A STUDY ON ASSESSMENT OF DEPRESSION AND SLEEP DISTURBANCES AMONG PATIENTS WITH RHEUMATOID ARTHRITIS

A STUDY ON ASSESSMENT OF DEPRESSION AND SLEEP DISTURBANCES AMONG PATIENTS WITH RHEUMATOID ARTHRITIS

Nanda Gopala Krishna Gona *, Sony Priyanka Arava, Bhargavi Pacchipala, Alekhya Somepalli and Chanukya Senapathi

Department of Pharmaceutical Analysis, A. S. N. Pharmacy College, Burripalem Road, Tenali, Andhra Pradesh, India.

ABSTRACT: The prevalence of Rheumatoid Arthritis is 0.1% to 1% and it is most common in developed countries. More than 2/3^rd [54%-70%] of patients with RA have sleep disturbances. In RA multiple episodes of inflammation are predictive of an increased risk of developing depression. The prevalence of depression in individual RA ranges 14% to 48%. Sleep disturbances & depression in those with RA patients worsen their quality of life and impair their daily activity. Sleep issues and depressions have the potential to disrupt the effectiveness of treatments for RA. By addressing their concerns, we can enhance treatment compliance. There is a bidirectional relationship between RA, sleep disturbance & depression, poor sleep and depression can worsen RA symptoms. Understanding this complex scenario is crucial for the comprehensive care. Identifying and addressing sleep problems & depression can lead to better management strategies. These may involve lifestyle changes medication adjustments or mental health interventions to improve both physical & emotional well-being. This study is essential for enhancing their wellbeing, optimizing treatment outcomes and providing comprehensive care.

Keywords: Rheumatoid arthritis, Depression, Patients, Sleep disturbances, Inflammation

INTRODUCTION: Rheumatoid Arthritis (RA) constitutes a chronic, autoimmune and systemic inflammatory disorder. It is known to have a wide range of effects beyond the joints, with established impact on sleep and mood ¹. There is a higher prevalence of depression amongst arthritis patient ². It is characterized by inflammation of the joints, leading to pain, stiffness and swelling. It not only affects physical functioning but also has a profound impact on mental health ³.

Sleep problems occur in 54–70% of RA patients and include poor quality, difficulty falling asleep, non-restorative sleep, awakening during the night, wakefulness and excessive daytime sleepiness ⁴. In RA patients, sleep problems may be caused by pain ⁵, mood, and disease activity ⁶. Sleep quality has been affected indirectly by pain through disease activity.

Moreover, by triggering a depressive mood, pain can contribute to sleep disturbance as well ⁷. Depressive symptoms in RA have been associated with increased pain ⁸, physical disability ⁹, co morbidities ¹⁰, reduced quality of life ¹¹ and higher mortality levels ¹². Recently, it has been reported that baseline and persistent depressive symptoms are associated with worse response to treatment and poorer long-term health outcomes ¹³.

Effects of Rheumatoid Arthritis on Sleep Disturbances: Poor sleep quality has been linked to pain, mood, fatigability, stress and disease activity in the rheumatoid disease population.

Pain and Discomfort: The inflammation in the joints can lead to persistent pain, making it difficult for RA patients to find a comfortable sleeping position. This pain can keep them awake at night, leading to difficulties falling asleep and frequent awakenings.

Stiffness and Joint Discomfort: Stiffness in the joints especially in the morning can cause significant discomfort making it challenging for patients to get out of bed or change their positions during sleep.

Fatigue: RA patients often experience fatigue, which can be both physical and mental. This fatigue can cause excessive daytime sleepiness and a constant feeling of tiredness, affecting the quality of sleep at night.

Medication Side Effects: Some medications used to manage RA symptoms such as corticosteroids, can interfere with normal sleep patterns and contribute to insomnia or restless sleep for RA patients.

Sleep Apnea: Sleep Apnea, a disorder characterized by interrupted breathing during sleep, can further disrupt the quality of sleep and contribute to daytime sleepiness. There is a higher prevalence of sleep Apnea in RA patients compared to the general population ¹⁸.

Effects of Rheumatoid Arthritis on Depression:

Chronic Pain: Persistent pain experienced by RA patients can not only impact sleep but also contribute to the development or worsening of depression. The constant discomfort and limitations in activities can result in feelings of sadness, helplessness and loss of interest in previously enjoyed activities.

Functional impairment: The physical limitations caused by RA may restrict a person’s ability to engage in social activities, work or hobbies. These limitations can lead to feelings of isolation, dependency, frustration and increasing the risk of depression.

Inflammatory Processes: Inflammation a hallmark of RA can also affect the brain. Chronic inflammation may disturb the balance of neurotransmitters such as serotonin, which play a crucial role in mood regulation, potentially contributing to depressive symptoms.

Psychosocial Factors: The impact of living with a chronic disease like RA can affect a person’s self-esteem, body image, relationships and financial burdens. The uncertainty of disease progression and the need for ongoing medical care can all contribute to increased stress levels and the development of depression ¹⁹.

It is important for healthcare providers to address both sleep problems and depression in RA patients, as they can significantly impact a patient’s overall well-being and quality of life ²⁰. Treatment options include management of pain and inflammation, lifestyle modifications, cognitive behavioural therapy, medications for sleep or depression and when necessary, referral to mental health professionals for further evaluation and support ²¹.

Laboratory Tests:

Erythrocyte Sedimentation Test: The erythrocyte sedimentation rate (ESR) test was employed to assess the extent of inflammation in the body by measuring the rate at which red blood cells separated from other blood cells when treated with an anti-clotting substance in a laboratory setting. Clumping of red blood cells, indicative of inflammation resulted in faster separation. Elevated ESR levels suggested heightened inflammation while low levels indicated minimal inflammation. Although the ESR test alone was insufficient for diagnosing rheumatoid arthritis, it served as a valuable indicator. Various chronic conditions, infections or injuries could trigger inflammation and increased ESR levels guiding doctors in identifying potential causes. For instance, markedly elevated ESR levels would likely signify an infection rather than rheumatoid arthritis ³⁰.

C– Reactive Protein Test: The C-reactive protein test was commonly utilized for assessing inflammation which played a crucial role in diagnosing rheumatoid arthritis and monitoring disease activity as well as response to treatments. Various other blood tests encompassing assessments of kidney function, electrolytes, liver function, thyroid function, muscle markers, autoimmune markers and infection markers were conducted to evaluate overall health and consider alternative diagnoses.

Additionally, specific tests tailored for rheumatoid arthritis were occasionally considered. In the investigation of potential joint damage, imaging tests were employed to provide insights into the condition and progression of disease ³¹.

Rheumatoid Factor Test (RF): This blood test checks for Rheumatoid Factor, an antibody that many people with rheumatoid arthritis can eventually have in their blood. An antibody is a special protein made by the immune system that normally helps fight invaders in the body ³².

Anti–Cyclic Citrullinated Peptide Antibody Test: This blood test checks for anti-CCP antibodies which appear in many people with rheumatoid arthritis. In addition, anti-CCP can appear before RA symptoms develop, which can help to diagnose the disease early. This test’s results, along with the results from RF blood tests, are useful for confirming rheumatoid arthritis diagnosis ³³.

Complete Blood Count Test: This blood test measures different blood cell counts and can help diagnose anemia which is common in people with RA ³⁴.

Other Tests: There’s no cure for rheumatoid arthritis, but treatment can help manage your symptoms. However, multiple blood tests can indicate rheumatoid arthritis is the likely cause of your symptoms. In addition to blood tests, various diagnostic methods are employed to confirm rheumatoid arthritis ³⁵. These include:

Physical Assessment: Evaluating the impact of symptoms on daily life involves assessing the ability to perform tasks like showering, eating, and dressing. A physical therapist may also examine grip strength, walking patterns, and balance ³⁶.

Joint Scan: This diagnostic method aims to identify inflammation and damage in joints, providing valuable information to support the confirmation of a rheumatoid arthritis diagnosis ³⁷.

Imaging Tests: X-rays and MRIs generate detailed images of bones, muscles, and joints, aiding in the diagnosis of rheumatoid arthritis by revealing structural changes and abnormalities ³⁸.

Research Methodology: This was a cross-sectional observational study conducted for a period of 6months with sample size of 189 study participants at Health Hospital, Tenali, Guntur district. The data was collected using Pittsburgh Sleep Quality Index. This measures the sleep quality reported during the previous 4 weeks. It has 19 items that measure the 7 components of sleep which include sleep quality, sleep latency, sleep duration, sleep efficiency, sleep disturbances, use of sleep medication and daytime dysfunction. APSQI score ≥ 5 (max score 21) determines poor quality of sleep. Depression was assessed by Patient Health Questionnaire (PHQ-9), a 9-item questionnaire with each question scoring 0-3, PHQ score ranges from 0-27 with higher scores indicating lower mood. A total score of 5 considered to be a positive result for depression. Disease activity of RA was measured by using Disease Activity Score (DAS-28). It includes assessment of Tender Joint Count (TJC), Swollen Joint Count (SJC), Erythrocyte Sedimentation Rate (ESR) or C-reactive protein (CRP) and the activity classified as remission (<2.6), low (2.6-<3.2), moderate (>3.2-<5.1) or high (>5.1).

Study Criteria:

Inclusion Criteria: Both the genders of male and female patients above the age of 18 years, Patients diagnosed with RA, Individuals willing to participate and who provide informed consent are included in the study.

Exclusion Criteria: Patients with severe medical or psychiatric conditions and co-morbid conditions will be excluded and Patients with previous medication history or medical history of sleep or mood disorders unrelated to RA will be excluded, Pediatrics, pregnant women and patients not willing to participate will be excluded.

RESULTS: Table 1 represents the gender wise categorization of study participants. A total of 189 study participants were recruited in this study. Among them, 49(25.9%) were found to be males and 140(74.1%) were found to be females.

TABLE 1: GENDER WISE CATEGORIZATION OF THE STUDY PARTICIPANTS

FIG. 1: GENDER DISTRIBUTION

Table 2 represents the age wise categorization of the study participants. Among the 189 study participants, 1(0.5%) was below 30 years of age, 19(10.1%) were of 31-40 years age group, 84(44.5%) were of 41-50 years age group, 61(32.3%) were of 51-60 years age group, 22(11.6%) were of 61-70 years age group and 2(1.0%) were of 71-80 years of age.

TABLE 2: AGE WISE CATEGORIZATION OF STUDY PARTICIPANTS

FIG. 2: AGE WISE DISTRIBUTION

Table 3 represents the categorization of study participants based on occupation. Among 189 study participants, 43(87.8%) males and 34(24.2%) females were employed. About 6(12.2%) males and 106 (75.8%) females were unemployed.

TABLE 3: CATEGORIZATION OF STUDY PARTICIPANTS BASED ON OCCUPATION

FIG. 3: OCCUPATIONAL DISTRIBUTION

Table 4 represents the categorization of study participants based on personal history of smoking status. Among 189 subjects, 26(53.1%) males and 3(2.1%) females were smokers. About 23(46.9%) males and 137 (97.9%) females were non-smokers.

TABLE 4: CATEGORIZATION OF STUDY PARTICIPANTS BASED ON SMOKING STATUS

FIG. 4: SMOKING STATUS

Table 5 represents the categorization of study participants based on personal history of alcohol intake. Among 189 subjects, 24(48.9%) males and 3(2.1%) females were alcoholic. About 25(51.1%) males and 137 (97.9%) females were non alcoholic.

TABLE 5: CATEGORIZATION OF STUDY PARTICIPANTS BASED ON ALCOHOLIC STATUS

FIG. 5: ALCOHOLIC STATUS DISTRIBUTION

Table 6 represents the categorization of study participants based on this verity of depression.

In this study 189 subjects were included. Among them 28(14.9%) were observed with no depression between the score of 1-4, 102(53.9%) were observed with mild depression between the score of 5-9, 49(25.9%) were observed with moderate depression between the score of 10-14, 1 (0.5%) was observed with moderately severe depression between the score of 15-19 and 9 (4.8%) were observed with severe depression between the score of 20-27 based on patient health questionnaire interpretation (PHQ-9).

TABLE 6: CATEGORIZATION OF STUDY PARTICIPANTS BASED ON SEVERITY OF DEPRESSION

FIG. 6: SEVERITY OF DEPRESSION

Table 7 represents the categorization of study participants based on depression status. Among 189 study participants, 41(83.7%) males and 120(85.8%) females were observed with depression. About 8(16.3%) males and 20(14.2%) females were not observed with depression.

TABLE 7: CATEGORIZATION OF STUDY PARTICIPANTS BASED ON DEPRESSION STATUS

FIG. 7: DEPRESSION STATUS

Table 8 represents the categorization of study participants based on difficulties faced during depression in performing work, managing house hold task and interacting with others. Among 189 study participants, 120(63.5%) were observed with no difficulty, 61(32.3%) were observed with somewhat difficulty, 8(4.2%) were observed with very difficult and no one were observed with extremely difficulty.

TABLE 8: CATEGORIZATION OF STUDY PARTICIPANTS BASED ON DIFFICULTIES FACED DURING DEPRESSION

FIG. 8:  DIFFICULTIES DURING DEPRESSION

Table 9 represents the categorization of study participants based on activity of the disease. Among 189 study participants, 1 (0.5%) was observed with remission between the score of 0-2.6, 4(2.1%) were observed with low disease activity between the score of 2.6-3.2, 93(49.2%) were observed with moderate disease activity between the score of 3.2-5.1 and 91 (48.2%) were observed with the score greater than 5.1 which indicates high disease activity based on Disease Activity Score 28.

TABLE 9: CATEGORIZATION OF STUDY PARTICIPANTS BASED ON DISEASE ACTIVITY

FIG. 9:  DISEASE SEVERITY

Table 10 represents the categorization of the study participants according to their sleep quality. Among 189 subjects with rheumatoid arthritis, 7 (3.7%) were experienced with very good quality of sleep, 97(51.4%) were experienced with fairly good sleep quality, 70(37.0%) were experienced with fairly bad sleep quality and 15 (7.9%) were experienced with very bad sleep quality.

TABLE 10: CATEGORIZATION OF STUDY PARTICIPANTS BASED ON SLEEP QUALITY

FIG. 10: SLEEP QUALITY

Table 11 represents the categorization of study participants based on sleep latency. Among 189 subjects with rheumatoid arthritis, 23 (12.1%) fall asleep during night within less than 15minutes, 54(28.5%) subjects usually take 16-30 minutes to fall asleep, 41(21.6%) subjects usually take 31-60 minutes to fall asleep and 71 (37.8%) subjects usually take greater than 60 minutes to fall asleep during night.

TABLE 11: CATEGORIZATION OF STUDY PARTICIPANTS BASED ON SLEEP LATENCY

FIG. 11: SLEEP LATENCY

Table 12 represents the categorization of the study participants based on their sleep duration. Among 189 subjects with rheumatoid arthritis, 67 (35.5%) were observed with greater than 7 hours of sleep daily, 69 (36.5%) were observed with 6-7 hours of sleep, 32 (16.9%) were observed with 5-6 hours of sleep and 21(11.1%) were observed with less than 5 hours of sleep.

TABLE 12: CATEGORIZATION OF STUDY PARTICIPANTS BASED ON SLEEP DURATION

FIG. 12: SLEEP DURATION

Table 13 represents the categorization of the study participants based on sleep efficacy. Among 189 subjects with rheumatoid arthritis, 132 (69.9%) were observed with greater than 85% of sleep efficacy, 28 (14.8%) were observed with 75-84 % of sleep efficacy, 18 (9.5%) were observed with 65-74 % of sleep efficacy and 11 (5.8%) were observed with less than 65 % of sleep efficacy.

TABLE 13: CATEGORIZATION OF STUDY PARTICIPANTS BASED ON SLEEP EFFICIENCY

FIG. 13: SLEEP EFFICACY

Table 14 represents the categorization of the study participants based on their sleep disturbances. Among 189 subjects with rheumatoid arthritis, 10(0.5%) were not observed with sleep disturbances during the past month, 136 (72.0%) were observed with sleep disturbances less than once a week, 51 (27.0%) were observed with sleep disturbances in once or twice a week and 1(0.5%) was observed with sleep disturbances in three or more times a week.

TABLE 14: CATEGORIZATION OF STUDY PARTICIPANTS BASED ON SLEEP DISTURBANCES

FIG. 14: SLEEP DISTURBANCES

Table 15 represents the categorization of the study participants based on the use of sleep medication. Among 189 subjects with rheumatoid arthritis, 144(76.2%) had not used medication for sleep during the past month, 11(5.8%) were used medication for sleep less than once a week, 12(6.4%) were used medication for  sleep in once or twice a  week and   22(11.6%) were used medication for sleep in three or more times a week.

TABLE 15: CATEGORIZATION OF STUDY PARTICIPANTS BASED ON USE OF SLEEP MEDICATION

FIG. 15: USE OF SLEEP MEDICATION

Table 16 represents the categorization of the study participants based on their daytime dysfunction. Among 189 subjects with rheumatoid arthritis, 12 (6.3%) subjects were not observed with daytime dysfunction, 129 (68.3%) subjects were observed with dysfunction and had a very slight problem, 41(21.7%) subjects were observed with dysfunction caused somewhat a problem in doing things and 7 (3.7%) subjects were observed with dysfunction and had a very big problem.

TABLE 16: CATEGORIZATION OF STUDY PARTICIPANTS BASED ON DAY TIME DYSFUNCTION

FIG. 16: OVERALL SLEEP QUALITY

Table 17 represents the categorization of the study participants based on their overall quality of sleep. Among 189 subjects with rheumatoid arthritis, 32 (16.9%) were observed with good sleep quality, 99(52.4%) were observed with poor sleep quality and 58(30.7%) were observed with worst sleep quality.

TABLE 17: CATEGORIZATION OF STUDY PARTICIPANTS BASED ON OVERALL SLEEP QUALITY

FIG. 17: DAYTIME DYSFUNCTION

DISCUSSION: A total of 189 study participants were recruited in the study. Among them 49 (25.9 %) were found to be males and 140 (74%) were found to be females. Most of the study participants were observed in the age group of 41-50 years (44.5%) followed by the age group of 51-60years (32.3%). The majority of the study participants were non-smokers (84.7%) and non-alcoholic (85.7%). In the aspect of severity of depression most of the patients were mild (53.9%) followed by moderate (25.9%). In this study the disease activity score was interpret ant by means of DAS 28 assessment. Almost half of the study participants were observed with moderate disease activity (49.2%) followed by high disease activity (48.2%). The overall mean disease activity score of the study participants was observed to be 5.127 (±1.04). In the aspect of sleep quality half of the study participants were observed with fairly good sleep (51.4%) followed by fairly bad (37%) and very bad (7.9%). The overall mean score of the component 1 (sleep quality) was observed to be 1.49 (±0.69). In the aspect of sleep latency most of the study participants were observed with a sleep latency of >60 minutes (37.8%). The overall mean score of the component 2 (sleep latency) was observed to be 1.84 (±1.06). In the aspect of sleep duration most of the study participants were observed with sleep duration of 6 to 7 hours (36.5%). The overall mean score of the component 3 (sleep duration) was observed to be 1.03 (± 0.98). In the aspect of sleep efficiency most of the study participants were observed with sleep efficiency of greater than 85% (69.9%). The overall mean score of the component 4 (sleep efficiency) was observed to be 0.513(±0.89). In the aspect of sleep disturbances most of the study participants were observed with sleep disturbances, less than once a week (72%). The overall mean score of the component 5 (sleep disturbances) was observed to be 1.27 (±0.47). In this study, the overall mean score of Pittsburgh sleep quality index was observed to be7.89 (±3.33).

CONCLUSION: In this study, the prevalence of depression among the patients with rheumatoid arthritis was found to be (85.1%). The severity of depression was observed to be mild followed by moderate in the majority of the study participants. Among the patients with rheumatoid arthritis patients were observed with moderate disease activity followed by high disease activity.

In conclusion, the prevalence of depression was observed to be very high among patients with rheumatoid arthritis. Clinical pharmacists should take the responsibility along with rheumatologist in association with psychiatrist in the aspect of the management of rheumatoid arthritis associated with psychiatric disorders like depression that helps in providing a better patient care and with an increased health related quality of life among them.

ACKNOWLEDGEMENT: The author's would like to thank Health Hospitals, Tenali, Guntur District for providing necessary facilities to carry out the study.

CONFLICTS OF INTEREST: The author declares that no conflict of interest exists.

REFERENCES:

1. Mark Hughes, Alan Chalk, Poonam Sharma, Sandeep Dahiya and James Galloway: Across-sectional study of sleep and depression in a rheumatoid arthritis population 2021; 1299-1305.
2. Catalina-Elena Ionescu, Claudiu costinel Popescu, Mihaela Agache and Georgiana Dinacheand Catalin Codreanu: Depression in Rheumatoid Arthritis: A Narrative Review-Diagnostic Challenges, Pathogenic Mechanisms and Effects 2022; 1637.
3. Isela Esther Juárez-Rojop, Ana Fresan, Alma Delia Genis-Mendoza 34, Carolina Cerino-Palomino, German Alberto Nolasco-Rosales, Thelma Beatriz González-Castro, Maria Lilia López-Narváez, Francisco Olan, Mario Villar-Soto, Carlos Alfonso Tovilla-Zárate and Humberto Nicolini: Prevalence of poor sleep quality and associated factors in individuals with rheumatoid arthritis: a cross sectional study 2023; 1633.
4. Abdullah Radwan and Ahmed Borai: Quality of sleep-in rheumatoid arthritis patients:  Relationship with disease activity. Depression and Functional Status 2021; 183-187.
5. Susanne Brandstetter, Gertraud Riedelbeck, Mark Steinmann, Boris Ehrenstein, JulikaLoss and Christian Apfelbacher: Pain, social support and depressive symptoms in patients with rheumatoid arthritis. Testing the Stress-Buffering Hypothesis 2017; 931-936.
6. Abad VC, Sarinas PS and Guilleminault C: Sleep and rheumatologic disorders 2008; 211-228.
7. Kontodimopoulos N, Stamatopoulou E, Kletsas G and Kandili A: Disease activity and sleep quality in rheumatoid arthritis. A Deeper Look into the Relationship 2019; 1-8.
8. Fernando Henrique Azevedo Lopes, Max Victor Carioca Freitas, Veralice Meireles Salesde Bruin & Pedro Felipe Carvalhedo deBruin 2021.
9. Yasser M El-Miedany and Amany Haroun El Rasheed: is anxiety a more common disorder than depression in Rheumatoid arthritis 2002; 300-306.
10. Katz PP and Yelin EH: Prevalence and correlates of depressive symptoms among persons with rheumatoid arthritis 1993; 790-796.
11. Mikuls T, Saag K, Criswell L, Merlino L and Cerhan JR: Health related quality of life in women with elderly onset rheumatoid arthritis 2003; 952–957.
12. Ang D, Choi H, Kroenke K and Wolfe F: Comorbid depression is an independent risk factor for mortality in patients with rheumatoid arthritis 2005; 1013–1019.
13. Matcham F, Norton S, Scott DL, Steer S and Hotopf M: Symptoms of depression and anxiety predict treatment response and long-term physical health outcomes in rheumatoid arthritis: secondary analysis of a randomized controlled trial 2016; 268–278.
14. W.tański, N. świątoniowska-lonc, A. tomasiewicz K, dudek B and jankowska-polańska: The impact of sleep disorders on the daily activity and quality of life in rheumatoid arthritis patients – a systematic review and meta-analysis 2022; 3212-3229.
15. Vgontzas AN, ZoumakisE, Bixler EO, LinHM, FollettH, Kales A, Chrousos GP; Adverse effects of modest sleep restriction on sleepiness, performance, and inflammatory cytokines 2004; 2119-2126.
16. Karatas G, Bal A, Yuceege M, Yalcin E, First H, Dulgeroglu D, Karataş F, Sahin S, Cakci A and Ardic S: The evaluation of sleep quality and response to anti-tumor necrosis factor α therapy in rheumatoid arthritis patients 2017; 45-50.
17. Ng KJ, Huang KY, Tung CH, Hsu BB, Wu CH, Lu MC and Lai NS: Risk factors, including different biologics, associated with depression and anxiety in patients with rheumatoid arthritis: across-sectional observational study 2020; 737-746.
18. Cheng-Zhen Jia Cheng-Zhen Jia, Meng-Yao Zhang Meng-Yao Zhang, Bo-Han Li Bo-Han Li, Meng WeiMeng Wei and Guo-Cui Wu: Association Between Sleep Traits and Rheumatoid Arthritis: A Mendelian Randomization Study 2022.
19. Olofsson T, Nordin A, Bergman S, Sonesson S, Broman J-E and Hessel strand R: Fatigue in Patients with Rheumatoid Arthritis - Association with Sleep Disturbance, Reproduction of Pain and Objective Inflammatory Markers 2014; 121.
20. Wesam Gouda, Mona Mokhtar, Seham A. Elazab, Reem Alreefi, Taif Alomar, Fatimah Kushk, Raghad Alahmadi and Mayada Khaliland Mohamed Kamal: Sleep disorders in patients with rheumatoid arthritis: association with quality of life, fatigue, depression levels, functional disability, disease duration, and activity: a multicenter cross-sectional study 2023.
21. Jacqueline Bullock,  Syed A.A. Rizvi, Ayman M. Saleh, Sultan S. Ahmed, Duc P.Do, Rais A. Ansari and Jasmin Ahmedf: Rheumatoid Arthritis: A Brief Overview of the Treatment 2019; 501–507.
22. Vasco C. Romão and Joao Eurico Fonseca: Etiology and Risk Factors for Rheumatoid Arthritis: A State of the Art Review 2021.
23. Vivianne Malmstrom, Christina Trollmo and Lars Klareskog: The Additive Role of Innate and Adaptive Immunity in the Development of Arthritis 2004; 196-201.
24. Yoshika Tanaka: Rheumatoid Arthritis 2020 40-20.
25. Josef S. Smolen, Daniel Aletaha, Kazuhiko Yamamoto; Rheumatoid Arthritis 2018.
26. McInnes IB and Schett: Pathogenetic insights from the treatment of rheumatoid arthritis 2017; 2328-2337.
27. Yoshiya Tanaka and Takeshi Ohira: Mechanisms and therapeutic targets for bone damage in rheumatoid arthritis 2018; 110-119.
28. Tanaka Y and J Bone Miner Metab: Clinical immunity in bone and joint 2019; 2–8.
29. Srakocic S: Blood Tests Used to Diagnose Rheumatoid Arthritis 2021.
30. Janet E. Pope and Ernest H. Choy: C-reactive protein and implications in rheumatoid arthritis and associated co-morbidities 2021; 219-229.
31. Gioud-Paquet M, Auvinet M, Raffin T, Girard P, Bouvier M, Lejeune E, Monier JC; IgM rheumatoid factor (RF), IgA RF, IgE RF and IgG RF detected by ELISA in rheumatoid arthritis 1987; 65-71.
32. M. A. Quinn, A. K. S. Gough, M. J. Green, J. Devlin, E. M. A. Hensor, A. Greenstein, A. Fraser and P. Emery: Anti-CCP antibodies measured at disease onset help identify seronegative rheumatoid arthritis and predict radiological and functional outcome 2006; 478–480.
33. Lana Bandoim; Rheumatoid Arthritis: Tests to Diagnose and Monitor RA Several blood and imaging tests are needed to confirm RA 2023.
34. Jenna Fletcher: How do doctors diagnose arthritis 2023.
35. Yimy F Medina, Alvaro J Ruiz and Martin A Rondon: A Standardized Physical Examination Method for Joints to Determine Rheumatoid Arthritis Activity Using the Modified RAND/UCLA Appropriateness Method 2023; 1287–1299
36. Daniel J. Wallace, Michael Brachman, James R.K linenberg: Joint scanning in rheumatoid arthritis: A literature review 1981; 172-176.
37. Ladislav Šenolt, Walter Grassi and Peter Szodoray: Laboratory biomarkers or imaging in the diagnostics of rheumatoid arthritis 2014.
38. Isela Esther Juárez-Rojop, Ana Fresán, Alma Delia Genis-Mendoza, Carolina Cerino-Palomino, German Alberto Nolasco-Rosales, The lma Beatriz González-Castro, María Lilia López-Narváez , Francisco Olan , Mario Villar-Soto, Carlos Alfonso Tovilla-Zárate and Humberto Nicolini: Prevalence of Poor Sleep Quality and Associated Factors in Individuals with Rheumatoid Arthritis: A Cross-Sectional Study.
39. Mark Hughes, Alan Chalk, Poonam Sharma, Sandeep Dahiya and James Galloway: Across-sectional study of sleep and depression in a rheumatoid arthritis population 2021; 1299–1305.
40. René Westhovens, Kristien Van der Elst, Ann Matthys, Michelle Tran, Isabelle Gilloteau; Sleep problems in patients with rheumatoid arthritis 2014; 31-40.
41. Ana Claudia Janiszewski Goes, Larissa Aparecida Busatto Reis, Marilia Barreto G Silva, Barbara Stadler Kahlow and Thelma L Skare: Rheumatoid arthritis and sleep quality; 2017; 294-298.
42. Perry M Nicassio, Sarah R Ormseth, Morgan Kay, Mara   Custodio, Michael RIrwin, Richard Olmstead and Michael HWeisman: The contribution of pain and depression to self-reported sleep disturbance in patients with rheumatoid arthritis 2012; 107-112.
43. M. A. Quinn, A. K. S. Gough, M. J. Green, J. Devlin, E. M. A. Hensor, A. Greenstein, A. Fraser and P. Emery: Anti-CCP antibodies measured at disease onset help identify seronegative rheumatoid arthritis and predict radiological and functional outcome 2006; 478–480.
    

    ---

    How to cite this article:

    Gona NGK, Arava SP, Pacchipala B, Somepalli A and Senapathi C: A study on assessment of depression and sleep disturbances among patients with Rheumatoid arthritis. Int J Pharm Sci & Res 2024; 15(11): 3359-70. doi: 10.13040/IJPSR.0975-8232.15(11).3359-70.

    ---

    All © 2024 are reserved by International Journal of Pharmaceutical Sciences and Research. This Journal licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License.