title: Antidepressant Efficacy of Adjunctive Aerobic Activity and Associated Biomarkers in Major Depression: A 4-Week, Randomized, Single-Blind, Controlled Clinical Trial.
abstract: Major depressive disorder (MDD) is a highly prevalent, heterogeneous and systemic medical condition. Treatment options are limited, and recent studies have suggested that physical exercise can play an important role in the therapeutics of MDD. The aim of this study was to evaluate the antidepressant efficacy of adjunctive aerobic activity in association with pharmacotherapy (selective serotonin reuptake inhibitor) in symptomatic MDD as well as its association with physiological biomarkers.
  
  
  
  In this randomized, single-blind, add-on, controlled clinical trial, 57 patients (18-55 years of age) were followed-up for 28 days. All patients were drug-free, had been diagnosed with symptomatic MDD and received flexible dose of sertraline during the trial. Patients were randomized to either a 4-week program (4x/week) of add-on aerobic exercise (exercise group, N = 29) or no activity (control group, N = 28). Depression severity was assessed using the Hamilton Rating Scale for Depression (HAM-D) as the primary outcome. At baseline and endpoint, all patients underwent a comprehensive metabolic/cardiopulmonary exercise testing-including determination of maximal oxygen uptake (VO2max), VO2 at the second ventilatory threshold (VO2-VT2), and oxygen pulse (O2 pulse).
  
  
  
  Depression scores significantly decreased in both groups after intervention. Importantly, patients in the aerobic exercise group required lower sertraline dose compared to the control group (sertraline monotherapy). The VO2max and O2 pulse parameters increased over time only in the exercise group and remained unchanged in the control group.
  
  
  
  The present findings suggest that a 4-week training of aerobic exercise significantly improves functional capacity in patients with MDD and may be associated with antidepressant efficacy. This approach may also decrease the need for higher doses of antidepressants to achieve response. Further studies in unmedicated and treatment-resistant MDD patients are needed in order to confirm the utility of short-term aerobic exercise as an alternative therapeutic approach in MDD.
  
  
  
  ClinicalTrials.gov NCT02427789.
authors.affiliation: Laboratory of Neuroscience LIM-27, Institute and Department of Psychiatry, University of Sao Paulo, Sao Paulo, Sao Paulo, Brazil.
authors.forename: Cristiana Carvalho
authors.initials: CC
authors.lastname: Siqueira
authors.affiliation: Laboratory of Neuroscience LIM-27, Institute and Department of Psychiatry, University of Sao Paulo, Sao Paulo, Sao Paulo, Brazil.
authors.forename: Leandro L
authors.initials: LL
authors.lastname: Valiengo
authors.affiliation: Department of Clinical Medicine and Translational Psychiatry Research Group, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil.
authors.forename: André F
authors.initials: AF
authors.lastname: Carvalho
authors.affiliation: Laboratory of Movement Studies, University of Sao Paulo School of Medicine Hospital das Clínicas, Sao Paulo, Sao Paulo, Brazil.
authors.forename: Paulo Roberto
authors.initials: PR
authors.lastname: Santos-Silva
authors.affiliation: Mood Disorders Unit (GRUDA), Institute and Department of Psychiatry, University of Sao Paulo, Sao Paulo, Sao Paulo, Brazil.
authors.forename: Giovani
authors.initials: G
authors.lastname: Missio
authors.affiliation: Laboratory of Neuroscience LIM-27, Institute and Department of Psychiatry, University of Sao Paulo, Sao Paulo, Sao Paulo, Brazil.|Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health (NIMH), Bethesda, Maryland, United States of America.
authors.forename: Rafael T
authors.initials: RT
authors.lastname: de Sousa
authors.affiliation: Laboratory of Neuroscience LIM-27, Institute and Department of Psychiatry, University of Sao Paulo, Sao Paulo, Sao Paulo, Brazil.
authors.forename: Georgia
authors.initials: G
authors.lastname: Di Natale
authors.affiliation: Laboratory of Neuroscience LIM-27, Institute and Department of Psychiatry, University of Sao Paulo, Sao Paulo, Sao Paulo, Brazil.|Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of Sao Paulo, Sao Paulo, Sao Paulo, Brazil.
authors.forename: Wagner F
authors.initials: WF
authors.lastname: Gattaz
authors.affiliation: Mood Disorders Unit (GRUDA), Institute and Department of Psychiatry, University of Sao Paulo, Sao Paulo, Sao Paulo, Brazil.
authors.forename: Ricardo Alberto
authors.initials: RA
authors.lastname: Moreno
authors.affiliation: Laboratory of Neuroscience LIM-27, Institute and Department of Psychiatry, University of Sao Paulo, Sao Paulo, Sao Paulo, Brazil.|Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health (NIMH), Bethesda, Maryland, United States of America.|Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of Sao Paulo, Sao Paulo, Sao Paulo, Brazil.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Machado-Vieira
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000378:metabolism*; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000378:metabolism; D015444:Exercise; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D016037:Single-Blind Method; D055815:Young Adult
chemical_list: D015415:Biomarkers; D017367:Selective Serotonin Reuptake Inhibitors