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Cytokines plasma levels during antidepressant treatment with sertraline and transcranial direct current stimulation (tDCS): results from a factorial, randomized, controlled trial

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Abstract

Rationale

The inflammatory hypothesis of depression states that increased levels of pro-inflammatory cytokines triggered by external and internal stressors are correlated to the acute depressive state. This hypothesis also suggests that pharmacotherapy partly acts in depression through anti-inflammatory effects. Transcranial direct current stimulation (tDCS) is a novel, promising, non-invasive somatic treatment for depression, although its antidepressant mechanisms are only partly understood.

Objectives

We explored the effects of tDCS and sertraline over the immune system during an antidepressant treatment trial.

Methods

In a 6-week, double-blind, placebo-controlled trial, 73 antidepressant-free patients with unipolar depression were randomized to active/sham tDCS and sertraline/placebo (2 × 2 design). Plasma levels of several cytokines (IL-2, IL-4, IL-6, IL-10, IL-17a, IFN-γ, and TNF-α) were determined to investigate the effects of the interventions and of clinical response on them.

Results

All cytokines, except TNF-α, decreased over time, these effects being similar across the different intervention-groups and in responders vs. non-responders.

Conclusions

tDCS and sertraline (separately and combined) acute antidepressant effects might not specifically involve normalization of the immune system. In addition, being one of the first placebo-controlled trials measuring cytokines over an antidepressant treatment course, our study showed that the decrease in cytokine levels during the acute depressive episode could involve a placebo effect, highlighting the need of further placebo-controlled trials and observational studies examining cytokine changes during depression treatment and also after remission of the acute depressive episode.

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Acknowledgments

This study was partially funded by FAPESP (São Paulo Research Foundation, Grant number: 2009/05728-7), FAPEMIG and CNPq. ARB receives a research grant from FAPESP (2012/20911-5) and is recipient of a 2013 NARSAD Young Investigator Award. The sponsors played no role in the design and conduct of the study, collection, management, analysis and interpretation of the data, and preparation, review or approval of the manuscript.

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Authors and Affiliations

  1. Center for Clinical and Epidemiological Research and Interdisciplinary Center for Applied Neuromodulation (CINA), University Hospital, University of São Paulo, Av. Prof Lineu Prestes 2565, 3o andar, CEP 05508-000, São Paulo, São Paulo, Brazil

    André R. Brunoni, Leandro Valiengo, Isabela M Benseñor & Paulo A. Lotufo

  2. Laboratory of Neuroscience (LIM27), Department and Institute of Psychiatry, University of São Paulo, São Paulo, Brazil

    Rodrigo Machado-Vieira, Leandro Valiengo & Wagner F. Gattaz

  3. Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health (NIMH), NIH, Bethesda, MD, USA

    Rodrigo Machado-Vieira & Carlos A. Zarate

  4. Interdisciplinary Laboratory of Medical Investigation, Faculty of Medicine of Minas Gerais, Belo Horizonte, Brazil

    Erica LM Vieira & Antonio L Teixeira

  5. Service of Interdisciplinary Neuromodulation (SIN), Department and Institute of Psychiatry, University of São Paulo, São Paulo, Brazil

    André R. Brunoni & Leandro Valiengo

Authors
  1. André R. Brunoni
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  2. Rodrigo Machado-Vieira
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  3. Carlos A. Zarate
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  4. Leandro Valiengo
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  5. Erica LM Vieira
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  6. Isabela M Benseñor
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  7. Paulo A. Lotufo
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  8. Wagner F. Gattaz
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  9. Antonio L Teixeira
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Correspondence to André R. Brunoni.

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Brunoni, A.R., Machado-Vieira, R., Zarate, C.A. et al. Cytokines plasma levels during antidepressant treatment with sertraline and transcranial direct current stimulation (tDCS): results from a factorial, randomized, controlled trial. Psychopharmacology 231, 1315–1323 (2014). https://doi.org/10.1007/s00213-013-3322-3

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  • DOI: https://doi.org/10.1007/s00213-013-3322-3

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