Molecular Neurobiology

, Volume 55, Issue 5, pp 4195–4206 | Cite as

Peripheral Alterations in Cytokine and Chemokine Levels After Antidepressant Drug Treatment for Major Depressive Disorder: Systematic Review and Meta-Analysis

  • Cristiano A. Köhler
  • Thiago H. Freitas
  • Brendon Stubbs
  • Michael Maes
  • Marco Solmi
  • Nicola Veronese
  • Nayanna Q. de Andrade
  • Gerwyn Morris
  • Brisa S. Fernandes
  • André R. Brunoni
  • Nathan Herrmann
  • Charles L. Raison
  • Brian J. Miller
  • Krista L. Lanctôt
  • André F. Carvalho


Mounting evidence suggests that aberrations in immune-inflammatory pathways contribute to the pathophysiology of major depressive disorder (MDD), and individuals with MDD may have elevated levels of predominantly pro-inflammatory cytokines and C-reactive protein. In addition, previous meta-analyses suggest that antidepressant drug treatment may decrease peripheral levels of interleukin-1 beta (IL-1β) and IL-6. Recently, several new studies examining the effect of antidepressants on these cytokines have been published, and so we performed an updated meta-analysis of studies that measured peripheral levels of cytokines and chemokines during antidepressant treatment in patients with MDD. The PubMed/MEDLINE, EMBASE, and PsycInfo databases were searched from inception through March 9, 2017. Forty-five studies met inclusion criteria (N = 1517). Peripheral levels of IL-6, tumor necrosis factor-alpha (TNF-α), IL-1β, IL-10, IL-2, IL-4, interferon-γ, IL-8, the C-C motif ligand 2 chemokine (CCL-2), CCL-3, IL-1 receptor antagonist, IL-13, IL-17, IL-5, IL-7, and the soluble IL-2 receptor were measured in at least three datasets and thus were meta-analyzed. Antidepressant treatment significantly decreased peripheral levels of IL-6 (Hedges g = −0.454, P <0.001), TNF-α (g = −0.202, P = 0.015), IL-10 (g = −0.566, P = 0.012), and CCL-2 (g = −1.502, P = 0.006). These findings indicate that antidepressants decrease several markers of peripheral inflammation. However, this meta-analysis did not provide evidence that reductions in peripheral inflammation are associated with antidepressant treatment response although few studies provided separate data for treatment responders and non-responders.


Depression Meta-analysis Antidepressant Cytokines Chemokines Inflammation 



CAK is supported by a postdoctoral fellowship award from the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, Brazil). MM is supported by a visiting research fellowship from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq; Brazil). AFC is supported by a research fellowship award from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq; Brazil).

Compliance with Ethical Standards

Conflicts of Interest

In the past 12 months, CLR has served on the scientific advisory board for Usona Institute. All other authors report no conflicts of interest.

Supplementary material

12035_2017_632_MOESM1_ESM.docx (688 kb)
ESM 1 (DOCX 688 kb)


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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Cristiano A. Köhler
    • 1
  • Thiago H. Freitas
    • 1
  • Brendon Stubbs
    • 2
    • 3
  • Michael Maes
    • 4
    • 5
    • 6
    • 7
    • 8
  • Marco Solmi
    • 9
    • 10
  • Nicola Veronese
    • 10
    • 11
  • Nayanna Q. de Andrade
    • 1
  • Gerwyn Morris
    • 4
  • Brisa S. Fernandes
    • 4
    • 12
  • André R. Brunoni
    • 13
    • 14
    • 15
  • Nathan Herrmann
    • 16
    • 17
  • Charles L. Raison
    • 18
    • 19
  • Brian J. Miller
    • 20
  • Krista L. Lanctôt
    • 16
    • 17
    • 21
  • André F. Carvalho
    • 1
    • 22
  1. 1.Translational Psychiatry Research Group and Department of Clinical Medicine, Faculty of MedicineFortalezaBrazil
  2. 2.Physiotherapy Department, South London and MaudsleyNHS Foundation TrustLondonUK
  3. 3.Health Service and Population Research Department, Institute of Psychiatry, Psychology and NeuroscienceKing’s College LondonLondonUK
  4. 4.IMPACT Strategic Research Centre, School of MedicineDeakin UniversityGeelongAustralia
  5. 5.Department of Psychiatry, Faculty of MedicineChulalongkorn UniversityBangkokThailand
  6. 6.Department of Psychiatry, Faculty of MedicineState University of LondrinaLondrinaBrazil
  7. 7.Department of PsychiatryMedical University PlovdivPlovdivBulgaria
  8. 8.RevitalisWaalreThe Netherlands
  9. 9.Department of NeurosciencesUniversity of PadovaPadovaItaly
  10. 10.Institute of Clinical Research and Education in Medicine (IREM)PaduaItaly
  11. 11.National Research Council, Neuroscience Institute, Aging BranchPadovaItaly
  12. 12.Laboratory of Calcium Binding Proteins in the Central Nervous System, Department of BiochemistryFederal University of Rio Grande do SulPorto AlegreBrazil
  13. 13.Center for Clinical and Epidemiological Research & Interdisciplinary Center for Applied Neuromodulation (CINA), University HospitalUniversity of São PauloSão PauloBrazil
  14. 14.Service of Interdisciplinary Neuromodulation (SIN), Department and Institute of PsychiatryFaculty of Medicine of University of São PauloSão PauloBrazil
  15. 15.Laboratory of Neuroscience (LIM27), Department and Institute of PsychiatryUniversity of São PauloSão PauloBrazil
  16. 16.Neuropsychopharmacology Research GroupHurvitz Brain Sciences Program Sunnybrook Research InstituteTorontoCanada
  17. 17.Department of PsychiatryUniversity of TorontoTorontoCanada
  18. 18.Department of Human Development and Family Studies, School of Human EcologyUniversity of Wisconsin-MadisonMadisonUSA
  19. 19.Department of Psychiatry, School of Medicine and Public HealthUniversity of Wisconsin-MadisonMadisonUSA
  20. 20.Department of Psychiatry & Health BehaviorGeorgia Regents UniversityAugustaUSA
  21. 21.Department of Pharmacology and ToxicologyUniversity of TorontoTorontoCanada
  22. 22.Department of Clinical Medicine, Faculty of MedicineFederal University of CearáFortalezaBrazil

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