Comparing the Effect of Fluoxetine, Escitalopram, and Sertraline, on the Level of BDNF and Depression in Preclinical and Clinical Studies: a Systematic Review

Overview

Journal Eur J Clin Pharmacol

Specialty Pharmacology

Date 2024 Apr 1

PMID 38558317

Authors

Nastaran Talaee

Shataw Azadvar

Sanaz Khodadadi

Nahal Abbasi

Zahra Najafi Asli-Pashaki

Yasaman Mirabzadeh

Gita Kholghi

Shahin Akhondzadeh

Salar Vaseghi

Affiliations

Soon will be listed here.

Abstract

Brain-derived neurotrophic factor (BDNF) dysfunction is one of the most important mechanisms underlying depression. It seems that selective serotonin reuptake inhibitors (SSRIs) improve depression via affecting BDNF level. In this systematic review, for the first time, we aimed to review the effect of three SSRIs including fluoxetine, escitalopram, and sertraline, on both depression and BDNF level in preclinical and clinical studies. PubMed electronic database was searched, and 193 articles were included in this study. After reviewing all manuscripts, only one important difference was found: subjects. We found that SSRIs induce different effects in animals vs. humans. Preclinical studies showed many controversial effects, while human studies showed only two effects: improvement of depression, with or without the improvement of BDNF. However, most studies used chronic SSRIs treatment, while acute SSRIs were not effectively used and evaluated. In conclusion, it seems that SSRIs are reliable antidepressants, and the improvement effect of SSRIs on depression is not dependent to BDNF level (at least in human studies).

Citing Articles

Efficacy, safety and mechanistic insights of pentoxifylline in major depressive disorder: a systematic review and meta-analysis of randomized controlled trials.

Kassar O, Farag N, Selim A, Taman L, Alaa M, Elshahat A Naunyn Schmiedebergs Arch Pharmacol. 2025; .

PMID: 39985579 DOI: 10.1007/s00210-025-03845-1.

Brain-derived neurotrophic factor (BDNF) changes in rodent models of schizophrenia induced by ketamine: a systematic review.

Motamedi-Manesh A, Asanjan M, Fallah H, Gharibian S, Taghavi A, Poode Z Naunyn Schmiedebergs Arch Pharmacol. 2025; .

PMID: 39976721 DOI: 10.1007/s00210-025-03912-7.

Activating the Astrocytes of the Dorsal Raphe Nucleus via Its Neural Circuits With the Medial Prefrontal Cortex Improves Depression in Mice.

Zhao J, Wang Y, Tian C, Wang J, Chen F, Dong X Behav Neurol. 2025; 2025:8890705.

PMID: 39803364 PMC: 11717441. DOI: 10.1155/bn/8890705.

New Insights into Contradictory Changes in Brain-Derived Neurotrophic Factor (BDNF) in Rodent Models of Posttraumatic Stress Disorder (PTSD).

Ghaffarzadegan R, Akhondzadeh S, Nikasa Z, Hajizamani S, Mehrabanifar S, Cheraghi I Neurochem Res. 2024; 49(12):3226-3243.

PMID: 39283581 DOI: 10.1007/s11064-024-04242-5.

The multifaceted effects of fluoxetine treatment on cognitive functions.

Ampuero E, Luarte A, Flores F, Soto A, Pino C, Silva V Front Pharmacol. 2024; 15:1412420.

PMID: 39081952 PMC: 11286485. DOI: 10.3389/fphar.2024.1412420.

References

Malhi G, Mann J . Depression. Lancet. 2018; 392(10161):2299-2312. DOI: 10.1016/S0140-6736(18)31948-2. View

Tang Y, Wang H, Nie K, Gao Y, Su H, Wang Z . Traditional herbal formula Jiao-tai-wan improves chronic restrain stress-induced depression-like behaviors in mice. Biomed Pharmacother. 2022; 153:113284. DOI: 10.1016/j.biopha.2022.113284. View

Zhou Z, Chen H, Tang X, He B, Gu L, Feng H . Total Saikosaponins Attenuates Depression-Like Behaviors Induced by Chronic Unpredictable Mild Stress in Rats by Regulating the PI3K/AKT/NF-B Signaling Axis. Evid Based Complement Alternat Med. 2022; 2022:4950414. PMC: 9233589. DOI: 10.1155/2022/4950414. View

Shin J, Lee J, Choi J, Ahn B, Jang S, You S . Rapid-Onset Antidepressant-Like Effect of in Social Hierarchy Stress Model of Depression. Evid Based Complement Alternat Med. 2022; 2022:6897359. PMC: 9168086. DOI: 10.1155/2022/6897359. View

Baxter A, Scott K, Ferrari A, Norman R, Vos T, Whiteford H . Challenging the myth of an "epidemic" of common mental disorders: trends in the global prevalence of anxiety and depression between 1990 and 2010. Depress Anxiety. 2014; 31(6):506-16. DOI: 10.1002/da.22230. View

Leonard B . Inflammation and depression: a causal or coincidental link to the pathophysiology?. Acta Neuropsychiatr. 2017; 30(1):1-16. DOI: 10.1017/neu.2016.69. View

Dantzer R . Role of the Kynurenine Metabolism Pathway in Inflammation-Induced Depression: Preclinical Approaches. Curr Top Behav Neurosci. 2016; 31:117-138. PMC: 6585430. DOI: 10.1007/7854_2016_6. View

Haroon E, Miller A . Inflammation Effects on Brain Glutamate in Depression: Mechanistic Considerations and Treatment Implications. Curr Top Behav Neurosci. 2016; 31:173-198. DOI: 10.1007/7854_2016_40. View

Phillips C . Brain-Derived Neurotrophic Factor, Depression, and Physical Activity: Making the Neuroplastic Connection. Neural Plast. 2017; 2017:7260130. PMC: 5591905. DOI: 10.1155/2017/7260130. View

10.

Ebrahimnejad M, Azizi P, Alipour V, Zarrindast M, Vaseghi S . Complicated Role of Exercise in Modulating Memory: A Discussion of the Mechanisms Involved. Neurochem Res. 2022; 47(6):1477-1490. DOI: 10.1007/s11064-022-03552-w. View

11.

Dwivedi Y . Brain-derived neurotrophic factor: role in depression and suicide. Neuropsychiatr Dis Treat. 2009; 5:433-49. PMC: 2732010. DOI: 10.2147/ndt.s5700. View

12.

Mendez-David I, Guilloux J, Papp M, Tritschler L, Mocaer E, Gardier A . S 47445 Produces Antidepressant- and Anxiolytic-Like Effects through Neurogenesis Dependent and Independent Mechanisms. Front Pharmacol. 2017; 8:462. PMC: 5515821. DOI: 10.3389/fphar.2017.00462. View

13.

Duman R, Monteggia L . A neurotrophic model for stress-related mood disorders. Biol Psychiatry. 2006; 59(12):1116-27. DOI: 10.1016/j.biopsych.2006.02.013. View

14.

Autry A, Monteggia L . Brain-derived neurotrophic factor and neuropsychiatric disorders. Pharmacol Rev. 2012; 64(2):238-58. PMC: 3310485. DOI: 10.1124/pr.111.005108. View

15.

Russo-Neustadt A, Beard R, Cotman C . Exercise, antidepressant medications, and enhanced brain derived neurotrophic factor expression. Neuropsychopharmacology. 1999; 21(5):679-82. DOI: 10.1016/S0893-133X(99)00059-7. View

16.

Wang D, Li T, Han X, He W, Yan Y . Xingnao Jieyu Decoction Reduces Neuroinflammation through the NF-B Pathway to Improve Poststroke Depression. Evid Based Complement Alternat Med. 2021; 2021:8629714. PMC: 8557073. DOI: 10.1155/2021/8629714. View

17.

Serebruany V, Suckow R, Cooper T, OConnor C, Malinin A, Krishnan K . Relationship between release of platelet/endothelial biomarkers and plasma levels of sertraline and N-desmethylsertraline in acute coronary syndrome patients receiving SSRI treatment for depression. Am J Psychiatry. 2005; 162(6):1165-70. DOI: 10.1176/appi.ajp.162.6.1165. View

18.

DeLucia V, Kelsberg G, Safranek S . Which SSRIs most effectively treat depression in adolescents?. J Fam Pract. 2016; 65(9):632-4. View

19.

Vermetten E, Vythilingam M, Schmahl C, de Kloet C, Southwick S, Charney D . Alterations in stress reactivity after long-term treatment with paroxetine in women with posttraumatic stress disorder. Ann N Y Acad Sci. 2006; 1071:184-202. PMC: 3230329. DOI: 10.1196/annals.1364.014. View

20.

Edinoff A, Akuly H, Hanna T, Ochoa C, Patti S, Ghaffar Y . Selective Serotonin Reuptake Inhibitors and Adverse Effects: A Narrative Review. Neurol Int. 2021; 13(3):387-401. PMC: 8395812. DOI: 10.3390/neurolint13030038. View