Article Text
PDF
Abstract
Objective The aim of this study was to explore the effect of depression on pain, disease activity, functional disability and health-related quality of life measured by Visual Analogue Scale, Systemic Lupus Erythematosus Disease Activity Index, Health Assessment Questionnaire and Short Form-36 in patients with systemic lupus erythematosus.
Design Meta-analysis.
Data sources The PubMed, EMBASE, Cochrane Library and Web of Science were searched for obtaining available studies from inception to 7 March 2023.
Eligibility criteria for selecting studies Studies evaluating the impact of depression on pain, disease activity, functional disability and quality of life were included.
Data extraction and synthesis Two authors independently screened publications and extracted data according to set inclusion and exclusion criteria. Statistical analyses were conducted with RevMan V.5.3.0. Data were pooled using a fixed-effects or random-effects model according to heterogeneity.
Results A total of 13 identified studies met the inclusion criteria, reporting on a total of 1911 patients with systemic lupus erythematosus. The Visual Analogue Scale score was significantly higher in patients with depression than those without depression (standardised mean difference (SMD)=0.84 (95% CI 0.27 to 1.42), p=0.004). The Health Assessment Questionnaire score was significantly higher in patients with depression than those without depression (SMD=1.05 (95% CI 0.14 to 1.95), p<0.05). The Systemic Lupus Erythematosus Disease Activity Index score was significantly higher in patients with depression than those without depression (SMD=0.46 (95% CI 0.27 to 0.64), p<0.00001). Scores in most Short Form-36 dimensions (physical function, role physical function, emotional role function, vitality, mental health, social function, general health, physical component scale, mental component scale) were lower in patients with depression than those without depression.
Conclusion This meta-analysis showed that depression was associated with increased in pain, functional disability and disease activity, and decline in health-related quality of life in patients with systemic lupus erythematosus. Awareness of the importance of the relationship between depression in systemic lupus erythematosus patients and pain, functional disability and the quality of life might assist rheumatology physicians and nurses in assessing and preventing these symptoms.
PROSPERO registration number CRD42021265694.
- MENTAL HEALTH
- RHEUMATOLOGY
- Quality of Life
Data availability statement
All data relevant to the study are included in the article or uploaded as supplemental information.
This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
Statistics from Altmetric.com
STRENGTHS AND LIMITATIONS OF THIS STUDY
A greater number of potentially eligible articles were screened and included in the review.
The study selection, data extraction and quality assessment will be performed by two independent investigators. Disagreements, if any, will be resolved by consulting a third investigator.
The study quality and risk of bias will be comprehensively examined by adopting the Newcastle–Ottawa Quality Scale.
The differences in sample size and population sources between studies may be the reason for the heterogeneity.
Due to the limited number of studies, it is impossible to unify the diagnostic methods of depression.
Introduction
As a chronic inflammatory autoimmune disease, systemic lupus erythematosus (SLE) is characterised by loss of self-tolerance, formation of nuclear autoantibodies and immune complexes, and inflammation of multiple organs. The clinical manifestations of SLE are heterogeneous and can involve one or more organs, including lungs, kidneys and central nervous system,1–5 which undoubtedly has a negative impact on the quality of life of patients.
In addition to organic symptoms, mental health problems are also common in patients with SLE.6–16 Nevertheless, mental health problems are often under-recognised and undertreated in patients with SLE. Studies have shown that depression is one of the most common mental illnesses in patients with SLE, and its prevalence ranges from 17% to 75%.17 The reasons why its prevalence is inconsistent may be the heterogeneity of the population, the difference in sample size and the different evaluation tools. Depression in patients with SLE may be related to high-dose prednisone and lymphocyte abnormalities.18 19 What is more, depression affects patients’ perception of their symptoms and physical function, and aggravates fatigue, pain and psychological stress,8 20 which lead to physical disability and decrease quality of life in patients with SLE.14 21 Due to the long course of the disease and its proneness to recurrent episodes, for depression in SLE, early and accurate diagnosis and reasonable treatment should be carried out which have great significance for controlling the progression of the disease and improving the quality of life of patients.
At present, the relationship between depression and treatment outcomes such as pain, disease activity, functional disability and quality of life has not been widely explored. Studies indicated that depression was associated with poor disease activity14; however, another study found that depression had nothing to do with disease activity.20 Therefore, we conducted this meta-analysis to assess the relationship between depression and pain, disease activity, functional disability and quality of life in patients with SLE, so that valuable information for the best management of the disease could be provided.
Methods
We conducted a literature search for studies that assessed the effect of depression on disease activity and health-related quality of life (HRQoL) among patients with SLE. The systematic review and meta-analysis is reported based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement provided by the Cochrane Collaborative.22 23 The selected search strategy and analysis method have been registered in the PROSPERO database (CRD42021265694) and the last search was conducted on 7 March 2023.
Search strategy
The PubMed, EMBASE, Cochrane Library and Web of Science were searched for obtaining available studies from inception to 7 March 2023. In the search, the following keywords and subject words were used: (Depress* OR Depress* disorders OR Dysthymi* OR Mood disorders) AND (Systemic lupus erythematosus OR SLE). See online supplemental appendix 2 for detailed search strategy.
Supplemental material
Inclusion and exclusion criteria
The study inclusion criteria were as follows: (a) studies on patients with SLE diagnosed on the basis of American College of Rheumatology and/or Systemic Lupus International Collaborating Clinic (SLICC) 2012 classification criteria for SLE; (b) studies that enrolled participants aged ≥18 years; (c) studies that use validated methods to evaluate depression, pain, disease activity, functional disability and quality of life; (d) outcome variables must include at least one of the following variables: depression, pain, disease activity, functional disability and quality of life; (e) the type of studies was cross-sectional, cohort or longitudinal; (f) the article was published in English.
Different evaluation tools for the outcome indicators are used. The pain Visual Analogue Scale (VAS) is a self-reported measure of pain intensity which uses a straight line without any division, and marks the pain at both ends of the straight line with scores ranging from 0 (‘no pain’) to 10 (‘worst pain in my life’).24 The disease activity was assessed by SLE Disease Activity Index (SLEDAI), which ranges between 0 and 105: 0, no activity; 1–5, mild activity; 6–10, moderate activity; 11–19, high activity; and ≥20, very high activity.25 Quality of life was evaluated with Short Form-36 (SF-36). It is composed of eight domains, four of which are physical (physical function, role physical function, body pain and general health) and the other four are mental (social function, role emotional function, mental health and vitality) components. The scales physical and mental component summary (PCS, MCS) scores range from 0 (means the worst quality of life) to 100 (means the best quality of life). Impaired SF-36 subscale scores on each SF-36 domain were determined as values lower than the mean values observed for the entire study population.26
The study exclusion criteria were as follows: (a) studies with overlapping or insufficient data; (b) the types of study were review, conference and case reports; (c) the type of study was not cross-sectional design.
Data extraction and study quality assessment
Two independent researchers searched and eliminated duplicate studies. They independently read the title and abstract of the articles so that they could exclude articles that did not meet the inclusion criteria. Then, they read the full text of the remaining studies mentioned above to determine the final article to be included. If it was unclear whether the study met the inclusion criteria, a third investigator was asked for their opinion and an agreement was reached afterwards. The following information was extracted from each study: author, year of publication, country, number of participants, age of participants, disease duration, type of study, assessment tool of depression, diagnostic criteria for SLE and main outcomes.
The quality of each included study was assessed by two independent reviewers through the Newcastle–Ottawa Scale (NOS).27 It evaluates the quality of primary research based on the three areas used in the research: selection, comparability and exposure. NOS is a 9-point scale that identifies the risk of bias associated with the study design. The ‘star system’ is used to judge research from three broad perspectives: (1) selection of study group (0–4 points for case studies, 0–5 points for cross-sectional studies and cohort studies); (2) comparability of groups (0–2 points for case–control, cohort and cross-sectional studies); (3) determining results (0–3 points for case–control, cohort and cross-sectional studies). The NOS is scored separately according to the study design (case–control/cross-sectional study and cohort study). Studies scoring >7 were considered at low risk of bias, scores of 5–7 indicated moderate risk of bias and scores of <5 indicated high risk of bias. If there were any disagreements between the reviewers, the third reviewer was consulted. A consensus was reached through discussion.
Statistical analyses
The meta-analysis used the RevMan software (V.5.3.0) to analyse data. The standardised mean difference (SMD) and 95% CI of the continuous data were calculated to evaluate the change. The heterogeneity between studies was assessed by I2. If I2≥50%, it can be considered that there was heterogeneity between the articles and the random-effects model was used; otherwise, the fixed-effects model was used (I2<50%). The Z test was used to assess for overall effect and p<0.05 was considered statistically significant.
Patient and public involvement
Patients and the public were not involved in this study.
Results
Study selection and characteristics of study
A total of 11 717 articles were identified through our search strategy: 1672 articles in PubMed, 4829 articles in EMBASE, 230 articles in the Cochrane Library and 4986 articles in Web of Science (figure 1). Additionally, six articles were identified by searching the reference lists of selected publications. After removing duplicates, the title and abstract of 7126 articles were screened, and 132 were considered eligible for full-text assessment. After further review of the full text, 119 articles were excluded (32 studies had no appropriate outcomes, 11 studies enrolled participants aged below 18 years, 56 studies did not provide sufficient or useful data, 13 studies were reviews or meta-analyses, 7 studies did not have full text available) and 13 studies were included finally, which involved a total of 1911 participants.14 15 20 21 28–36 The characteristics of the included articles are summarised in the online supplemental table. Four studies were conducted in the America,20 28–30 two in Egypt,21 31 three in China,15 32 36 one in Brazil,14 one in Turkey,34 one in Korea35 and one in Thailand.33 In terms of outcomes, 12 studies assessed disease activity,14 15 20 21 28–33 35 36 5 assessed quality of life,15 28 30 31 34 4 assessed pain by VAS20 28 29 36 and 2 assessed functional disability by Health Assessment Questionnaire (HAQ).14 21 The quality assessment using the NOS is shown in table 1; NOS ranges from 0 to 9 points—one received 8 points,32 four received 7 points,14 18 20 33 six received 6 points29–31 34–36 and two received 5 points,15 21 indicating that most studies have moderate methodological quality.
Supplemental material
Flow chart.
Quality assessment of the included studies measured by NOS
Pain
Four studies20 28 29 36 involving 666 patients reported pain measured by VAS. A random-effects model was used because the heterogeneity test showed an I2 of 90% among the studies. There is a significant difference between patients with and without depression with SLE (SMD=0.84 (95% CI 0.27 to 1.42), p=0.004) (figure 2).
Forest plot of pain in patients with depression versus patients without depression with systemic lupus erythematosus.
Functional disability
Two studies14 21 involving 121 patients reported functional disability measured by HAQ. A random-effects model was used because the heterogeneity test showed an I2 of 78% among the studies. There is a significant difference between patients with and without depression with SLE (SMD=1.05 (95% CI 0.14 to 1.95), p=0.02) (figure 3).
Forest plot of functional disability in patients with depression versus patients without depression with systemic lupus erythematosus.
Disease activity
Twelve studies14 15 20 21 28–33 35 36 involving 1798 patients reported disease activity measured by SLEDAI. A random-effects model was used because the heterogeneity test showed an I2 of 64% among the studies. There is a significant difference between patients with and without depression with SLE (SMD =0.46 (95% CI 0.27 to 0.64), p<0.00001) (figure 4).
Forest plot of disease activity in patients with depression versus patients without depression with systemic lupus erythematosus.
Health-related quality of life
As shown in figure 5, three studies15 31 34 were included in this review for physical function, role physical function, body pain, general health, social function, vitality, role emotional function and mental health dimensions of HRQoL in patients with SLE. They were all significantly lower in most domains, with an overall SMD of −1.08 for physical function (95% CI −1.33 to −0.82), –0.81 for role physical function (95% CI −1.24 to −0.38), –0.52 for body pain (95% CI −1.13 to 0.09), −0.75 for general health (95% CI −0.99 to −0.50), –3.31 for PCS (95% CI −5.79 to −0.83), –1.09 for social function (95% CI −1.54 to −0.63), –1.12 for vitality (95% CI −1.37 to −0.87), –1.25 for role emotional function (95% CI −2.06 to −0.44), –0.94 for mental health (95% CI −1.43 to −0.46) and −4.98 for MCS (95% CI −7.79 to −2.17). Due to the heterogeneity between various aspects, the random-effects model is used to estimate the overall effect, instead of the fixed-effects model.
Forest plot of health-related quality of life in patients with depression versus patients without depression with systemic lupus erythematosus. (A) Four domains of PCS (PF, RP, BP and GH) and PCS. (B) Four domains of MCS (SF, VT, RE and MH) and MCS. BP, body pain; GH, general health; MCS, mental component summary; MH, mental health; PCS, physical component summary; PF, physical function; RE, role emotional function; RP, role physical function; SF, social function; VT, vitality.
Discussion
This is the first meta-analysis to explore the relationship between depression and pain, disease activity, functional disability and HRQoL in patients with SLE. Findings suggest that depression is associated with increased pain, disease activity and functional disability, and reduced quality of life.
The quality of the 13 types of research included in this study is medium, of which 11 display a quality score of ≥6 points, and only 2 researches display 5 points. The inclusion and exclusion criteria of the subjects were clearly stated in the original research, and the diagnostic methods of depression were clearly pointed out in 13 articles. The main outcome indicators and evaluation methods were relatively consistent among the studies, and the heterogeneity was relatively low. Therefore, the quality of the original research included in this study is acceptable. The final meta-analysis results of the outcome indicators are of high reliability and stability, but the methodological quality of some of the original research included is low, which may affect the reliability of the final results.
This systematic review demonstrates that depression is associated with increased pain, which is in line with previous studies.20 29 The link between pain and mood disorders in rheumatism has long been established. The latest understanding of this interface shows the contribution of biological and psychological factors. The relationship between pain and depression is complex and is likely to be two way. The presence of pain can cause many depressive symptoms, including lack of happiness, poor sleep quality, fatigue, etc.37 ,38Furthermore, research had indicated that in terms of treatment, for arthritis patients with depression, improvements could be made not only in emotional well-being but also in reducing pain, enhancing functional status, and increasing quality of life.
In previous studies, the relationship between disease activity and depression is not quite clear. Some scholars believe that depression is related to increased disease activity,14 15 21 while some studies have shown that depression has nothing to do with disease activity.20 The results of this study show that depression is associated with higher disease activity. The reason for such a result is that increased disease activity may lead to pain and depression, which in turn increases fatigue. What is more, studies have shown that the SLEDAI scores were a strong predictor of depression in patients with SLE.15
It was found in this study that patients with depression with SLE have poorer SF-36 scores than those without depression with SLE, particularly in physical function, limited emotions, energy, fatigue and emotional well-being, all of which have an impact on quality of life. Dietz et al have the same discovery and documented that depression is associated with low HRQoL.30A strategy was proposed for coping with this disease: expressing it with daily tasks and hoping for a better life. Therefore, in daily clinical practice, the high quality of life of patients with SLE is related to depression and fatigue to varying degrees.
There are several limitations in the current meta-analysis. This meta-analysis is limited by a small number of studies that provide appropriate data to allow statistics to aggregate the results. When a summary estimate of correlation is obtained, and there is heterogeneity, it should be interpreted with caution. The potential sources of heterogeneity are differences in source populations, sampling methods and adjustments to confounding factors between different studies. The heterogeneity may reduce the generalisation of results. Therefore, a random-effects model is used. Thus, high-quality and more rigorously designed research with a large sample size will be needed in the future.
Data availability statement
All data relevant to the study are included in the article or uploaded as supplemental information.
Ethics statements
Patient consent for publication
Ethics approval
Not applicable.
Acknowledgments
We would like to thank Xiaoyu Chen and Teng Zhang for their assistance with this study.
References
Supplementary materials
Supplementary Data
This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.
Footnotes
QZ, XL and HC are joint first authors.
QZ, XL and HC contributed equally.
JM and BS contributed equally.
Contributors QZ, XL and HC—data curation, formal analysis, methodology, writing (original draft) and writing (review and editing). LW—conceptualisation, formal analysis and writing (review and editing). NW—conceptualisation and writing (review and editing). JM and BS—resources, writing (review and editing), supervision and funding acquisition. BS is responsible for the overall content as the guarantor.
Funding This work was supported by the Jiangsu Provincial Commission of Health and Family Planning Foundation (grant number Z201622); Jiangsu Province ‘333 high-level talent training project’ Foundation (grant number BRA2016198); Jiangsu Province Youth Medical Talent Foundation (grant number QNRC2016409); Jiangsu Province six talent peak high-level personnel training project Foundation (grant number WSN-234); and Nantong Science and Technology Plan Project (grant number MS12019007).
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review Not commissioned; externally peer reviewed.
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.