Effects of antidepressant drug therapy with or without physical exercise on inflammatory biomarkers in major depressive disorder: a systematic review and meta-analysis of randomized controlled trials

Abstract

Objective To conduct a systematic review and meta-analysis of the effects of antidepressant drug therapy (with or without physical exercise) on peripheral inflammatory markers in patients with major depressive disorder (MDD). Methods MEDLINE, PyscINFO, Embase, and Google Scholar databases were searched until May 2020. Randomized trials that measured at least one inflammatory biomarker and included adult outpatients with MDD under antidepressant drug therapy (any drug) with or without physical exercise (any modality) were eligible. Results were summarized using the standardized mean difference (SMD) with 95% confidence intervals (95% CI) under a random-effects model. The Cochrane risk of bias tool (2010) was used to evaluate the risk of bias in the included trials. Results Sixty-three trials were identified, encompassing data from 3482 patients, and 20 investigated biomarkers. Trials had biases across multiple domains, rising concerns primarily to selection bias/performance bias/detection bias/attrition bias. SMDs between pre-and post-results indicated a significant reduction in the levels of IL-2 (SMD, − 0.25; 95% CI, − 0.41 to − 0.09, P = 0.002), IL-6 (SMD, − 0.19; 95% CI, − 0.35 to − 0.025, P = 0.024), IL-10 (SMD, − 0.32; 95% CI, − 0.57 to − 0.07, P = 0.011), and serum cortisol (SMD, − 0.35; 95% CI, − 0.58 to − 0.12, P = 0.002). Evidence supporting the influence of physical exercise combined with antidepressant drugs on peripheral inflammatory markers in MDD is sparse and heterogeneous. Conclusion There is some evidence that antidepressant drug therapy is associated with an overall positive reduction in inflammatory markers, but the evidence is heterogeneous. Further research linking how inflammatory biomarkers modulate physiology related to antidepressant response is required.

Neural, Anti-Inflammatory, and Clinical Effects of Transauricular Vagus Nerve Stimulation in Major Depressive Disorder: A Systematic Review

“…After the initiation, several studies, including those examining the levels of CRP, TNF-α, and interleukins, were conducted to explain the relationship between inflammation and MDD ( Dowlati et al, 2010 ; Osimo et al, 2020 ). Moreover, the effects of antidepressants on inflammation or the effects of anti-inflammatory drugs on MDD have also been investigated ( Köhler et al, 2014 ; Fernandes et al, 2022 ).…”

Physical Exercise and Major Depressive Disorder in Adults: Systematic Review and Meta-analysis

“…These reviews suggest that exercise reduce the symptomatology of MDD. However, some of these reviews do not provide the classi cation of evaluation, development, and assessment of recommendations (GRADE) [2,12,16,20], and in others they found a level of certainty of their results that varies between moderate and very low quality [2-4, 17, 18].…”

“…In fact, MDD is the leading cause of suicide deaths, with an incidence of up to 800,000 annually around the world [11]. Furthermore, it has become an independent risk factor for all-cause mortality [12]. Consequently, before the SARS-CoV-2 pandemic, MDD was the second leading cause of disability worldwide [8].…”

Plasma Phosphoethanolamine Levels as a Biomarker for Monitoring Major Depressive Disorder

“…Some of the potential biomarkers of MDD that have been studied include brain imaging biomarkers of changes in brain structure and function, namely, functional magnetic resonance imaging (fMRI) and positron emission tomography (PET), in which abnormalities in speci c brain regions such as the prefrontal cortex, hippocampus, and amygdala are associated with MDD [4][5][6][7] . Additionally, in ammatory biomarkers, including C-reactive protein (CRP) and in ammatory cytokine markers, have been observed in some depressed patients [7][8][9][10][11][12][13][14] . Although strongly in uenced by a variety of environmental factors, genetic markers (i.e., speci c genetic variants and polymorphisms) have been implicated in an increased risk of MDD 15 .…”