional or advanced therapies. There is a concept of minimal disease activity, which basically indicates, given the current circumstances or resources available, the lowest level of disease activity that can be achieved.

Laura Coates, a friend and colleague from the University of Oxford, when she was a trainee at the University of Leeds in the United Kingdom, developed the criteria for defining somebody to be in a state of minimal disease activity. Now, there are 7 criteria, and you have to achieve 5 of the 7 to say you are at the state of minimal disease activity. And Laura had gone forward and done studies, using that as a target, to show that if you try to treat patients to that target, the target of minimal disease activity, which is not perfect, but still better than what we have, you get more likely to get patients into a better response over time. There is less joint damage when we reach that state.

But what is accepted is the 5 out of 7, which can be easily done in routine clinical practice, which evaluates not just the joints, but also the skin. And so that was used as the criteria, and we were also interested it being sustained. So, in our cohort, we record this every 6 months. We said, "Just one off is not good enough. We need it for at least 2 visits, so at least 6 months." We said, "In 2 consecutive visits, if you're in MDA, if you satisfy these criteria, then you're in sustained MDA."

RALN: So you set out to determine if depression or anxiety is associated with achieving or not achieving sustained minimal disease activity in patients with psoriatic arthritis. What did you find?

Dr Chandran: I wouldn't say that I was surprised, but what I found, and therefore confirmed—obviously we need further studies also— that whatever definition of anxiety/depression that we use, it was associated with a significantly less likelihood of achieving the state of sustained minimal disease activity. We also looked at various other factors, what treatment they were on, obviously, demographic factors, age, gender, amount of damage that was had, their social circumstances, etc.

We found that defining anxiety and depression, it didn't matter what definition that we used, there was more than 50% lower chance of achieving minimal disease activity, which was, I wouldn't say surprising, but at least we documented that. There were other studies in Europe that found a similar finding, and so this tells us that we really need to take that into account when we manage our patients.

RALN: That's a high number, 50% of these patients, who are probably not sustaining or achieving minimal disease activity because of, or at least in the presence of, depression or anxiety. The question is—and you mentioned this earlier when you said it was bidirectional—is there a way to determine if the depression is caused by the challenges of having a chronic illness, or was the depression pre-existing? Does it complicate treatment? What, if anything, did you find out about that? Was that clarified at all in your study?

Dr Chandran: Not in our study. In our cohort, we analyzed data that we collected over the years, and defined patient depression. We said, "we'll look for what happens to them once they have that, not clearly diagnosis, but when they're classified as having that, what happens to their response?" And this was about our management, not specifically to any particular drug or anything, but how when they're in a clinic and when we manage them according to current guidelines. So, what we found was that, if you are depressed, you're less likely to achieve that status.

Now, going back to your question about the relationship between depression and psoriatic disease, previous research, not ours, have shown the relationship being bidirectional. So if you have the condition, you're more likely to have depression, over time, and that we attributed to the chronic inflammation, the stigma of the skin disease, the chronic pain that one suffers from, when we have the arthritis. And the other way around, whether presence of depression itself leads to these conditions, has been shown in studies like the Nurses' Health Study, where patients who were classified as depressed in this large database that was analyzed, and they, over time, saw that those who reported more depression had more psoriasis, down the line. Once you have psoriasis, you're also more likely to get psoriatic arthritis, although that's a bit more of a challenge, and therefore, we don't have large studies, but I presume that depression would also predispose to the arthritis.

We have a study which looks longitudinally at developing arthritis in patients with psoriasis. So, we recruit patients without arthritis, but who have psoriasis, and look in the long-term. We don't have that many converters, as we call them, at the moment— converters meaning progressing from psoriasis to psoriatic arthritis—but when we have enough numbers, and there are other studies going on worldwide, we'd have a better idea. But I would not be surprised if they are more likely to develop psoriatic disease, and we get that signal from psoriasis. There's a bidirectional relationship, and the question is, if you treat depression/anxiety better, are you going to have less psoriasis and psoriatic arthritis in the future? We don't really know that. It's important to recognize this important comorbidity.

RALN: But that's going to be one of the questions you look at — if you treat this effectively, does that help reduce the amount of depression and anxiety among those patients?

Dr Chandran: Yeah. There's been a concern, especially in psoriasis trials, where patients with psoriasis have a high risk of suicide. Now in clinical trials, there have been suicides, and although the numbers are very small, in some of the drug trials there was an imbalance. And as the patients feel better, the skin gets better, their scores improve, and we would expect mental health issues, suicidality, to go down, but it's not been very clear. Some drugs have a warning, and before putting patients on those drugs, we'd say, "Well, clinical trials do show that there might be a problem. And so, the mood changes, best to stop the drug and let us know." We counsel patients appropriately. We still have a lot more to learn about the relationship with these drugs and mental health. Generally speaking, things improve, but not everybody's the same. Things may go in the opposite direction for some.

RALN: Your study is very much in line with other things that are going on in rheumatology, where there seems to be an increasing emphasis in identifying mental and emotional conditions, such as depression and anxiety, among patients and finding ways to help patients who have these conditions. What might you recommend to clinicians as methods to assess patients' emotional and mental health in a clinic visit, when their time is so often limited, and they're looking for efficient ways to identify these patients who are at risk of developing worsening depression and anxiety? What would you say to those people?

Dr Chandran: Clinicians are busy, and when you look at from the whole-body perspective, it's been a challenge. And what we need to do is to at least ask that question. I know your skin is bad, or your joints are hurting—how are you otherwise feeling? And many times, that, it gives the patient a relief that somebody is concerned about it, especially when we feel that the skin and joints are actually better, but why is the patient not feeling better?

If you're working in a large university setting, hopefully there are channels where you can direct the patients to the appropriate department for evaluation. Most of us work closely with the primary care practitioner, who have more of a skill set in managing this, and so at least make a clinical note to the primary care practitioner, mentioning that this might be an issue, which is obviously impacting quality of life. Questionnaires and all that, in a busy practice, I don't think is very useful. When I talk with dermatologists, we have questionnaires for screening for arthritis, they say, “We are overwhelmed.” Primary care physicians are also overwhelmed, but at least asking the question takes the first step. When I speak to patient organizations, the biggest concern they have is about fatigue and mental health rather than the number of swollen joints or tender joints, when we ask about what matters to them. And so, even if the doctor does not ask you, bring it up so that it is addressed.

RALN: Any final thoughts or advice for your colleagues in rheumatology on working with patients with psoriatic arthritis, who may be showing depression and anxiety?

Dr Chandran: I would ask them, as you ask for joint pain and how the skin is, also ask, "How are you feeling?" Just that simple question might open a big window for having a frank conversation. This is an important comorbidity. We talk a lot about cardiovascular disease and try to control inflammation to prevent heart disease. This is also another important comorbidity.

RALN: Thank you very much for spending this time with us today. It's been very helpful.