An Update on the Effect of Physical Exercise on Depressive Disorder: A Systematic Review with Meta-Analysis and Meta-Regression of Randomized Controlled Trials

<b>Background</b>: Physical exercise (PE) has emerged as a promising intervention for depressive disorder (DD), yet its efficacy and optimal implementation remain under investigation. Objective: To thoroughly assess the effectiveness of supervised PE as a conventional intervention for adults with DD. <b>Methods</b>: A comprehensive literature search was conducted across PubMed/MEDLINE, EBSCOhost, Ovid, Web of Science, and Scopus. Randomized controlled trials (RCTs) published between 2010-2025 involving adults with DD without other comorbidities under supervised exercise interventions were selected. Methodological rigor was ensured through two independent reviewers and adherence to PRISMA 2020 guidelines. The influence of moderating variables [total work performed (workload) and the instrument used to evaluate DD (instrument)] was analyzed using meta-regression. The pooled effect size was estimated using both frequentist and Bayesian meta-analyses. <b>Results</b>: From 15,542 screened records, 20 RCTs were selected. Workload and instrument account for 60% and 15% of the variance in the effect size, respectively. Both frequentist and Bayesian meta-analyses showed that supervised PE reduces depressive symptoms (standardized mean difference = 0.82; 95% CI: 0.54-1.11; I² = 76%, and 0.61; 95% CI: -0.06-0.95; I² = 51, respectively). <b>Conclusions</b>: PE could be a valuable complementary intervention to reduce depressive symptoms in adults with depression. PROSPERO (CRD420251121919).