Cytokines plasma levels during antidepressant treatment with sertraline and transcranial direct current stimulation (tDCS): results from a factorial, randomized, controlled trial
- 618 Downloads
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.
We explored the effects of tDCS and sertraline over the immune system during an antidepressant treatment trial.
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.
All cytokines, except TNF-α, decreased over time, these effects being similar across the different intervention-groups and in responders vs. non-responders.
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.
KeywordsMajor depressive disorder Transcranial direct current stimulation Sertraline Cytokines Interleukins Randomized Controlled trial Placebo response Placebo effect
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.
Conflict of interest
- Brunoni AR, Ferrucci R, Bortolomasi M, Scelzo E, Boggio PS, Fregni F, Dell'Osso B, Giacopuzzi M, Altamura AC, Priori A (2012a) Interactions between transcranial direct current stimulation (tDCS) and pharmacological interventions in the major depressive episode: findings from a naturalistic study. Eur Psychiatry 28(6):356–361CrossRefGoogle Scholar
- Brunoni AR, Kemp AH, Dantas EM, Goulart AC, Nunes MA, Boggio PS, Mill JG, Lotufo PA, Fregni F, Benseñor IM (2013a) Heart rate variability is a trait marker of major depressive disorder: evidence from the sertraline vs. electric current therapy to treat depression clinical study. Int J Neuropsychopharmacol 16(9):1937–1949CrossRefGoogle Scholar
- Brunoni AR, Nitsche MA, Bolognini N, Bikson M, Wagner T, Merabet L, Edwards DJ, Valero-Cabre A, Rotenberg A, Pascual-Leone A, Ferrucci R, Priori A, Boggio PS, Fregni F (2012b) Clinical research with transcranial direct current stimulation (tDCS): challenges and future directions. Brain Stimul 5:175–95PubMedCentralPubMedCrossRefGoogle Scholar
- Brunoni AR, Valiengo L, Baccaro A, Zanao TA, de Oliveira JF, Vieira GP, Bueno VF, Goulart AC, Boggio PS, Lotufo PA, Bensenor IM, Fregni F (2011b) Sertraline vs. Electrical Current Therapy for Treating Depression Clinical Trial–SELECT TDCS: design, rationale and objectives. Contemp Clin Trials 32:90–8PubMedCrossRefGoogle Scholar
- Brunoni AR, Valiengo L, Baccaro A, Zanao TA, Oliveira AC, Goulart AC, Boggio PS, Lotufo PA, Bensenor IJ, Fregni F (2013b) The Sertraline versus Electrical Current Therapy for Treating Depression Clinical Study: results from a factorial, randomized, controlled trial. JAMA Psychiatry 70:383–91PubMedCrossRefGoogle Scholar
- Brunoni AR, Vanderhasselt MA, Boggio PS, Fregni F, Dantas EM, Mill JG, Lotufo PA, Bensenor IJ (2013c) Polarity- and valence-dependent effects of prefrontal transcranial direct current stimulation on heart rate variability and salivary cortisol. Psychoneuroendocrinology 38:58–66PubMedCrossRefGoogle Scholar
- Fidalgo TM, Morales-Quezada JL, Muzy GS, Chiavetta NM, Mendonca ME, Santana MV, Goncalves OF, Brunoni AR, Fregni F (2013) Biological markers in noninvasive brain stimulation trials in major depressive disorder: a systematic review. J ECT. In press.Google Scholar
- Fruscella P, Sottocorno M, Di Braccio M, Diomede L, Piccardi N, Cagnotto A, Grossi G, Romano M, Mennini T, Roma G (2001) 1,5-Benzodiazepine tricyclic derivatives exerting anti-inflammatory effects in mice by inhibiting interleukin-6 and prostaglandin E(2) production. Pharmacol Res: Off J Ital Pharmacol Soc 43:445–52CrossRefGoogle Scholar
- Gorenstein C, Andrade LHSG, Zuardi AW (2000) Escalas de Avaliação Clínica em Psiquiatria e Psicofarmacologia, Sao PauloGoogle Scholar
- Taupin V, Gogusev J, Descamps-Latscha B, Zavala F (1993) Modulation of tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, interleukin-8, and granulocyte/macrophage colony-stimulating factor expression in human monocytes by an endogenous anxiogenic benzodiazepine ligand, triakontatetraneuropeptide: evidence for a role of prostaglandins. Mol Pharmacol 43:64–9PubMedGoogle Scholar