Impact of Depression on Postoperative Medical and Surgical Outcomes in Spine Surgeries: A Systematic Review and Meta-Analysis

Introduction: The relationship between psychiatric disorders, including depression, and invasive interventions has been a topic of debate in recent literature. While these conditions can impact the quality of life and subjective perceptions of surgical outcomes, the literature lacks consensus regarding the association between depression and objective perioperative medical and surgical complications, especially in the neurosurgical domain. Methods: MEDLINE (PubMed), EMBASE, PsycINFO, and the Cochrane Library were queried in a comprehensive manner from inception until 10 November 2023, with no language restrictions, for citations investigating the association between depression and length of hospitalization, medical and surgical complications, and objective postoperative outcomes including readmission, reoperation, and non-routine discharge in patients undergoing spine surgery. Results: A total of 26 articles were considered in this systematic review. Upon pooled analysis of the primary outcome, statistically significantly higher rates were observed for several complications, including delirium (OR:1.92), deep vein thrombosis (OR:3.72), fever (OR:6.34), hematoma formation (OR:4.7), hypotension (OR:4.32), pulmonary embolism (OR:3.79), neurological injury (OR:6.02), surgical site infection (OR:1.36), urinary retention (OR:4.63), and urinary tract infection (OR:1.72). While readmission (OR:1.35) and reoperation (OR:2.22) rates, as well as non-routine discharge (OR:1.72) rates, were significantly higher in depressed patients, hospitalization length was comparable to non-depressed controls. Conclusions: The results of this review emphasize the significant increase in complications and suboptimal outcomes noted in patients with depression undergoing spinal surgery. Although a direct causal relationship may not be established, addressing psychiatric aspects in patient care is crucial for providing comprehensive medical attention.


Introduction
Depression is a complex and multifaceted mental disorder, which is distinguished by enduring feelings of sadness, despair, and a diminished interest in activities that were once pleasurable [1].Its impact extends beyond the emotional realm, influencing physical health and potentially intersecting with the outcomes of various medical interventions.Depression can lead to a wide array of physical problems and increase the risk for or worsen certain physical illnesses or conditions [2].A significant proportion of patients complaining of symptoms such as lower back pain need to undergo different types of spine surgeries.A diverse array of procedures such as laminectomy, discectomy, kyphoplasty, and lumbar spinal fusion address a spectrum of spinal disorders.Within the surgical context, depression has been linked to unfavorable postoperative results, such as heightened morbidity and mortality rates [3].Interestingly, previous research has shown that patients with spinal deformities, specifically, have demonstrated a heightened susceptibility to depression when compared to the broader population [4].Moreover, there is evidence suggesting that depression adversely impacts patient outcomes following lower back surgery [5,6].Nevertheless, there is a scarcity of research investigating the effects of comorbid psychiatric conditions on different postoperative outcomes such as perioperative adverse events, surgical site and systemic infections, length of stay in the hospital, and surgical and medical readmission.Understanding the influence of depression on the clinical outcomes of spine surgeries is crucial since a deeper understanding of this relationship can inform the development of targeted perioperative strategies, with the potential to reduce complications and enhance overall patient care and satisfaction.Although the expected correlation of preoperative depression with postoperative self-reported quality of life and patient disability outcomes in spinal surgeries have been recently investigated [7], the impact of depression on medical and surgical outcomes is not thoroughly understood and is further explored in a quantitative manner in this review.

Protocol and Registration
This systematic review and meta-analysis adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [8].The review protocol was registered with PROSPERO (CRD42024513255).

Eligibility Criteria
Studies were included if they met the following criteria: (1) peer-reviewed articles published in English; (2) studies that included patients undergoing spinal surgery; (3) studies that assessed preoperative depression status in patients undergoing spine surgery; and (4) studies that reported on postoperative surgical and medical outcomes, including but not limited to mortality, non-routine discharge, overall complications, readmission, reoperation, and length of stay.Excluded were case reports, conference abstracts, reviews, and studies not reporting on the specific outcomes of interest.Studies restricted to reporting self-reported quality of life and disability questionnaires were also excluded.

Search Strategy and Data Collection
A comprehensive search was conducted in MEDLINE (PubMed), EMBASE, PsycINFO, and the Cochrane Library from inception until 10 November 2023, with no language restrictions.The following search strategy was used: (Depress* OR Depressive neurosis) AND ((Spin* surgery) OR SCS OR (Spinal cord surgery) OR (Lumbar Surgery) OR Kyphoplasty OR Vertebroplasty OR (Vertebral column resection) or VCR) AND (Outcome OR prognos* OR function OR readmission OR reoperation OR complication OR Mortality OR death OR quality).Reference lists of included studies and relevant reviews were screened to identify additional studies.
Two reviewers independently screened titles and abstracts to determine eligibility.Full texts of potentially eligible studies were then retrieved and assessed for inclusion by the same reviewers.Any discrepancies were resolved through discussion or consultation with a third reviewer.A standardized data extraction form was employed to gather information from each included study regarding study characteristics (author, year, country), participant characteristics (sample size, age), details of the spinal surgery, methods of depression assessment, and postoperative outcomes.Data extraction was performed independently by two reviewers, with discrepancies resolved by consensus or involvement of a third reviewer.
The quality of included studies was assessed using the Newcastle-Ottawa assessment tool [9].Similarly, two reviewers independently assessed the risk of bias, with any discrepancies resolved through discussion or consultation with a third reviewer.

Data Synthesis and Analysis
A quantitative synthesis was conducted using aggregated participant data, requiring at least two studies for outcome analysis.A random-effects model was employed to account for the varying designs and populations of the included studies.Secondary subgroup analysis was performed to distinguish deep from superficial surgical site infections and to categorize readmission rates based on the assessment interval.Study heterogeneity was assessed with the I 2 or Q test.Effect measures were calculated for odds ratios and mean ratios.The primary outcome was the number of participants experiencing adverse events or medical/clinical complications, as defined by each study.Secondary outcomes included the length of hospital stay, non-routine discharge, readmission, reoperation, and mortality rate.Each outcome was analyzed through a generic inverse variance meta-analysis to pool studies on individual complications.The measure of effect for binary outcomes was chosen as odds ratios, either calculated via contingency tables or directly extracted from the studies.The standard error of the odds ratios reported in each study were back-calculated using the 95% confidence intervals in Stata Statistical Software (Release 17, College Station, TX, USA: StataCorp LLC).

Results
The initial search yielded 1547 citations, out of which 127 underwent full-text screening (Figure 1).In total, 26 were included in this systematic review .While most of the studies were rated high in terms of quality as assessed by the Newcastle-Ottawa scale (Supplementary Materials), the majority failed to adequately define and describe the diagnostic criteria for depression in the included studies.The majority of studies included patients undergoing surgery for degenerative spinal diseases (Table 1).
Studies reported various postoperative outcomes, including the rates of adverse events (such as surgical site and nonsurgical infections, and cardiovascular complications), nonroutine discharges (to rehabilitation facilities or with external services), hospitalization duration, readmissions, and reoperation rates.The number of studies evaluating mortality was insufficient for a quantitative analysis.Although not selected as pooled outcomes, Huang et al. and Schoell et al. found higher rates of ventilator use and failed back surgery syndrome, respectively [25,31].Moreover, Holbert et al. identified a higher risk of short-term emergency visits, readmissions, and complications.However, their study was excluded from this meta-analysis due to the concurrent inclusion of patients with anxiety [24].

Primary Outcome
The meta-analysis revealed higher odds of multiple complications in patients with depression (Table 2).The pooled data demonstrated a significant association between depression and postoperative delirium (Odds Ratio Although there was a trend toward statistical significance, the rates of sepsis/infection, myocardial infarction, and pneumonia were not distinctly different between the two groups (see Supplementary Materials).

Discussion
The World Health Organization considers major depressive disorder as the fourth leading cause of morbidity, which is projected to become the second leading cause of disability by 2030 [36].The long-term implications of mental health on surgical outcomes highlight the imperative need for integrated mental health assessments and targeted interventions to mitigate the adverse effects of depression and enhance overall patient care.The findings of our study underscore the significant impact of depression on the clinical

Discussion
The World Health Organization considers major depressive disorder as the fourth leading cause of morbidity, which is projected to become the second leading cause of disability by 2030 [36].The long-term implications of mental health on surgical outcomes highlight the imperative need for integrated mental health assessments and targeted interventions to mitigate the adverse effects of depression and enhance overall patient care.The findings of our study underscore the significant impact of depression on the clinical outcomes of spine surgeries.Patients with depression exhibited a heightened susceptibility to a range of complications, including delirium, deep vein thrombosis (DVT), fever, hematoma, hypotension, sensory deficit, surgical site infection, urinary retention, and and a higher likelihood of hospital readmission, extended length of hospital stay and a twofold increased risk of reoperation among depressed patients suggesting a slower and potentially more challenging recovery process.
Although the causal association between these factors was not explored in the studies included in this review, the literature offers intriguing insights into the relationship between depression and surgical outcomes through various interconnected mechanisms.Preoperative depression may compromise patients' motivation for engaging in essential physical and social activities crucial for maintaining or regaining functional capacity.This diminished motivation often translates into challenges in effectively participating in physical therapy, a cornerstone for functional recovery after spine surgery.Deteriorating baseline health status in these patients can be further exacerbated by higher rate of comorbid disorders.Indeed, Poorman et al. reported higher rate of osteoporosis, rheumatoid arthritis, and connective tissue disorders in patients undergoing surgery for cervical deformity [37].Furthermore, depressive symptoms can influence patients' adherence to prescribed medical regimens, affecting their biological milieu through neuroendocrine and inflammatory mechanisms [38,39].This not only impedes the healing process but may also contribute to heightened susceptibility to complications.
Depression may also significantly influence a patient's perception of self-efficacy, limiting their active involvement in medical care, rehabilitation programs, and social activities-all integral components for optimizing functional recovery post-spine surgery.Beyond behavioral and psychological aspects, the intricate relationship between depression and the immune system, including the pro-inflammatory milieu caused by psychological stress, diminished T-cell response and the shift away from Thelper-1 phenotype, and the immunosuppressive effects of certain antidepressant medications [3,40,41], may elaborate on the increased risk of postoperative SSI and systemic infections.Additionally, epidemiological studies indicate that mood disorders are linked to an increased body mass index, hypertension, elevated cholesterol levels, diabetes, lack of physical activity, and consistent engagement in smoking and nicotine dependence [42].Understanding these multifaceted pathways is essential for devising comprehensive strategies to address preoperative depression and enhance overall patient outcomes in the surgical setting.
Two preceding systematic reviews have investigated the correlation between preoperative depression and the outcomes of spine surgeries, offering diverse perspectives on this intricate interconnection.One review posits that the degree of improvement is similar when comparing groups with and without depression; however, individuals with depression reported a more pronounced level of pain [7].Notably, our research deviates by scrutinizing distinct, more objectively measurable results.The review conducted by Javeed et al. asserts a direct link between preoperative depression and unfavorable quality of life and disability outcomes [7].Mollon et al. [43] and Häuser et al. [44] independently validated that preoperative depression significantly associates with increased rates of postoperative complications.Additionally, Mollon et al. underscored that individuals with a history of depression are more prone to postoperative adverse events such delirium, infections, and anemia necessitating blood transfusion.Interestingly, there was no statistically significant difference in in-hospital death rates.On the other hand, depressed patients had slightly prolonged hospital stays and had a higher likelihood of non-routine discharge.Furthermore, Adogwa et al. [10] identified a correlation between depression and the 30-day readmission rate.Another cohort study by Chaichana et al. [45] affirmed the impact of preoperative depression and heightened somatic awareness on the probability of achieving clinically meaningful improvements in disability or quality of life.These cumulative findings underscore the intricate and multifaceted nature of the association between preoperative depression and outcomes in spine surgeries.
The profound impact of depression on surgical outcomes enables the creation of collaborative care models, uniting surgical teams, anesthesiologists, and mental health professionals to optimize patient preparation and facilitate a more holistic recovery process [18,46].While short-term interventions in the perioperative may not significantly reduce depressive symptomatology, targeted psychosocial interventions for high-risk patients identified using concise screening tools like the 9-item Patient Health Questionnaire-9 (PHQ-9) and the 14-item Hospital Anxiety and Depression Scale (HADS) will not only enable better assessment of postoperative complication risks but also positively impact surgical outcomes.Recent literature indicates that this approach may have successfully reduced adverse outcomes, including medical complications, even though the rate of readmission remained similar.This is based on a retrospective study examining the impact of preoperative depression screening and psychotherapy visits for patients with a history of depression undergoing short-segment lumbar fusion [47].Moreover, the heightened risk in patients with depressive phenotypes may be secondary to poor overall health linked to impaired mental well-being, rather than the psychosomatic manifestation of the disease.This necessitates a more rigorous approach to preoperative testing for spinal surgery in these subsets of patients.
Acknowledging several limitations in this review is crucial.Despite a significantly higher risk of complications, the lack of association between depression and adverse events may be attributed to varying definitions and the limited number of studies focusing on distinct complications.Additionally, the discrepancy could stem from clustered complications in depressed patients, leading to a similar overall complication rate but a higher comorbidity rate.Data scarcity comparing medicated and non-medicated depressed patients hinders comprehensive conclusions.Moreover, the absence of detailed information on surgery-related factors and comorbid conditions introduces potential confounding variables.Heterogeneous depression screening methods and the inclusion of various surgeries add result variability.Lastly, the predominance of cohort studies underscores the need for cautious interpretation.Nevertheless, the need for further research is evident.Future studies with a focus on specific types of surgeries and a larger cohort of patients are imperative to refine our insights and enhance the precision of interventions.This study serves as a stepping stone, emphasizing the ongoing importance of exploring the nuanced interplay between mental health and surgical outcomes for the advancement of patient care strategies in diverse surgical contexts.

Supplementary Materials:
The following supporting information can be downloaded at: https: //www.mdpi.com/article/10.3390/jcm13113247/s1,Table S1: Risk of bias and quality assessment using Newcastle-Ottawa scale.Forest plots for perioperative complications analyses are available in Funding: This study did not receive funding, grants, or sponsorship from any individuals or organization.
Institutional Review Board Statement: Ethical review and approval were waived for this study due to the systematic review formatting of this work.

Figure 1 .
Figure 1.PRISMA flowchart illustrating the study screening and inclusion process.

Figure 1 .
Figure 1.PRISMA flowchart illustrating the study screening and inclusion process.

Table 1 .
Description and summary of the included studies.

Table 2 .
The pooled analyses evaluating the association between depression and postoperative medical and surgical complications.The bold estimates were statistically significant for each analysis.