Study Examines How Depression Subtypes May Stem from Osteoarthritis

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People with or at risk for sympto­matic knee osteoarthritis (OA) may be assigned to four depression subtypes with distinct clusters of depressive symptoms that may affect pain and disability over time, according to a new study in Arthritis Care & Research.¹

Four depression subtypes were identified in the study using the Center for Epidemiologic Studies Depression scale—catatonic, anhedonic, melancholic and asymptomatic—that could one day drive treatment optimization for patients, says co-author Alan M. Rathbun, PhD, MPH, a research associate at the University of Maryland School of Medicine, Baltimore. The study was supported by the Rheumatology Research Foundation’s Scientist Development Award.

“Knee OA is clinically heterogeneous, like depression, and is characterized by ‘the disease’ and the ‘illness,’ corresponding to the structural pathology of the joint and patients’ experience of symptomology, respectively,” says Dr. Rathbun, whose research was inspired by his chronic perseverative stuttering and associated social anxiety. “Knee OA progression may cumulatively contribute to psychosocial impairment over time. Prior studies have not recognized the potential contributions of structural pathology to the development of depression, or that this process aggregates and isn’t confined to a finite period of time.”

Dr. Rathbun

As many as 20% of people with osteo­arthritis experience depression and anxiety symptoms, according to a 2016 meta-analysis, and research also shows that knee pain, impaired function and depressive symptoms are all associated.^2,3 Dr. Rathbun co-authored a 2017 study that showed depressive symptoms are significantly associated with disease progression.⁴

Pain severity significantly increases with the persistence of depression in patients with knee OA, according to his recent research.⁵ However, Dr. Rathbun feels these connections are not well understood. The new study examined how depression subtypes may stem from OA disease severity.

Study Highlights

The study’s 4,486 participants were part of the Osteoarthritis Initiative, a multi-center observational cohort study of both men and women sponsored by the National Institutes of Health (NIH). All had baseline symptomatic knee OA data and baseline radiographs read by certified technicians at Boston University.

The researchers applied latent class analy­sis (LCA) to the 20-item Center for Epidemiological Studies Depression Scale measured at baseline to identify groups with similar patterns of depressive symptoms, and then assigned subtypes to each participant using poster probability estimates. Relationships between depression subtypes and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and disability subscales were modeled over four years and stratified by baseline knee OA status; 1,626 patients had symptomatic knee OA, and 2,860 patients were at risk.

When grouped into the four subtypes, 80.6% of participants were asymptomatic, 5.3% were catatonic, 10.6% were anhedonic and 3.5% were melancholic. Patients in the catatonic subtype expressed symptoms of psychomotor agitation. Those in the anhedonic subtype had symptoms associated with the inability to experience pleasure. Those in the melancholic subtype expressed symptoms related to reduced energy and movement, anhedonia and other somatic complaints. Some overlap exists, a consequence of the subtypes also correlating to differences in depression severity (a potential way to discern groups), in which a greater number and spectrum of symptoms equates to greater burden.

When researchers compared subtype characteristics, the catatonic and melancholic group members were more likely to be female, nonwhite, not married and of lower socioeconomic status compared with those in the asymptomatic group.

Associations were generally greater in those with symptomatic knee OA compared to at-risk participants. Among those with symptomatic knee OA, only the melancholic group had persistently greater pain and disability during the follow-up. When compared to the asymptomatic group, both the catatonic and anhedonic groups had small differences in pain and disability from baseline (≤1 rescaled WOMAC unit).

The results showed greater differences in pain between the melancholic and asymptomatic groups. These increased from 0.47 (95% confidence interval [CI]: -3.86, 4.62) at baseline to 4.79 (95% CI: -1.77, 11.35) at the fourth annual follow-up visit. Participants in the melancholic group also had increases in disability over four years, rising from 2.80 (95% CI: -1.84,7.44) at baseline to as much as 6.56 (95% CI: 1.72, 11.40) rescaled WOMAC units during the follow-up period.

Recognition of, and treatment for, specific depression subtypes remain a ways off, according to Dr. Rathbun. He says, “Nonetheless, our results highlight the potential spectrum of depressive symptomology in patients with musculoskeletal disorders, and interventions could be designed in such a way that they target both knee OA and depression—all potential phenotypes—simultaneously, rather than considering each condition in isolation as a uniform collection of symptomologies.”

Patients with certain depression subtypes may respond differently to various treatments, Dr. Rathbun says. “For example, antidepressants could have high efficacy for treating symptoms related to anhedonia, but not be particularly effective with respect to psychomotor agitation, which is perhaps more aptly addressed with exercise training.”

Simple Screening Tools

The study highlights the need for simple depression screening tools in routine rheuma­tology clinical practice, says Dr. Rathbun. The Patient Health Questionnaire-2 (PHQ-2) is one widely used tool. It poses two questions scored on a scale of 0 (not at all) to 3 (nearly every day):

Questions: Over the past two weeks, how often have you been bothered by the follow­ing problems?

1. Little interest or pleasure in doing things.
2. Feeling down, depressed or hopeless.

A score of three or higher is a cutoff point for depression. A more in-depth version includes nine questions.

Ms. Batterman

The Hospital for Special Surgery, New York, screens all rheumatology patients at intake and, when appropriate, triggers referrals to mental health services, says Adena Batterman, MSW, LCSW, a senior manager in the Inflammatory Arthritis Support and Education Programs.

“As part of a comprehensive psychosocial assessment, social workers screen patients for all issues that may impact your ability to cope with a rheumatic disease,” says Ms. Batterman. “There are many barriers to effective screening, especially in inflammatory arthritis, because many depression symptoms are the same as rheumatoid arthritis: sleep problems, pain and fatigue. It’s difficult to tease out what’s due to RA [rheumatoid arthritis] and what to depression.”

As in OA, depression is highly prevalent in patients with RA and associated with worse disease outcomes.⁶ Other conditions treated by rheumatologists also have high rates of depressive symptoms and depression. For example, more than 80% of patients with fibromyalgia had clinically significant depressive symptoms in a 2011 study, and their depressive symptoms were associated with higher pain perception and worse quality of life.⁷ Patients with systemic lupus erythematosus (SLE) were six times more likely to have depression than healthy controls in a 2018 study.⁸

“There is a surprisingly low incidence of rheumatologists asking about these issues in medical encounters,” says Ms. Batterman. In a 2008 study, only 19% of RA patients whose screening indicated they had moderately severe to severe depression symptoms discussed depression during their medical visits, and the patients brought it up, not the provider.⁹ “It’s important to make this screening part of a normal exam routine because of the profound impact of depression on RA disease outcomes. It’s all a part of treating the person as a whole.”

Dr. Chan

Barriers to effective depression screening and referral in rheumatology include short appointments and a lack of clear clinical directives about mental health, says Karmela Kim Chan, MD, a rheumatologist at the Hospital for Special Surgery. She says PHQ-2, while brief, is a useful first step.

“There are no treatment guidelines on mental health along the lines of treat to target, for example. But it is very important,” she says. Psychological symptoms “may alter a patient’s subjective scores for pain or fatigue, so it definitely plays a role in clinical decision making. I won’t shy away from bringing up mental health issues with my patients. Instinctively, we know that when we’re treating someone with a rheumatic disease, there may be a mental health component. It’s important not to forget about this.”

Stamp Out Stigma

In Southern California, the Loma Linda University Medical Center’s rheumatology clinic gives all patients a standard mental health questionnaire, says Vaneet Kaur Sandhu, MD, an associate program director. Positive results alert the rheumatologist to ask more questions and refer to a mental health provider if indicated.

“[Although] these tools are certainly helpful, I find really just interacting with patients to be most effective,” says Dr. Sandhu. “I set goals for each patient appointment to include a meaningful interaction, one in which I feel I have connected somehow with the patient. In establishing a relationship with patients, I feel an added benefit, so that if something is missed during our mental health screening, perhaps we can address [it] during the clinic visit.”

Mental health issues are not being adequately addressed in rheumatology or anywhere else in healthcare, she says.

“The first and most important barrier to mental healthcare is the social stigma that must be stamped down,” says Dr. Sandhu. “I’m often frustrated that a patient of mine cannot see a psychiatrist because their insurance will not cover it, or that it will be months before the patient can be seen. This is not acceptable. We need more resources, at the very least, to triage patients and act as a bridge to established mental healthcare.”

Rheumatology clinics should try to screen patients for depression as early in the care continuum as possible, according to Dr. Rathbun. “The gravity of this task,” he says, “is immensely challenging, but at the end of the day, [it] may be reliant on regular communications between patients and providers, such as brief, candid and routine inquiry, and discussion of patients’ mental health status during clinical encounters.”

Susan Bernstein is a freelance journalist based in Atlanta.

References

1. Rathbun AM, Schuler MS, Stuart EA, et al. Depression subtypes in persons with or at risk for symptomatic knee osteoarthritis. Arthritis Care Res (Hoboken). 2019 Apr 5.
2. Stubbs B, Aluko Y, Myint PK, et al. Prevalence of depressive symptoms and anxiety in osteoarthritis: A systematic review and meta-analysis. Age Ageing. 2016 Mar;45(2):228–235.
3. Sugai K, Takeda-Imai F, Michikawa T, et al. Association between knee pain, impaired function and development of depressive symptoms. J Am Geriatri Soc. 2018 Mar;66(3):570–576.
4. Rathbun AM, Yau MS, Shardell M, et al. Depressive symptoms and structural disease progression in knee osteoarthritis: Data from the Osteoarthritis Initiative. Clin Rheumatol. 2017 Jan;36(1):155–163.
5. Rathbun AM, Stuart EA, Shardell M, et al. Dynamic effects of depressive symptoms on osteoarthritis knee pain. Arthritis Care Res (Hoboken). 2018 Jan;70(1):80–88.
6. Matcham F, Rayner L, Steer S, et al. The prevalence of depression in rheumatoid arthritis: A systematic review and meta-analysis. Rheumatology (Oxford). 2013 Dec;52(12):2136–2148.
7. Aguglia A, Salvi V, Maina G, et al. Fibromyalgia syndrome and depressive symptoms: Comorbidity and clinical correlates. J Affect Disord. 2011 Feb;128(3):262–266.
8. Figueiredo-Braga M, Cornaby C, Cortez A, et al. Depression and anxiety in systemic lupus erythematosus: The crosstalk between immunological, clinical and psychosocial factors. Medicine (Baltimore). 2018 Jul;97(28):e11376.
9. Sleath B, Chewning B, de Vellis BM, et al. Communication about depression during rheumatoid arthritis patient visits. Arthritis Rheum. 2008 Feb 15;59(2):186–191.