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Oxidative Medicine and Cellular Longevity
Volume 2012, Article ID 609421, 13 pages
Review Article

Preclinical and Clinical Evidence of Antioxidant Effects of Antidepressant Agents: Implications for the Pathophysiology of Major Depressive Disorder

1Mood Disorders Program and Women's Health Concerns Clinic, Department of Psychiatry and Behavioural Neurosciences, McMaster University, 301 James Street South, Suite F614, Hamilton, ON, Canada L8P 3B6
2Center of Oxidative Stress Research, Professor Tuiskon Dick Department of Biochemistry, Institute of Health Basic Sciences, Federal University of Rio Grande do Sul (UFRGS), Ramiro Barcelos Street, 2600 Anexo, 90035-003 Porto Alegre, RS, Brazil

Received 4 February 2012; Accepted 2 March 2012

Academic Editor: Daniel Pens Gelain

Copyright © 2012 Guilherme A. Behr et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Major depressive disorder (MDD) is a common mental disorder associated with a significant negative impact on quality of life, morbidity/mortality, and cognitive function. Individuals who suffer with MDD display lower serum/plasmatic total antioxidant potentials and reduced brain GSH levels. Also, F2-isoprostanes circulatory levels are increased in MDD subjects and are correlated with the severity of depressive symptoms. Urinary excretion of 8-OHdG seems to be higher in patients with MDD compared to healthy controls. Despite the fact that antidepressant drugs have been used for more than 50 years, their mechanism of action is still not fully understood. This paper examines preclinical (in vitro and animal model) and clinical literature on oxidative/antioxidant effects associated with antidepressant agents and discusses their potential antioxidant-related effects in the treatment of MDD. Substantial data support that MDD seems to be accompanied by elevated levels of oxidative stress and that antidepressant treatments may reduce oxidative stress. These studies suggest that augmentation of antioxidant defences may be one of the mechanisms underlying the neuroprotective effects of antidepressants in the treatment of MDD.