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Transcranial Direct Current Stimulation for the Treatment of Depression: a Comprehensive Review of the Recent Advances

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Abstract

Preclinical and clinical studies have shown promising therapeutic effects of tDCS for treatment of depressive disorders (DDs). However, the clinical applications of the technique are in still in the initial phase. This paper aims to review the therapeutic applications of tDCS for the treatment of DDs, to discuss its safety, and current clinical challenges of the technique. The databases of PubMed (1985–2016), EMBASE (1980–2016), Web of Sciences (1980–2016), and Google Scholar (1980–2016) were searched using the search terms “transcranial direct current stimulation” or “tDCS”, “depressive disorder” or “DD”, “depression”, “safety”, “clinical application”, and “treatment”. Current evidence shows tDCS is effective in reducing depressive symptoms. In addition to the potential clinical utility and minimal adverse-effects of tDCS, it appears to improve cognitive performance. Furthermore, the interesting clinical importance of tDCS is its therapeutic efficacy for both treatment-resistant and non-treatment-resistant patients with mild to moderate depression. tDCS has been reportedly associated with no serious adverse effects with the most frequent adverse effects being headaches, itchiness, and redness at the site of stimulation.

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References

  • Aarre, T. F., Dahl, A. A., Johansen, J. B., Kjønniksen, I., & Neckelmann, D. (2003). Efficacy of repetitive transcranial magnetic stimulation in depression: a review of the evidence. Nordic Journal of Psychiatry, 57(3), 227–232.

    Article  PubMed  Google Scholar 

  • Ali, Y., Mahmud, N. A., & Samaneh, R. (2015). Current advances in neurofeedback techniques for the treatment of ADHD. Biomedical and Pharmacology Journal, 8, 165–177. doi:10.13005/bpj/573.

    Article  Google Scholar 

  • Antal, A., Kincses, T. Z., Nitsche, M. A., Bartfai, O., & Paulus, W. (2004). Excitability changes induced in the human primary visual cortex by transcranial direct current stimulation: direct electrophysiological evidence. Investigative Ophthalmology & Visual Science, 45(2), 702–707.

    Article  Google Scholar 

  • Arfai, E., Theano, G., Montagu, J., & Robin, A. (1970). A controlled study of polarization in depression. The British Journal of Psychiatry, 116(533), 433–434.

    Article  CAS  PubMed  Google Scholar 

  • Arul-Anandam, A. P., & Loo, C. (2009). Transcranial direct current stimulation: a new tool for the treatment of depression? Journal of Affective Disorders, 117(3), 137–145.

    Article  PubMed  Google Scholar 

  • Baker, A. (1970). Brain stem polarization in the treatment of depression. South African Medical Journal = Suid-Afrikaanse tydskrif vir geneeskunde, 44(16), 473–475.

    CAS  PubMed  Google Scholar 

  • Bell, I. R., Schwartz, G. E., Hardin, E. E., Baldwin, C. M., & Kline, J. P. (1998). Differential resting quantitative electroencephalographic alpha patterns in women with environmental chemical intolerance, depressives, and normals. Biological Psychiatry, 43(5), 376–388.

    Article  CAS  PubMed  Google Scholar 

  • Bindman, L. J., Lippold, O., & Redfearn, J. (1964). The action of brief polarizing currents on the cerebral cortex of the rat (1) during current flow and (2) in the production of long-lasting after-effects. The Journal of Physiology, 172(3), 369.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Boggio, P. S., Bermpohl, F., Vergara, A. O., Muniz, A. L., Nahas, F. H., Leme, P. B., et al. (2007). Go-no-go task performance improvement after anodal transcranial DC stimulation of the left dorsolateral prefrontal cortex in major depression. Journal of Affective Disorders, 101(1), 91–98.

    Article  PubMed  Google Scholar 

  • Boggio, P. S., Rigonatti, S. P., Ribeiro, R. B., Myczkowski, M. L., Nitsche, M. A., Pascual-Leone, A., & Fregni, F. (2008). A randomized, double-blind clinical trial on the efficacy of cortical direct current stimulation for the treatment of major depression. The International Journal of Neuropsychopharmacology, 11(2), 249.

    Article  PubMed  Google Scholar 

  • Boggio, P. S., Zaghi, S., & Fregni, F. (2009). Modulation of emotions associated with images of human pain using anodal transcranial direct current stimulation (tDCS). Neuropsychologia, 47(1), 212–217.

    Article  PubMed  Google Scholar 

  • Bruder, G. E., Stewart, J. W., Mercier, M. A., Agosti, V., Leite, P., Donovan, S., & Quitkin, F. M. (1997). Outcome of cognitive–behavioral therapy for depression: relation to hemispheric dominance for verbal processing. Journal of Abnormal Psychology, 106(1), 138.

    Article  CAS  PubMed  Google Scholar 

  • Brunelin, J., Poulet, E., Boeuve, C., Zeroug-Vial, H., d'Amato, T., & Saoud, M. (2006). Efficacy of repetitive transcranial magnetic stimulation (rTMS) in major depression: a review. L'Encephale, 33(2), 126–134.

    Article  Google Scholar 

  • Brunoni, A., Ferrucci, R., Bortolomasi, M., Vergari, M., Tadini, L., Boggio, P., et al. (2011). Transcranial direct current stimulation (tDCS) in unipolar vs. bipolar depressive disorder. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 35(1), 96–101.

    Article  CAS  PubMed  Google Scholar 

  • Brunoni, A. R., Valiengo, L., Baccaro, A., Zanao, T. A., de Oliveira, J. F., Goulart, A., et al. (2013). The sertraline vs electrical current therapy for treating depression clinical study: results from a factorial, randomized, controlled trial. JAMA Psychiatry, 70(4), 383–391.

    Article  CAS  PubMed  Google Scholar 

  • Carney, M., Cashman, M., & Sheffield, B. (1970). Polarization in depression. The British Journal of Psychiatry, 117(539), 474–475.

    Article  CAS  PubMed  Google Scholar 

  • Coffey, C. E., Wilkinson, W. E., Weiner, R. D., Djang, W. T., Webb, M. C., Figiel, G. S., & Spritzer, C. E. (1993). Quantitative cerebral anatomy in depression: a controlled magnetic resonance imaging study. Archives of General Psychiatry, 50(1), 7.

    Article  CAS  PubMed  Google Scholar 

  • Cooke, R. G. (2003). Repetitive transcranial magnetic stimulation for depression. Journal of Psychiatry and Neuroscience, 28(5), 400.

    PubMed  PubMed Central  Google Scholar 

  • Costain, R., Redfearn, J., & Lippold, O. (1964). A controlled trial of the therapeutic effects of polarization of the brain in depressive illness. The British Journal of Psychiatry.

    Google Scholar 

  • Creutzfeldt, O. D., Fromm, G. H., & Kapp, H. (1962). Influence of transcortical dc currents on cortical neuronal activity. Experimental Neurology, 5(6), 436–452.

    Article  CAS  PubMed  Google Scholar 

  • Davidson, R. J., Pizzagalli, D., Nitschke, J. B., & Putnam, K. (2002). Depression: perspectives from affective neuroscience. Annual Review of Psychology, 53(1), 545–574.

    Article  PubMed  Google Scholar 

  • Debener, S., Beauducel, A., Nessler, D., Brocke, B., Heilemann, H., & Kayser, J. (2000). Is resting anterior EEG alpha asymmetry a trait marker for depression? Neuropsychobiology, 41(1), 31–37.

    Article  CAS  PubMed  Google Scholar 

  • Drevets, M., & Wayne, C. (1998). Functional neuroimaging studies of depression: the anatomy of melancholia. Annual Review of Medicine, 49(1), 341–361.

    Article  CAS  PubMed  Google Scholar 

  • Drevets, W. C., Price, J. L., Simpson, J. R., Todd, R. D., Reich, T., Vannier, M., & Raichle, M. E. (1997). Subgenual prefrontal cortex abnormalities in mood disorders.

    Google Scholar 

  • Fink, M. (2001). Convulsive therapy: a review of the first 55 years. Journal of Affective Disorders, 63(1), 1–15.

    Article  CAS  PubMed  Google Scholar 

  • Fitzgerald, P. B., Oxley, T. J., Laird, A. R., Kulkarni, J., Egan, G. F., & Daskalakis, Z. J. (2006). An analysis of functional neuroimaging studies of dorsolateral prefrontal cortical activity in depression. Psychiatry Research: Neuroimaging, 148(1), 33–45.

    Article  PubMed  Google Scholar 

  • Fregni, F., Boggio, P. S., Nitsche, M. A., Marcolin, M. A., Rigonatti, S. P., & Pascual-Leone, A. (2006). Treatment of major depression with transcranial direct current stimulation. Bipolar Disorders, 8(2), 203–204.

    Article  PubMed  Google Scholar 

  • Gartside, I. B. (1968a). Mechanisms of sustained increases of firing rate of neurons in the rat cerebral cortex after polarization: reverberating circuits or modification of synaptic conductance?. Nature, 220(5165), 382–383.

  • Gartside, I. B. (1968b). Mechanisms of sustained increases of firing rate of neurones in the rat cerebral cortex after polarization: role of protein synthesis. Nature, 220(5165), 383.

  • Gotlib, I. H. (1998). EEG alpha asymmetry, depression, and cognitive functioning. Cognition & Emotion, 12(3), 449–478.

    Article  Google Scholar 

  • Hattori, Y., Moriwaki, A., & Hori, Y. (1990). Biphasic effects of polarizing current on adenosine-sensitive generation of cyclic AMP in rat cerebral cortex. Neuroscience Letters, 116(3), 320–324.

    Article  CAS  PubMed  Google Scholar 

  • Herjanic, M., & Moss-Herjanic, B. (1967). Clinical report on a new therapeutic technique: polarization. The Canadian Psychiatric Association Journal/La Revue de l'Association des psychiatres du Canada.

  • Islam, N., Aftabuddin, M., Moriwaki, A., Hattori, Y., & Hori, Y. (1995). Increase in the calcium level following anodal polarization in the rat brain. Brain Research, 684(2), 206–208.

    Article  CAS  PubMed  Google Scholar 

  • Jalilifar, M., Yadollahpour, A., Moazedi, A. A., & Ghotbeddin, Z. (2016). Classifying amygdala kindling stages using quantitative assessments of extracellular recording of EEG in rats. Brain Research Bulletin, 127, 148–155. doi:10.1016/j.brainresbull.2016.09.012.

    Article  PubMed  Google Scholar 

  • Kennedy, S. H., Evans, K. R., Krüger, S., Mayberg, H. S., Meyer, J. H., McCann, S., … Vaccarino, F. J. (2001). Changes in regional brain glucose metabolism measured with positron emission tomography after paroxetine treatment of major depression. American Journal of Psychiatry.

  • Kentgen, L. M., Tenke, C. E., Pine, D. S., Fong, R., Klein, R. G., & Bruder, G. E. (2000). Electroencephalographic asymmetries in adolescents with major depression: influence of comorbidity with anxiety disorders. Journal of Abnormal Psychology, 109(4), 797.

    Article  CAS  PubMed  Google Scholar 

  • Koenigs, M., & Grafman, J. (2009). The functional neuroanatomy of depression: distinct roles for ventromedial and dorsolateral prefrontal cortex. Behavioural Brain Research, 201(2), 239–243.

    Article  PubMed  PubMed Central  Google Scholar 

  • Lang, N., Siebner, H. R., Ward, N. S., Lee, L., Nitsche, M. A., Paulus, W., et al. (2005). How does transcranial DC stimulation of the primary motor cortex alter regional neuronal activity in the human brain? European Journal of Neuroscience, 22(2), 495–504.

    Article  PubMed  PubMed Central  Google Scholar 

  • Lian, J., Bikson, M., Sciortino, C., Stacey, W. C., & Durand, D. M. (2003). Local suppression of epileptiform activity by electrical stimulation in rat hippocampus in vitro. The Journal of Physiology, 547(2), 427–434.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liebetanz, D., Nitsche, M. A., Tergau, F., & Paulus, W. (2002). Pharmacological approach to the mechanisms of transcranial DC-stimulation-induced after-effects of human motor cortex excitability. Brain, 125(10), 2238–2247.

    Article  PubMed  Google Scholar 

  • Liebetanz, D., Klinker, F., Hering, D., Koch, R., Nitsche, M. A., Potschka, H., et al. (2006). Anticonvulsant effects of transcranial direct-current stimulation (tDCS) in the rat cortical ramp model of focal epilepsy. Epilepsia, 47(7), 1216–1224.

    Article  PubMed  Google Scholar 

  • Lippold, O., & Redfearn, J. (1964). Mental changes resulting from the passage of small direct currents through the human brain. The British Journal of Psychiatry, 110(469), 768–772.

    Article  CAS  PubMed  Google Scholar 

  • Loo, C. K., Alonzo, A., Martin, D., Mitchell, P. B., Galvez, V., & Sachdev, P. (2012). Transcranial direct current stimulation for depression: 3-week, randomised, sham-controlled trial. The British Journal of Psychiatry, 200(1), 52–59.

    Article  PubMed  Google Scholar 

  • Löscher, W., Cole, A. J., & McLean, M. J. (2009). Commentary: physical approaches for the treatment of epilepsy: electrical and magnetic stimulation and cooling. Neurotherapeutics, 6(2), 258–262.

    Article  PubMed  PubMed Central  Google Scholar 

  • Mostafa, J., Ali, Y., Zohre, R., & Samaneh, R. (2015). Electromagnetic Fields and Ultrasound Waves in Wound Treatment: A Comparative Review of Therapeutic Outcomes. Biosciences, Biotechnology Research Asia, 12(Spl.Edn.1), 185–195.

    Article  Google Scholar 

  • Murray, C. J., & Lopez, A. D. (1996). Evidence-based health policy--lessons from the global burden of disease study. Science, 274(5288), 740.

    Article  CAS  PubMed  Google Scholar 

  • Nias, D., & Shapiro, M. (1974). The effects of small electrical currents upon depressive symptoms. The British Journal of Psychiatry.

  • Nitsche, M., & Paulus, W. (2000). Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation. The Journal of Physiology, 527(3), 633–639.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nitsche, M. A., & Paulus, W. (2001). Sustained excitability elevations induced by transcranial DC motor cortex stimulation in humans. Neurology, 57(10), 1899–1901.

    Article  CAS  PubMed  Google Scholar 

  • Nitsche, M., Fricke, K., Henschke, U., Schlitterlau, A., Liebetanz, D., Lang, N., et al. (2003a). Pharmacological modulation of cortical excitability shifts induced by transcranial direct current stimulation in humans. The Journal of Physiology, 553(1), 293–301.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nitsche, M. A., Nitsche, M. S., Klein, C. C., Tergau, F., Rothwell, J. C., & Paulus, W. (2003b). Level of action of cathodal DC polarisation induced inhibition of the human motor cortex. Clinical Neurophysiology, 114(4), 600–604.

    Article  PubMed  Google Scholar 

  • Nitsche, M. A., Grundey, J., Liebetanz, D., Lang, N., Tergau, F., & Paulus, W. (2004a). Catecholaminergic consolidation of motor cortical neuroplasticity in humans. Cerebral Cortex, 14(11), 1240–1245.

    Article  PubMed  Google Scholar 

  • Nitsche, M. A., Jaussi, W., Liebetanz, D., Lang, N., Tergau, F., & Paulus, W. (2004b). Consolidation of human motor cortical neuroplasticity by D-cycloserine. Neuropsychopharmacology, 29(8).

  • Nitsche, M. A., Lampe, C., Antal, A., Liebetanz, D., Lang, N., Tergau, F., & Paulus, W. (2006). Dopaminergic modulation of long-lasting direct current-induced cortical excitability changes in the human motor cortex. European Journal of Neuroscience, 23(6), 1651–1657.

    Article  PubMed  Google Scholar 

  • Nitsche, M. A., Boggio, P. S., Fregni, F., & Pascual-Leone, A. (2009). Treatment of depression with transcranial direct current stimulation (tDCS): a review. Experimental Neurology, 219(1), 14–19.

    Article  PubMed  Google Scholar 

  • Pauli, P., Wiedemann, G., & Nickola, M. (1999). Pain sensitivity, cerebral laterality, and negative affect. Pain, 80(1), 359–364.

    Article  CAS  PubMed  Google Scholar 

  • Paulus, W. (2003). Outlasting excitability shifts induced by direct current stimulation of the human brain. Supplements to Clinical Neurophysiology, 57, 708–714.

    Article  Google Scholar 

  • Powell, T. Y., Boonstra, T. W., Martin, D. M., Loo, C. K., & Breakspear, M. (2014). Modulation of cortical activity by transcranial direct current stimulation in patients with affective disorder. PloS One, 9(6), e98503.

    Article  PubMed  PubMed Central  Google Scholar 

  • Purpura, D. P., & McMurtry, J. G. (1965). Intracellular activities and evoked potential changes during polarization of motor cortex. Journal of Neurophysiology, 28(1), 166–185.

    CAS  PubMed  Google Scholar 

  • Rajkowska, G. (2000). Postmortem studies in mood disorders indicate altered numbers of neurons and glial cells. Biological psychiatry, 48(8), 766--777.

  • Ramsay, J., & Schlagenhauf, G. (1966). Treatment of depression with low voltage direct current. Southern Medical Journal, 59(8), 932–934.

    Article  CAS  PubMed  Google Scholar 

  • Rashidi, S., Yadollahpour, A., & Mirzaiyan, M. (2015a). Low level laser therapy for the treatment of chronic wound: clinical considerations. Biomedical and Pharmacology Journal, 8(2), 1121–1127.

    Article  Google Scholar 

  • Rashidi, S., Yadollahpour, A., Jalilifar, M., Naraqi arani, M., & Rezaee, Z. (2015b). Laser Therapy for Wound Healing: A Review of Current Techniques and Mechanisms of Action. Biosciences, Biotechnology Research Asia, 12(Spl.Edn.1), 217–223.

    Google Scholar 

  • Reid, S. A., Duke, L. M., & Allen, J. J. (1998). Resting frontal electroencephalographic asymmetry in depression: inconsistencies suggest the need to identify mediating factors. Psychophysiology, 35(4), 389–404.

    Article  CAS  PubMed  Google Scholar 

  • Rezaee, Z., Yadollahpour, A., Jalilifar, M., & Rashidi, S. (2015). Nondrug Antimicrobial Techniques: Electromagnetic Fields and Photodynamic Therapy. Biomedical & Pharmacology Journal, 8 , 147–155.March Spl Edition

    Article  Google Scholar 

  • Rigonatti, S. P., Boggio, P. S., Myczkowski, M. L., Otta, E., Fiquer, J. T., Ribeiro, R. B., et al. (2008). Transcranial direct stimulation and fluoxetine for the treatment of depression. European Psychiatry, 23(1), 74–76.

    Article  PubMed  Google Scholar 

  • Sackeim, H. A., Rush, A. J., George, M. S., Marangell, L. B., Husain, M. M., Nahas, Z., et al. (2001). Vagus nerve stimulation (VNS™) for treatment-resistant depression: efficacy, side effects, and predictors of outcome. Neuropsychopharmacology, 25(5), 713–728.

    Article  CAS  PubMed  Google Scholar 

  • Sadeghi, K., & Khazaie, H. (2013). The comparison of efficacy pharmacotherapy and group cognitive therapy in dimensions of temperament and character of patients with major depression disorder. Journal of Kermanshah University of Medical Sciences (J Kermanshah Univ Med Sci), 17(4), 230–236.

    Google Scholar 

  • Shiozawa, P., Fregni, F., Benseñor, I. M., Lotufo, P. A., Berlim, M. T., Daskalakis, J. Z., et al. (2014). Transcranial direct current stimulation for major depression: an updated systematic review and meta-analysis. The International Journal of Neuropsychopharmacology, 17(09), 1443–1452.

    Article  PubMed  Google Scholar 

  • Talebi, M., & Fathi-Ashtiani, A. (2015). The effectiveness of transcranial direct current stimulation of the brain (tDCS) on reducing depressive symptoms among people with depressive disorder. International Journal of Behavioral Sciences, 9(1), 95–101.

    Google Scholar 

  • Wachter, D., Wrede, A., Schulz-Schaeffer, W., Taghizadeh-Waghefi, A., Nitsche, M. A., Kutschenko, A., et al. (2011). Transcranial direct current stimulation induces polarity-specific changes of cortical blood perfusion in the rat. Experimental Neurology, 227(2), 322–327.

    Article  PubMed  Google Scholar 

  • Yadollahpour, A., & Jalilifar, M. (2014a). Electromagnetic fields in the treatment of wound: a review of current techniques and future perspective. Journal of Pure and Applied Microbiology, 8(4), 2863–2877.

    Google Scholar 

  • Yadollahpour, A., & Jalilifar, M. (2014b). Seizure prediction methods: A review of the current predicting techniques. Biomedical and Pharmacology Journal, 7(1), 153–162. doi:10.13005/bpj/466.

    Article  Google Scholar 

  • Yadollahpour, A., & Rashidi, S. (2014a). A review of electromagnetic field based treatments for different bone fractures. Biosciences, Biotechnology Research Asia, 11(2), 611–620.

    Article  Google Scholar 

  • Yadollahpour, A., & Rashidi, S. (2014b). Therapeutic applications of electromagnetic fields in musculoskeletal disorders: a review of current techniques and mechanisms of action. Biomedical and Pharmacology Journal, 7(1), 23–32.

    Article  CAS  Google Scholar 

  • Yadollahpour, A., Jalilifar, M., & Rashidi, S. (2014a). Antimicrobial effects of electromagnetic fields: a review of current techniques and mechanisms of action. Journal of Pure and Applied Microbiology, 8(5), 4031–4043.

    Google Scholar 

  • Yadollahpour, A., Mostafa, J., Samaneh, R., & Zohreh, R. (2014b). Ultrasound therapy for wound healing: a review of current techniques and mechanisms of action. Journal of Pure and Applied Microbiology, 8(5), 4071–4085.

    Google Scholar 

  • Yang, Y., & Raine, A. (2009). Prefrontal structural and functional brain imaging findings in antisocial, violent, and psychopathic individuals: a meta-analysis. Psychiatry Research: Neuroimaging, 174(2), 81–88.

    Article  PubMed  PubMed Central  Google Scholar 

  • Zaehle, T., Sandmann, P., Thorne, J. D., Jäncke, L., & Herrmann, C. S. (2011). Transcranial direct current stimulation of the prefrontal cortex modulates working memory performance: combined behavioural and electrophysiological evidence. BMC Neuroscience, 12(1), 1.

    Article  Google Scholar 

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Yadollahpour, A., Jalilifar, M. & Rashidi, S. Transcranial Direct Current Stimulation for the Treatment of Depression: a Comprehensive Review of the Recent Advances. Int J Ment Health Addiction 15, 434–443 (2017). https://doi.org/10.1007/s11469-017-9741-3

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