Depression and Fatigue in Rheumatoid Arthritis-

A Study in Southern India

Emily James, Suseem Sundaram, Renjitham*

School of Advanced Sciences (SAS), Vellore Institute of Technology (VIT), Vellore.

*Corresponding Author E-mail: emilyjames2001@gmail.com, srsuseem@vit.ac.in

ABSTRACT:

Rheumatoid Arthritis is a chronic autoimmune condition in which the patient experiences pain, joint immobility which in some instance can also lead to disability, and thus difficulty in carrying out various activities of daily living. It is a natural consequence that patients may experience varying degrees of depressive symptoms and fatigue. Aim and Objectives: In our study, it is our objective to find out the prevalence of depression, its severity and its correlation with disease activity, pain and inflammatory markers like ESR. We also attempted to quantify the fatigue using the MAF scale by calculating the GFI (Global Fatigue Index) and its prevalence in remission vs non remission patients. Study design: The study is a cross-sectional observational study of consecutive patients with a diagnosis of RA as per EULAR 2020 criteria. The patients were interviewed using standard questionnaires MAF (multidimensional assessment of fatigue questionnaire) and PHQ9 (Patient Health Questionnaire 9). Tools used in the study: Fatigue was measured by using MAF (Multidimensional Assessment of Fatigue). Depression is measured using the PHQ9 questionnaire. Results: The population studied was found to have a prevalence of 33.5% depression. The patients’ mean age was 52.45±10.53 years and disease duration 8.02±6.22 years. Their mean DAS28 was 2.96±1.1. The mean PHQ-9 score was 3.99±3.5., mild (26%), moderate (5.5%), moderately severe (1.5%) and severe (0.5%) degrees. Correlation of PHQ9 scores with DAS, VAS and ESR was done to see if there is a relation of depression to any of the clinical outcomes. It was found that depression had a positive correlation with disease activity score DAS 28 (coefficient of correlation 0.167, p = 0.018), VAS pain scores (coefficient = 0.361, p < 0.001) as well as ESR (coefficient = 0.217, and p = 0.002).

Fatigue was evaluated using the MAF which gave the Global Fatigue Index (GFI). The mean MAF score was 8.62±3.33. 78% of patients had fatigue in the level (0-10), 20.5% in the (10-20) level and 1.5% in the (20-30) level. Statistical test for comparison between groups using t test was found to be significant with p value 0.034.

Conclusion: Our study on both depression and fatigue once again emphasises the need for rheumatologists especially in the Indian scenario to address them in their routine clinical practice. There should be regular screening for these conditions during the patient visits similar to other risk factors screening in RA.

KEYWORDS: Patient Health Questionnaire, Global Fatigue Index, Multidimensional Assessment of Fatigue, remission, correlation.

INTRODUCTION:

Arthritis is a chronic auto immune disorder characterized by pain, swelling and stiffness. Rheumatoid arthritis affects approximately 1% of the population worldwide. Its etiology is still unknown.¹ Depression can affect anyone and it is one of the most widespread illnesses, often co-existing with other serious illnesses like arthritis.

Depressive disorders can start even at a young age; they reduce people’s functioning and can be recurring.²

Fatigue is reported rarely and treatment options or strategies of management are discussed infrequently. Many physicians consider fatigue a ‘standard norm’ of the treatment or disease, on which nothing can be done, and hence to be endured.³

Depression and fatigue are reported by a majority of the RA population and could be due to a number of factors. However, both often go unrecognised or unaddressed in the management of the disease. Indeed, even though many potential outcome measures were considered in the series of international meetings that developed the core set, fatigue is not mentioned at all^4.Yet, fatigue and depression can have subtle but overwhelming effects on the quality of life of patients suffering from it.

Recent OMERACT meetings have brought to the notice of the physicians the effect of fatigue and its implications in the lives of RA patients and as a consequence fatigue is now included as one of the core outcome measures for patients with RA along with pain and morning stiffness.⁵

FATIGUE:

Fatigue in RA has not been fully understood. Chronic pain, coexisting affective disorders like depression, cognition problems and sleep disorders again seen commonly in the RA population could be a contributive factor to the fatigue experienced. The circulating cytokine abnormalities and high inflammatory markers is one among many causes postulated to be the underlying pathology for the condition. Patients experiencing severe fatigue also are found to have higher disease activity and higher pain levels. Among the two, fatigue has often shown stronger correlation with pain than disease activity.⁶ A systematic review by Nicholaus et al⁷ found possible causes of fatigue in illness-related aspects, physical functioning, cognitive/emotional functioning, and social aspects. Another review by Zielinski MR has reported a relationship between types of fatigue and certain brain areas, cell types, and phenotypes that mediate the symptoms observed. Consequently, immunomodulatory agents and drugs targeting inflammatory pathways could serve to treat fatigue occurring in autoimmune and related diseases.⁸

Untill now, management of fatigue in RA has not been a priority of rheumatologists. Treatment of underlying disease activity correlates with fatigue relief. Exercise programmes and supervised self-management programmes with cognitive-behavioural therapy, mindfulness and reinforcement reminders⁹which have shown to be beneficial in fatigue management should be incorporated into the patient care of the RA patient.

Possible consequences of fatigue were also found among illness-related aspects, physical functioning, cognitive/emotional functioning, and social aspects.

DEPRESSION:

Seen commonly in RA patients could also be associated primarily with the chronic pain experienced by the patients. Several studies report that baseline depression and anxiety levels in RA are associated with decreased likelihood of achieving remission,^10,19,20 although others have not found this. There appears to be a complex interplay between depression and RA, with shared inflammatory pathways postulated.¹¹ Notably, Schrepf et.al have demonstrated how chronic inflammation in RA has an impact on the brain.¹² Higher peripheral inflammation was consistently correlated with neural connectivity patterns, particularly inferior parietal lobe and medial prefrontal cortex over a 6-month period. Unrelieved pain affects all dimensions of quality of life.¹³ RA induced disability, interference in activities of daily living can also affect the psychosocial life of the patient and can account for the depression.

SIGNIFICANCE:

Management of fatigue whether in Rheumatoid Arthritis or other chronic conditions like cancer is evasive. Fatigue does not always improve with improvement in disease activity and may exist quite prominently in absence of functional disability or even during normal disease outcome. In Rheumatoid Arthritis treatment of the underlying inflammatory condition using TNF inhibitors has been found to have a beneficial effect on fatigue. Depression can affect the quality of life of the patients, cause complications like sleep and eating disorders and also lead to suicidal ideology in most severe cases. With earlier diagnosis and aggressive treatment, many individuals can lead a decent quality of life.^14. It is important that rheumatologists are aware of the impact of depression on the lives of their patients. Rheumatologists should be able to identify patients prone to both these conditions and intervene early to have a beneficial outcome.

AIM AND OBJECTIVES:

In this study, we have attempted to study the prevalence of depression among the RA study population and to judge its severity using the PHQ9 (depression) and MAF questionnaires.

Further, we aimed to correlate the severity of depression and fatigue with age of the patient, duration of illness, disease activity scores (DAS 28 ESR), VAS (pain) scores and ESR values using Pearson’s correlation test. Additionally, a comparison on fatigue experienced by remission v/s non remission patient was also attempted. The objective here was to analyse the GFI scores obtained by patients in remission for prevalence of fatigue and compare with GFI levels in non-remission patients.

STUDY DESIGN:

The study is a cross-sectional observational study of consecutive patients with a diagnosis of RA as per EULAR 2020 criteria. The PHQ9 (Patient Health Questionnaire 9) questionnaire in depression and MAF (multidimensional assessment of fatigue) questionnaire in fatigue were used as the tools for assessment. Patients unwilling to attempt either of these questionnaires due to the length or personal nature of questions or any other reason were excluded from this study. Incomplete responses were also rejected. Hence the final number of completed respondents was 200.

ETHICAL CONSIDERATIONS:

Ethical approval was obtained prior to the onset of the study (VIT/IECH/006/April16, 2016). The patients were selected based on an inclusion exclusion criteria and informed consent was obtained.

TOOLS USED IN THE STUDY:

Fatigue was measured by using subjective measures using questionnaires like MAF (Multidimensional Assessment of Fatigue). The MAF questionnaire measures fatigue based on 4 criteria: 1) Severity 2) Distress 3) Effect on Activities of Daily Living (ADL) and 4) Timing. It gives the GFI or global fatigue index which is the total score obtained as sum of the 15 items scored. Depression is measured using the PHQ9 questionnaire and is based on the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) diagnostic criteria and it allows measuring the mood of the patient in the weeks prior to consultation.¹⁵ Erythrocyte Sedimentation Rate (ESR) test is a blood test conducted to detect the presence of arthritis. Normal ESR (mm/hr) = Age (in years) + 5 (if female). Higher values indicate inflammation as in RA or other interpretations.^16.VAS (visual analogue scale) is a scale on 0-10 with no pain taken as 0 and pain level graded upto 10. DAS (Disease Activity Score) ESR is used to measure the severity of disease and scores range from remission score less than 2.6 and higher grades indicating higher severity of disease.

Table 1: Analysis of the severity of depression in the population.

Level of Depression (PHQ-9)	Frequency	Percent
Minimal	133	66.5 %
Mild	52	26 %
Moderate	11	5.5 %
Moderately severe	3	1.5 %
Severe	1	0.5 %
Total	200	100 %

RESULTS:

1) Depression:

The population studied was found to have a prevalence of 33.5% depression. The patients’ mean age was 52.45 ±10.53 years and disease duration 8.02±6.22 years, 90.5% were females and 9.5% males (F:M 9.5:1). Such a female predominance is well established in rheumatoid arthritis in other studies.^17,18. Their mean DAS28 was 2.96±1.1. The mean PHQ-9 score was 3.99±3.5. 33.5% of patients had depression; mild (26%), moderate (5.5%), moderately severe (1.5%) and severe (0.5%) degrees.

Fig 1: Categories of Disease activity

Fig 2. Patient categories of pain by VAS scale

Fig 3. Scatter plot correlation between PHQ 9 and DAS 28 (ESR.)

Fig 4. Scatterplot correlation between PHQ 9 and VAS

PHQ-9 is significantly correlated with DAS-28 (coefficient = 0.167, p = 0.018).PHQ-9 is significantly correlated with VAS (coefficient = 0.361, p < 0.001).

The population was also categorised based on clinical outcomes like disease activity scores using DAS 28 (ESR), VAS(pain) and ESR values.

1. The mean DAS-28 score was 2.96±1.1. 60% of patients had disease; low disease activity (23.5%), moderate disease activity (33%), and severe disease activity (3.5%).

2. VAS- pain. The mean VAS score was 3.01±2.16. 92% of patients had pain; mild pain (60%), moderate pain (29%), and severe (3%).

Next correlational studies using scatter plot were carried out to find relation between PHQ9 depression scores with DAS28, VAS and ESR.

Fig 5. Scatterplot correlation between PHQ 9 and ESR.

PHQ-9 is significantly correlated with ESR (coefficient = 0.217, p = 0.002).

2) Fatigue:

Table 2: Distribution based on fatigue severity using MAF GFI scores.

Fatigue (MAF)	Frequency	Percent
0-10	156	78 %
10-20	41	20.5 %
20-30	3	1.5 %
Total	200	100 %

Table 3. Categorisation of remission and nonremission patients according to MAF GFI scores

Fatigue	Disease Activity
	Remission (Cure)		Non-remission
	f	%	f	%
0-10	66	42.3%	90	57.7%
10-20	13	31.7%	28	68.3%
20-30	1	33.3%	2	33.3%

Our next objective was to find if there was a significant difference in the fatigue frequency in remission vs the non- remission population. Remission patients were categorised based on DAS 28 (ESR) score less than 2.6.

Statistical test for comparison between groups using t test was found to be significant with p value 0.034. Thus fatigue experienced by remission group significantly differs from the non- remission group.

DISCUSSION AND CONCLUSION:

Depression is one of the common comorbidities in rheumatoid arthritis. It affects the quality of life of the affected and can interfere with their daily activities. In our study we have tried to study the prevalence of depression in our patient population. Previous reports have shown that there is a frequency range of 13% - 56% of depression in the RA population using various tools of measurement.^19,20 Arthritis can also compromise the quality of life of patients in addition to producing such a psychological impact.²¹ Our study showed a prevalence of 33.5 % depression. We also evaluate the severity of depression experienced by the RA patients using the PHQ-9 questionnaire. Majority of the population studied suffered from minimal (66.5%) to mild (26%) depression. Less than 10% of the population had a higher grade i.e. moderate to severe depression and only 1 patient showing severe depression. Item wise analysis of the response shows that disturbance in sleep and eating patterns was the most common among the symptoms experienced by the patients with depression. Also decrease in energy levels and a slowness in movement was reported by a sizeable population. Suicidal ideation was an extremely rare symptom. Hence we can conclude that depression was a bothersome symptom which interfered with the patients daily routine and compromised their quality of life. However major depressive disorder with suicidal ideation was an extremely rare condition. This warrants the need for counselling the patients for depression. Correlation with DAS, VAS and ESR was done to see if there is a relation of depression to any of the clinical outcomes. It was found that depression had a positive correlation with disease activity score DAS28 (coefficient of correlation 0.167, p = 0.018), VAS pain scores (coefficient = 0.361, p < 0.001) as well as ESR coefficient = 0.217, and p = 0.002. This finding is in agreement with several other studies which report a positive co-relation of depression with disease activity scores, pain and level of inflammatory markers^16,22,23. Pain VAS scores were found to have the most correlation with depression, which supports the pathophysiological hypothesis of interplay between inflammatory pathways and depression. Excessive ROS or insufficient antioxidant defence could contribute to chronic inflammatory pathogenesis of RA, which cause multiple clinical symptoms such as fatigue, morning stiffness and loss of functional ability and even depression.²⁴ This could explain the positive significant correlation between disease activity and depression we saw in our study.

Fatigue in Rheumatoid Arthritis: Fatigue a symptom which is common in RA patients can be measured using the MAF (Multidimensional Assessment of Fatigue). Fatigue severity was measured using MAF. Patients were categorized based on MAF GFI scores 0-10(78%), 10-20(20.5%) and 20-30(1.5%). Further fatigue among the remission and non-remission patient groups was compared using t test and was found to be significant. Thus, we can conclude that fatigue is present to a greater extent in the patients with active disease and improves with improvement in disease activity.

Our study on both depression and fatigue once again emphasises the need for rheumatologists especially in the Indian scenario to address them in their routine clinical practice. This could, for example, take the form of an annual or biennial assessment, delegated to appropriate staff due to paucity of time for rheumatologist himself and should be done on a regular basis just as all other risk factors screening in RA. Techniques like progressive muscle relaxation techniques and guided imagery have already been proven to be beneficial in reducing fatigue and improving quality of life especially among patients with cancer patients undergoing chemotherapy.^25. Such interventions in rheumatoid patients is likely to have similar benefits and needs to be advocated into practice.

Limitation of the study: The study was a cross-sectional, observational design where patient characteristics, clinical parameters were studied in one patient visit. It would have been interesting to study the fluctuations in depression and fatigue score with changes in disease activity which are evident over a period of time. Thus a longitudinal study may be able to give deeper insights rather than a cross-sectional study which can be stated to be a limitation of the study.

CONFLICT OF INTEREST:

The authors have no conflicts of interest regarding this investigation.

ACKNOWLEDGEMENTS:

The authors would like to thank Dr Padmanabhan Shenoy, Rheumatologist and Director, Dr Shenoy’s CARE Hospital, Vytilla, Kochi, Dr Shanoj KC, Ethics Committee and staff for providing the facilities to conduct the study. We would also like to thank the host institutions for their support, and also the patients for their cooperation and patience in completion of the questionnaires.

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Received on 03.11.2021 Modified on 14.03.2022

Research J. Pharm. and Tech 2023; 16(3):1175-1179.

DOI: 10.52711/0974-360X.2023.00195