Research Review By Dr. Jeff Muir©


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Date Posted:

March 2022

Study Title:

Association Between Depressive Symptoms or Depression and Health Outcomes for Low Back Pain: A Systematic Review and Meta-analysis


Wong JJ, Tricco AC, Côté P, Liang CY, Lewis JA, Bouck Z & Rosella LC

Author's Affiliations:

Epidemiology Division, Dalla Lana School of Public Health, University of Toronto, Canada; Centre for Disability Prevention and Rehabilitation, Ontario Tech University and Canadian Memorial Chiropractic College, Oshawa, Canada; Li Ka Shing Knowledge Institute of St. Michael’s Hospital, Unity Health Toronto, Canada; Institute of Health Policy, Management and Evaluation, University of Toronto; Faculty of Health Sciences, Ontario Tech University; Centre for Drug Policy and Evaluation, Li Ka Shing Knowledge Institute of St. Michael’s Hospital, Unity Health Toronto; ICES, Toronto, Ontario, Canada; Stephen Family Chair in Community Health, Institute for Better Health, Trillium Health Partners, Mississauga, Canada

Publication Information:

Journal of General Internal Medicine 2021 Aug 12. doi: 10.1007/s11606-021-07079-8. Epub ahead of print. PMID: 34383230.

Background Information:

Low back pain (LBP) had a worldwide prevalence of 7.8% in 2017 (1) and remains a leading cause of both disability (2-4) and driver of high healthcare utilization and costs (5). Depression is likewise a leading cause of disability and is a common comorbidity in individuals with LBP, which may further negatively impact outcomes (6-11).

Systematic reviews have attempted to evaluate the role of depressive symptoms as prognostic factors for LBP, but these studies have generally yielded inconsistent results (12, 13). Previous studies have reported weak or no associations with work-related outcomes (12, 13), while others have found inconsistent results due to poor methodological quality (14) or differing study designs (15, 16). Additionally, these reviews are somewhat out of date and require updating for new eligible studies.

Prognostic factors regarding the role of depressive symptoms in LBP are critically important to both future research and patient care, but are also important at a healthcare system level, as identifying prognostic factors can inform healthcare planning and allocation of resources. To address these needs, the authors conducted a systematic review to evaluate the association between depressive symptoms and health outcomes in patients with LBP.

Pertinent Results:

Eligible Studies:
62 studies were eligible for inclusion, of which 14 were included in the meta-analysis (total sample size: 18 843 participants). The results of 48 studies deemed clinically heterogenous were synthesized descriptively. 89% of the 62 studies included overall were cohort studies, 10% were randomized trials and 1 study was a combined cohort study with secondary analysis of a randomized trial.

Note Regarding Levels of Evidence in Prognostic Studies:
There are three types of studies mentioned here, described as follows:
  1. Phase I: Associations between potential prognostic factors and health outcomes are explored. Only crude (univariable) associations are reported.
  2. Phase II: Include the use of well-formulated comparison groups, stratified analyses, or multivariable analyses to identify sets of predictors.
  3. Phase III: The goal is to test specific hypotheses to confirm or disconfirm and independent relationship between an identified prognostic factor and a health outcome, while explicitly identifying and controlling for confounding.
Acute LBP
8 studies assessed pain outcomes (3 included in meta-analysis). The results suggest that depressive symptoms were associated with pain intensity but not pain trajectory. Depressive symptoms were associated with higher odds of pain (3 studies, 487 participants, odds ratio [OR] = 1.15, 95% CI 0.97–1.36, I2 = 78.67%). When one study deemed to have a high risk of bias was excluded, the association became non-significant (2 studies, 314 participants, OR = 1.05, 95% CI 0.97–1.15, I2 = 35.09%). One study found that a diagnosis of major depression was associated with higher pain intensity (OR range: 2.42-12.71).

Self-Reported Disability:
7 studies reported self-reported disability. 5 reported a positive association with depressive symptoms (β = 0.20, 95% CI 0.04–0.36), suggesting that depressive symptoms are associated with self-reported disability in patients with LBP.

5 studies examined LBP recovery (based on pain and disability measures). Four phase I studies showed varying results, while one phase II study showed that depressive symptoms were associated with a slower recovery time (hazard ratio [HR] = 0.94, 95% CI 0.91–0.97).

Work-Related Outcomes:
4 studies reported work-related outcomes, of which 4 were included in the meta-analysis. No association between depressive symptoms and work non-participation was noted (4 studies, 1356 participants, OR = 0.92, 95% CI 0.84–1.01, I2 = 93.46%). Excluding one high risk of bias study did not change this result (3 studies, 1035 participants, OR = 0.96, 95% CI 0.92–1.00, I2 = 75.70%). The general evidence suggests that depressive symptoms are not associated with work-related outcomes in patients with LBP.

Traffic Injury-Related Outcomes:
One phase II study suggested that depressive symptoms are associated with slower time-to-claim-closure in patients whose LBP is related to a motor vehicle accident (3232 participants; HR ranged 0.62–0.70).

Healthcare Utilization:
2 studies assessed healthcare utilization and found that depressive symptoms were associated with the rate of LBP-related primary care visits over a 1-year period (rate ratio = 1.04, 95% CI 1.02–1.07). A diagnosis of depression was associated with all-cause in-patient admissions (OR = 1.27, 95% CI 1.13–1.46), although no association with musculoskeletal-related inpatient admissions was noted.

Chronic LBP:
12 studies reported chronic pain outcomes; 3 were eligible for meta-analysis. No association between depressive symptoms and pain intensity were noted (3 studies, 2902 participants, β = 0.11, 95% CI 0.05–0.17, I2 = 1.04%). Of 5 phase II studies, 3 noted that depressive symptoms were associated with higher pain intensity (relative risk [RR] = 1.47, 95% CI 1.13–1.94), lower odds of pain reduction (OR = 0.47, 95% CI 0.25–0.89), and shorter duration of pain reduction (HR = 2.97, 95% CI 1.32–6.65). No association was noted between widespread chronic pain and depressive symptoms (OR = 1.01, 95% CI not reported, p > 0.05).

Self-Reported Disability:
10 studies reported self-reported disability, of which 5 were pooled for meta-analysis. 5 studies noted a significant association between depressive symptoms and LBP (5 studies, 3549 participants, β = 0.16, 95% CI 0.04–0.29, I2 = 74.69%). Excluding one study with high risk of bias did not change the trend (4 studies, 3065 participants, β = 0.15, 95% CI 0.02–0.27, I2 = 78.70%). 3 phase II studies noted a similar association with self-reported disability (RR = 1.34, 95% CI 1.04–1.72) and family/social disability (β = 1.94, 95% CI 1.27–2.60).

Health-Related Quality of Life (HRQoL):
6 studies reported data on HRQoL, with no association noted with depressive symptoms (2 studies, 637 participants, β = 1.09, 95% CI −1.83 to 4.02, I2 = 96.22%). One study found that depressive symptoms were associated with lower odds of improvement in mental HRQoL scores, suggesting that the overall results are inconclusive.

4 studies reported on recovery, using pain and disability scores. Pooled results from 2 studies found that depressive symptoms are associated with a worse recovery (2 studies, 13 263 participants, RR = 0.91, 95% CI 0.88–0.95, I2 = 0%).

Work-Related Outcomes:
3 studies found that depressive symptoms were not associated with work status.

Healthcare Utilization (Opioids):
2 studies assessed opioid use, with 1 study finding no association between depressive symptoms and continued opioid use, while another study reported increased odds of opioid use (OR = 1.65, 95% CI 0.97–2.81).

Lumbar Radiculopathy:
5 studies evaluated lumbar radiculopathy, with 1 study finding an association between depressive symptoms and radiculopathy (> 6 months’ duration).

LBP with Index Healthcare Visit:
3 studies found that depressive symptoms were associated with poor tolerance of symptom severity (OR = 2.3, 95% CI 1.4–3.6) and with higher pain intensity, disability and worse recovery (OR range: 1.1-2.3).

Other LBP Populations

2 studies examined LBP in occupational settings. One found no association between depressive symptoms and work retention in patients on restricted duty, while another reported that in patients on sick leave for LBP, depressive symptoms were associated with reduced HRQoL, but not return-to-work or pain.

Clinical Application & Conclusions:

These authors found exploratory evidence (i.e. Phase I and II prognostic factor studies) that depressive symptoms are associated with self-reported disability, worse recovery and slower traffic injury-related claim closure, but not associated with pain or work-related outcomes in patients suffering from acute LBP. Additionally, healthcare utilization was greater in those with depressive symptoms with acute LBP (Phase III confirmatory evidence). In patients with chronic LBP, depressive symptoms are associated with higher pain intensity, disability and worse recovery, but not incident widespread chronic pain. This evidence was exploratory in nature. While more work and confirmatory (Phase III) studies are needed, this evidence provides valuable information on prognostic factors for LBP in patients with depressive symptoms.

Study Methods:

Searched databases included: MEDLINE, Embase, CINAHL, and PsycINFO from inception to June 25, 2020. Search terms for both subject headings and free-text words included: low back pain, psychological factors, and depressive symptoms and/or depression.

Eligibility Criteria
  • Population: Studies including patients aged 16 or older with non-specific LBP with or without radiculopathy.
  • Exposure: Patients diagnosed with depression or depressive symptoms (i.e., self-reported symptoms of depression such as feeling down, depressed, or hopeless) were required for study inclusion.
  • Outcomes: Eligible studies must have included one of the following outcomes: pain, disability, overall health status, satisfaction with care and healthcare utilization. Additionally, eligible studies were published in English. Guidelines, letters, editorials, etc. were excluded from the review.
Study Selection
Paired reviewers independently screened citations to determine study eligibility. Disagreements were moderated through discussion, with a third reviewer available if consensus could not be reached.

Data Collection
Extracted data included: author, year, study design, setting, patient characteristics, duration of follow-up, exposure and outcomes definitions and estimates of effect. Two reviewers independently extracted study results for effects estimates. For all other data, the lead author extracted data, which was verified by a second reviewer.

Methodological Quality Appraisal
Study quality was evaluated using the Quality in Prognosis Studies (QUIPS) tool.

Inter-rater agreement was assessed using the kappa coefficient. Study heterogeneity was assessed using the I2 statistic. Results were stratified based on LBP type (ex. LBP with or without radiculopathy) and duration, exposure and health outcomes. A random effects approach was used during the meta-analysis. The meta-analysis was performed first with all eligible studies included and then repeated with studies with high risk of bias excluded.

Study Strengths / Weaknesses:

  • This review project was planned a priori with the methods published based on the Cochrane Prognosis Methods Group.
  • The authors followed PRISMA guidelines and pooled eligible data based on specific criteria to assess heterogeneity.
  • Only English language studies were included.
  • Heterogeneity between studies impacted the results for some outcomes (ex. HRQoL).
  • Insufficient data resulted in no evaluation of publication bias.

Additional References:

  1. Wu A, March L, Zheng X et al. Global low back pain prevalence and years lived with disability from 1990 to 2017: estimates from the Global Burden of Disease Study 2017. Ann Transl Med 2020; 8(6); 299.
  2. Cassidy JD, Carroll LJ, Côté P. The Saskatchewan health and back pain survey. The prevalence of low back pain and related disability in Saskatchewan adults. Spine (Phila Pa 1976). 1998; 23(17): 1860-6; discussion 7.
  3. Cassidy JD, Côté P, Carroll LJ, Kristman V. Incidence and course of low back pain episodes in the general population. Spine (Phila Pa 1976). 2005; 30(24): 2817-23.
  4. Hincapie CA, Cassidy JD, Côté P, Carroll LJ, Guzman J. Whiplash injury is more than neck pain: a population-based study of pain localization after traffic injury. J Occup Environ Med 2010; 52(4): 434-40.
  5. Global Burden of Disease 2015 Disease and Injury Incidence and Prevalence Collaborators, et al. Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet 2016; 388(10053): 1545-602.
  6. Green BN, Johnson CD, Haldeman S et al. A scoping review of biopsychosocial risk factors and comorbidities for common spinal disorders. PLoS One 2018; 13(6): e0197987.
  7. Patten SB, Williams JV, Wang J. Mental disorders in a population sample with musculoskeletal disorders. BMC Musculoskelet Disord 2006; 737.
  8. Ha JY, Kim ES, Kim HJ, Park SJ. Factors associated with depressive symptoms in patients with chronic low back pain. Ann Rehabil Med 2011; 35(5): 710-8.
  9. McGowan J, Sampson M, Salzwedel DM et al. PRESS Peer Review of Electronic Search Strategies: 2015 Guideline Statement. J Clin Epidemiol 2016; 7540-6.
  10. Bener A, Dafeeah EE, Salem MO. Determinants of depression and somatisation symptoms in low back pain patients and its treatment: global burden of diseases. J Pak Med Assoc 2015; 65(5): 473-9.
  11. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 2018; 392(10159): 1789-858.
  12. Iles RA, Davidson M, Taylor NF. Psychosocial predictors of failure to return to work in non-chronic non-specific low back pain: a systematic review. Occup Environ Med 2008; 65(8): 507-17.
  13. Steenstra IA, Munhall C, Irvin E et al. Systematic review of prognostic factors for return to work in workers with subacute and chronic low back pain. J Occup Rehabil 2017; 27(3): 369-81.
  14. Ramond A, Bouton C, Richard I et al. Psychosocial risk factors for chronic low back pain in primary care–a systematic review. Fam Pract 2011; 28(1): 12-21.
  15. Pinheiro MB, Ferreira ML, Refshauge K, Maher CG, Ordonana JR, Andrade TB, Tsathas A, Ferreira PH. Symptoms of depression as a prognostic factor for low back pain: a systematic review. Spine J 2016; 16(1): 105-16.
  16. Alhowimel A, Al Otaibi M, Radford K, Coulson N. Psychosocial factors associated with change in pain and disability outcomes in chronic low back pain patients treated by physiotherapist: a systematic review. SAGE Open Med 2018; 62050312118757387.
  17. Hayden JA, van der Windt DA, Cartwright JL, Côté P, Bombardier C. Assessing bias in studies of prognostic factors. Ann Intern Med 2013; 158(4): 280-6.

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