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Randomized Controlled Trial
. 2025 Jan:123:876-883.
doi: 10.1016/j.bbi.2024.10.033. Epub 2024 Oct 28.

Running therapy or antidepressants as treatments for immunometabolic depression in patients with depressive and anxiety disorders: A secondary analysis of the MOTAR study

Sarah R Vreijling  1 , Brenda W J H Penninx  2 , Josine E Verhoeven  3 , Charlotte E Teunissen  4 , Elena R Blujdea  4 , Aartjan T F Beekman  5 , Femke Lamers  6 , Rick Jansen  2
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Free article
Randomized Controlled Trial

Running therapy or antidepressants as treatments for immunometabolic depression in patients with depressive and anxiety disorders: A secondary analysis of the MOTAR study

Sarah R Vreijling et al. Brain Behav Immun. 2025 Jan.
Free article

Abstract

Background: Exercise promotes immunometabolic health and is increasingly recognized as an effective depression treatment. Exercise may be beneficial for patients with immunometabolic depression (IMD), who experience inflammatory and metabolic dysregulations and may respond less to antidepressants. This secondary analysis of the MOTAR study compared the effects of running therapy and antidepressants on IMD features among patients with depression and/or anxiety disorder. We additionally assessed whether baseline IMD moderated intervention effects on depression.

Methods: Participants received 16 weeks of group-based running therapy (N = 96) or escitalopram/sertraline (N = 45) in a partially randomized patient preference design. IMD features included atypical, energy-related symptom (AES) severity, inflammation index (CRP, IFN-γ, IL-6, TNF-α), metabolic syndrome index, three metabolite principle components (PC) (derived from 73 metabolites) and a composite IMD index.

Results: Interventions differed in changes in the metabolic syndrome index (d = 0.59, p = 0.026) and IMD index (d = 0.85, p < 0.001). While running therapy decreased both outcomes, the antidepressant group showed an increased IMD index. Although groups did not differ statistically significant in changes in AES severity, inflammation index, and metabolite PC1, results indicated a consistent trend towards greater improvement with running therapy across these outcomes as well (d = 0.38 to 0.52). Baseline IMD did not moderate intervention effects on depression outcomes.

Conclusions: This study suggests that exercise more effectively targets the IMD dimension than antidepressants. Patients with IMD did not benefit more from running therapy than antidepressants in terms of reductions in depression. Exercise should be considered an alternative or complementary treatment to particularly reduce IMD features in depressed patients.

Trial registration: Trialregister.nl Number of identification: NTR3460.

Keywords: Antidepressants; Depression; Exercise; Inflammation; Metabolism; Running therapy.

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Conflict of interest statement

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: CET has research contracts with Acumen, ADx Neurosciences, AC-Immune, Alamar, Aribio, Axon Neurosciences, Beckman-Coulter, BioConnect, Bioorchestra, Brainstorm Therapeutics, Celgene, Cognition Therapeutics, EIP Pharma, Eisai, Eli Lilly, Fujirebio, Instant Nano Biosensors, Novo Nordisk, Olink, PeopleBio, Quanterix, Roche, Toyama, Vivoryon. She is editor in chief of Alzheimer Research and Therapy, and serves on editorial boards of Medidact Neurologie/Springer, and Neurology: Neuroimmunology & Neuroinflammation. She had consultancy/speaker contracts for Eli Lilly, Merck, Novo Nordisk, Olink and Roche. The other authors declare no conflicts of interest.

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