Oxidative damage and major depression: the potential antioxidant action of selective serotonin re-uptake inhibitors

Khanzode, Suchet D.; Dakhale, Ganesh N.; Khanzode, Shruti S.; Saoji, Anand; Palasodkar, R.

doi:10.1179/135100003225003393

Cited by 458Treatment of Major DepressionAntioxidant Activity and Oxidative StressTryptophan and brain disorders

Oxidative damage and major depression: the potential antioxidant action of selective serotonin re-uptake inhibitors

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Khanzode, Suchet D., Dakhale, Ganesh N., Khanzode, Shruti S., Saoji, Anand, Palasodkar, R.·2003·Redox Report

DOI 10.1179/135100003225003393

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Abstract

There is evidence of derangement of oxidant and antioxidant defense systems in depression. The present study examined the effects of fluoxetine and citalopram, standard selective serotonin re-uptake inhibitors, on lipid peroxidation, superoxide dismutase (SOD) activity and ascorbic acid concentrations. For this, a prospective open-labeled, randomized design was utilized. Patients with major depression (n = 62) were compared with age- and sex-matched healthy volunteers (n = 40). There was a significant increase in serum SOD, serum MDA and decrease in plasma ascorbic acid levels in patients of major depression as compared to control subjects. The trend reversed significantly after treatment with fluoxetine and citalopram. Results indicate a greater reduction in oxidative stress with citalopram than fluoxetine. The Hamilton Rating Scale for Depression (HRSD) score also improved with fluoxetine and citalopram treatment. These findings indicate that major depression is associated with increased levels of serum SOD, serum MDA and decreased levels of plasma ascorbic acid. Treatment with fluoxetine and citalopram reversed these biochemical parameters. This study can be used as a predictor of drug response by fluoxetine and citalopram in major depression.

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Khanzode and colleagues reported that SSRIs reduced serum levels of malondialdehyde and increased plasma ascorbic acid levels, which correlated with improvements on the Hamilton Depression Rating Scale.
“Khanzode and colleagues reported that SSRIs reduced serum levels of malondialdehyde and increased plasma ascorbic acid levels, which correlated with improvements on the Hamilton Depression Rating Scale (107).”
From Chronic stress, neuroinflammation, and depression: an overview of pathophysiological mechanisms and emerging anti-inflammatories (2023) · cites this paper as [107]
The Results report that fluoxetine and citalopram lowered serum MDA and raised plasma ascorbic acid, while Hamilton Rating Scale scores improved after 12 weeks (Results, p. 367; Tables 3, 4 and 6). They do not report a correlation between either biochemical change and improvement in the rating-scale score; the correlations listed in Results concern age or other biochemical measures. (LLM, conf=0.87)
Experimental — accuracy not yet measured
SOD activity was reported to be significantly increased in most studies of major depressive disorder.
“or a significant increase in most of the studies [123, 124, 128, 129].”
From Oxidative Stress Implications in the Affective Disorders: Main Biomarkers, Animal Models Relevance, Genetic Perspectives, and Antioxidant Approaches (2016) · cites this paper as [128]
Plasmatic vitC levels are reduced in patients with MDD compared with age- and sex-matched healthy volunteers (n = 40).
“In another study, plasmatic vitC levels were reduced in patients with MDD compared with age- and sex-matched healthy volunteers (n = 40).”
From Preclinical and Clinical Evidence of Antioxidant Effects of Antidepressant Agents: Implications for the Pathophysiology of Major Depressive Disorder (2012) · cites this paper as [27]
Oxidative stress markers (SOD, vitC, lipid peroxidation) are reversed after 4 weeks of treatment with fluoxetine (20 mg/day, n = 32) and citalopram (20 mg/day, n = 30).
“Oxidative stress markers (SOD, vitC, lipid peroxidation) were reversed after 4 weeks of treatment with fluoxetine (20 mg/day, n = 32) and citalopram (20 mg/day, n = 30).”
From Preclinical and Clinical Evidence of Antioxidant Effects of Antidepressant Agents: Implications for the Pathophysiology of Major Depressive Disorder (2012) · cites this paper as [27]
These antioxidant effects are persistent after 12 weeks of treatment.
“Notably, these antioxidant effects were persistent after 12 weeks of treatment [27].”
From Preclinical and Clinical Evidence of Antioxidant Effects of Antidepressant Agents: Implications for the Pathophysiology of Major Depressive Disorder (2012) · cites this paper as [27]

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“In fact, in MDD, while most of the authors have generally described decreased levels of GPX and increased levels of malondialdehyde (MDA), as a lipid peroxidation marker [123, 126], there are also controversies regarding the specific activity of some antioxidant enzymes such as SOD,whichwas reported to be decreased in…”
Result
Major Differences in Neurooxidative and Neuronitrosative Stress Pathways Between Major Depressive Disorder and Types I and II Bipolar Disorder
Maes, M., Landucci Bonifacio, K., Morelli, N. R., Vargas, H. O., Barbosa, D. S., Carvalho, A. F., & Nunes, S. O. V. (2019) · Molecular Neurobiology · doi:10.1007/s12035-018-1051-7 · Cited by 102 · see citing works
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Efficacy of vitamin C as an adjunct to fluoxetine therapy in pediatric major depressive disorder: a randomized, double-blind, placebo-controlled pilot study
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Clinical correlation of alteration of endogenous antioxidant-uric acid level in major depressive disorder
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Self-citation
The Effects of Escitalopram Treatment on Oxidative/ Antioxidative Parameters in Patients with Depression
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Determination of oxidative stress parameters in fluoxetine users
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Antioxidative enzyme activities and lipid peroxidation in major depression: alterations by antidepressant treatments
Bilici, M., Efe, H., Köroğlu, M. A., Uydu, H. A., Bekaroğlu, M., & Değer, O. (2001) · Journal of Affective Disorders · doi:10.1016/s0165-0327(00)00199-3 · Cited by 718 · see citing works

Authors: Khanzode, S. D., Dakhale, G. N., Khanzode, S. S., Saoji, A., & Palasodkar, R.
Affiliations: Government Medical College (IN)
ORCID: Dakhale, Ganesh N.
Venue: Redox Report
Publisher: Informa UK Limited
Published: 2003-12
Volume: 8
Issue: 6
Pages: 365-370
ISSN: 1351-0002 (ISSN-L)
1743-2928
DOI: 10.1179/135100003225003393
OpenAlex: W2090999800
Cited by: 458
References: 27
Citations by year: 2026: 11 · 2025: 17 · 2024: 24 · 2023: 14 · 2022: 27 · 2021: 19 · 2020: 24 · 2019: 25 · 2018: 29 · 2017: 23 · 2016: 25 · 2015: 29 · 2014: 35 · 2013: 29 · 2012: 30
FWCI: 3.00
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Redox Report (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Keywords: major depressive disorder, oxidative stress, selective serotonin reuptake inhibitors, fluoxetine, citalopram, lipid peroxidation, malondialdehyde, superoxide dismutase, vitamin C, antioxidant defense, antidepressant response prediction
MeSH terms: Adult, Antioxidants, Ascorbic Acid, Depression, Female, Fluoxetine, Humans, Male, Malondialdehyde, Middle Aged, Prospective Studies, Superoxide Dismutase, Time Factors, Lipid Peroxidation, Citalopram, Selective Serotonin Reuptake Inhibitors, Oxidative Stress

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Oxidative damage and major depression: the potential antioxidant action of selective serotonin re-uptake inhibitors

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