Antidepressant Pharmacotherapy and Structured Physical Activity in Major Depressive Disorder: Implications for Functional Capacity and Cardiometabolic Health
DOI:
https://doi.org/10.12775/QS.2026.52.69424Keywords
Major depressive disorder, Antidepressants, Physical activity, Exercise therapy, Cardiometabolic health, Functional capacity, Neuroplasticity, Metabolic syndromeAbstract
Major depressive disorder (MDD) is a multidimensional condition associated not only with affective symptoms but also with reduced physical activity, impaired functional capacity, and increased cardiometabolic risk. Beyond mood disturbance, depression is frequently accompanied by decreased cardiorespiratory fitness, altered body composition, and autonomic dysregulation. While antidepressant pharmacotherapy remains a cornerstone of treatment, structured physical activity has emerged as a clinically relevant intervention within sports and lifestyle medicine. Evidence from recent meta-analyses and network meta-analyses demonstrates moderate antidepressant effects of aerobic and resistance-based exercise interventions. Comparative analyses suggest similar efficacy of exercise and pharmacotherapy in mild-to-moderate depression, with structured training providing additional benefits for cardiovascular performance, metabolic regulation, and functional recovery. The bidirectional relationship between depression and metabolic syndrome further underscores the importance of addressing systemic risk factors alongside psychiatric symptoms. Antidepressant agents differ in their metabolic, autonomic, and endocrine profiles, with potential implications for weight regulation, insulin sensitivity, and exercise adherence. Overlapping biological mechanisms between pharmacotherapy and physical training include monoaminergic modulation, neuroplasticity enhancement through brain-derived neurotrophic factor pathways, and attenuation of systemic inflammation. However, direct randomized comparisons of combined pharmacotherapy and structured exercise remain limited. An individualized treatment model integrating pharmacological stabilization with progressive physical training may optimize both psychological recovery and longterm physiological resilience in patients with major depressive disorder.
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Copyright (c) 2026 Konrad Gronek, Edward Zheng, Agnieszka Olejnik, Maria Możdżan, Laura Biskup, Beata Huszcza, Julia Kaczmarek, Jakub Grandos, Dominik Gajewski, Zuzanna Głowacka, Kinga Kościołek
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