The Impact of Transcranial Direct Current Stimulation (tDCS) on Bipolar Depression, Mania, and Euthymia: a Systematic Review of Preliminary Data

Abstract

The neurobiological basis of bipolar disorders (BD) has received increased attention and several brain regions and brain circuits have been correlated with clinical symptoms. These brain regions and circuits may represent targets for neuromodulation techniques such as transcranial Direct Current Stimulation (tDCS). We systematically reviewed the literature to explore the risks and benefits of tDCS in BD and examined all mood states. Following the PRISMA guidelines, a systematic literature search using several databases was performed from April 2002 to June 2017. From the 135 eligible studies, we retained 19 relevant articles for the systematic review, including 170 patients with BD treated by tDCS. Data from 10 studies suggest that tDCS improves depressive symptoms in BD. One case report of add-on-tDCS reported a significant positive response on manic symptoms. In 4 studies, tDCS impacted specific neurocognitive functions in euthymic patients. There is also preliminary evidence that tDCS improves neurological soft signs and sleep quality in euthymia. Side effects were predominantly transient and low-intensity, although 6 cases of hypomanic/manic affective switches have been reported. The majority of studies have been open trials with few patients. More sufficiently powered randomized controlled trials are needed to clarify the effectiveness of tDCS. Preliminary data suggests that tDCS holds promise as a treatment for BD, especially during depressive episodes. Perhaps most promising are emerging data suggesting tDCS may impact neurocognition and sleep quality in euthymia and be useful for relapse prevention.

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References

  1. 1.

    Phillips ML, Kupfer DJ. Bipolar disorder diagnosis: challenges and future directions. Lancet. 2013;381:1663–71. https://doi.org/10.1016/S0140-6736(13)60989-7.

    Article  PubMed  PubMed Central  Google Scholar 

  2. 2.

    Lefaucheur JP, André-Obadia N, Antal A, Ayache SS, Baeken C, Benninger DH, et al. Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS). Clin Neurophysiol. 2014;125:2150–206. https://doi.org/10.1016/j.clinph.2014.05.021.

    Article  PubMed  Google Scholar 

  3. 3.

    Nitsche MA, Cohen LG, Wassermann EM, Priori A, Lang N, Antal A, et al. Transcranial direct current stimulation: state of the art 2008. Brain Stimul. 2008;1(3):206–23. https://doi.org/10.1016/j.brs.2008.06.004.

    Article  PubMed  Google Scholar 

  4. 4.

    Kennedy SH, Janvanmard M, Vaccarino FJA. Review of functional neuroimaging in mood disorders: positron emission tomography and depression. Can J Psychiatr. 2017;42:467–75. https://doi.org/10.1177/070674379704200502.

    Article  Google Scholar 

  5. 5.

    Praharaj SK, Ram D, Arora M. Efficacy of high frequency (rapid) suprathreshold repetitive transcranial magnetic stimulation of right prefrontal cortex in bipolar mania: a randomized sham controlled study. J Affect Disord. 2009;117:146–50. https://doi.org/10.1016/j.jad.2008.12.020.

    Article  PubMed  Google Scholar 

  6. 6.

    Monks PJ, Thompson JM, Bullmore ET, Suckling J, Brammer MJ, Williams SCR, et al. A functional MRI study of working memory task in euthymic bipolar disorder: evidence for task-specific dysfunction. Bipolar Disord. 2004;6:550–64. https://doi.org/10.1111/j.1399-5618.2004.00147.x.

    Article  PubMed  Google Scholar 

  7. 7.

    Wingo AP, Harvey PD, Baldessarini RJ. Neurocognitive impairment in bipolar disorder patients: functional implications. Bipolar Disord. 2009;11:113–25. https://doi.org/10.1111/j.1399-5618.2009.00665.x.

    Article  PubMed  Google Scholar 

  8. 8.

    Bersani FS, Minichino A, Bernabei L, Spagnoli F, Corrado A, Vergnani L, et al. Prefronto-cerebellar tDCS enhances neurocognition in euthymic bipolar patients. Findings from a placebo-controlled neuropsychological and psychophysiological investigation. J Affect Disord. 2017;209:262–9. https://doi.org/10.1016/j.jad.2016.11.037.

    Article  PubMed  Google Scholar 

  9. 9.

    Martin DM, Chan HN, Alonzo A, Green MJ, Mitchell PB, Loo CK. Transcranial direct current stimulation to enhance cognition in euthymic bipolar disorder. Bipolar Disord. 2015;17:849–58. https://doi.org/10.1111/bdi.12350.

    Article  PubMed  Google Scholar 

  10. 10.

    Dondé C, Amad A, Nieto I, et al. Transcranial Direct-Current Stimulation (tDCS) for Depression in bipolar disorder: A systematic review and meta-analysis. Prog Neuropsychopharmacol Biol Psychiatry. 2017;78:123–31. https://doi.org/10.1016/j.pnpbp.2017.05.021.

    Article  PubMed  Google Scholar 

  11. 11.

    Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6:e1000097. https://doi.org/10.1016/j.ijsu.2010.02.007.

    Article  PubMed  PubMed Central  Google Scholar 

  12. 12.

    Bennabi D, Nicolier M, Monnin J, Tio G, Pazart L, Vandel P, et al. Pilot study of feasibility of the effect of treatment with tDCS in patients suffering from treatment-resistant depression treated with escitalopram. Clin Neurophysiol. 2015;126:1185–9. https://doi.org/10.1016/j.clinph.2014.09.026.

    CAS  Article  PubMed  Google Scholar 

  13. 13.

    Pereira Junior Bde S, Tortella G, Lafer B, et al. The bipolar depression electrical treatment trial (BETTER): design, rationale, and objectives of a randomized, sham-controlled trial and data from the pilot study phase. Neural Plast. 2015;2015:1–10. https://doi.org/10.1155/2015/684025.

    CAS  Article  Google Scholar 

  14. 14.

    Brunoni AR, Ferrucci R, Bortolomasi M, Scelzo E, Boggio PS, Fregni F, et al. Interactions between transcranial direct current stimulation (tDCS) and pharmacological interventions in the major depressive episode: findings from a naturalistic study. Eur Psychiatry. 2013;28:356–61. https://doi.org/10.1016/j.eurpsy.2012.09.001.

    CAS  Article  PubMed  Google Scholar 

  15. 15.

    Martin DM, Alonzo A, Ho KA, Player M, Mitchell PB, Sachdev P, et al. Continuation transcranial direct current stimulation for the prevention of relapse in major depression. J Affect Disord. 2013;144:274–8. https://doi.org/10.1016/j.jad.2012.10.012.

    Article  PubMed  Google Scholar 

  16. 16.

    Loo CK, Alonzo A, Martin D, Mitchell PB, Galvez V, Sachdev P. Transcranial direct current stimulation for depression: 3-week, randomised, sham-controlled trial. Br J Psychiatry. 2012;200:52–9. https://doi.org/10.1192/bjp.bp.111.097634.

    Article  PubMed  Google Scholar 

  17. 17.

    Palm U, Schiller C, Fintescu Z, Obermeier M, Keeser D, Reisinger E, et al. Transcranial direct current stimulation in treatment resistant depression: a randomized double-blind, placebo-controlled study. Brain Stimul. 2012;5:242–51. https://doi.org/10.1016/j.brs.2011.08.005.

    CAS  Article  PubMed  Google Scholar 

  18. 18.

    Brunoni AR, Ferrucci R, Bortolomasi M, Vergari M, Tadini L, Boggio PS, et al. Transcranial direct current stimulation (tDCS) in unipolar vs. bipolar depressive disorder. Prog Neuro-Psychopharmacol Biol Psychiatry. 2011a;35:96–101. https://doi.org/10.1016/j.pnpbp.2010.09.010.

    CAS  Article  Google Scholar 

  19. 19.

    Martin DM, Alonzo A, Mitchell PB, Sachdev P, Gálvez V, Loo CK. Fronto-extracephalic transcranial direct current stimulation as a treatment for major depression: an open-label pilot study. J Affect Disord. 2011;134:459–63. https://doi.org/10.1016/j.jad.2011.05.018.

    Article  PubMed  Google Scholar 

  20. 20.

    Loo CK, Martin D, Pigot M, Arul-Anandam P, Mitchell P, Sachdev P. Transcranial direct current stimulation priming of therapeutic repetitive transcranial magnetic stimulation: a pilot study. J ECT. 2009;25:256–60. https://doi.org/10.1097/YCT.0b013e3181a2f87e.

    Article  PubMed  Google Scholar 

  21. 21.

    Sampaio-Junior B, Tortella G, Borrione L, et al. Efficacy and safety of transcranial direct current stimulation as an add-on treatment for bipolar depression: a randomized clinical trial. JAMA Psychiat. 2017;75(2):158–66. https://doi.org/10.1001/jamapsychiatry.2017.4040.

    Article  Google Scholar 

  22. 22.

    Schestatsky P, Janovik N, Lobato MI, Belmonte-de-Abreu P, Schestatsky S, Shiozawa P, et al. Rapid therapeutic response to anodal tDCS of right dorsolateral prefrontal cortex in acute mania. Brain Stimul. 2013;6:701–3. https://doi.org/10.1016/j.brs.2012.10.008.

    Article  PubMed  Google Scholar 

  23. 23.

    Minichino A, Bersani FS, Bernabei L, et al. Prefronto-cerebellar transcranial direct current stimulation improves visuospatial memory, executive functions, and neurological soft signs in patients with euthymic bipolar disorder. Neuropsychiatr Dis Treat. 2015;11:2265–70. https://doi.org/10.2147/NDT.S79108.

    Article  PubMed  PubMed Central  Google Scholar 

  24. 24.

    Minichino A, Bersani FS, Spagnoli F, Corrado A, de Michele F, Calò WK, et al. Prefronto-cerebellar transcranial direct current stimulation improves sleep quality in euthymic bipolar patients: a brief report. Behav Neurol. 2014;2014:1–3. https://doi.org/10.1155/2014/876521.

    Article  Google Scholar 

  25. 25.

    Li MS, Chen YY, Hung GC. Rapid onset of hypomania associated with transcranial direct current stimulation in a patient with bipolar depression. Brain Stimul. 2016;9(6):955–6. https://doi.org/10.1016/j.brs.2016.08.008.

    Article  PubMed  Google Scholar 

  26. 26.

    Brunoni AR, Valiengo L, Zanao T, de Oliveira JF, Bensenor IM, Fregni F. Manic psychosis after sertraline and transcranial direct-current stimulation (2011b). J Neuropsychiatry Clin Neurosci. 2011b;23:e4–5. https://doi.org/10.1176/appi.neuropsych.23.3.E4.

    Article  PubMed  Google Scholar 

  27. 27.

    Gálvez V, Alonzo A, Martin D, et al. Hypomania induction in a patient with bipolar II disorder by transcranial direct current stimulation (tDCS). J ECT. 2011;27:256–8. https://doi.org/10.1097/YCT.0b013e3181a2f87e.

    Article  PubMed  Google Scholar 

  28. 28.

    Baccaro A, Brunoni AR, Bensenor IM, Fregni F. Hypomanic episode in unipolar depression during transcranial direct current stimulation. Acta Neuropsychiatr. 2010;22:316–8. https://doi.org/10.1111/j.1601-5215.2010.00495.x.

    Article  Google Scholar 

  29. 29.

    Benson BE, Willis MW, Ketter TA, Speer A, Kimbrell TA, George MS, et al. Interregional cerebral metabolic associativity during a continuous performance task (part II): differential alterations in bipolar and unipolar disorders. Psychiatry Res. 2008;164:30–47. https://doi.org/10.1016/j.pscychresns.2007.12.016.

    Article  PubMed  Google Scholar 

  30. 30.

    Geoffroy PA, Scott J, Boudebesse C, Lajnef M, Henry C, Leboyer M, et al. Sleep in patients with remitted bipolar disorders: a meta-analysis of actigraphy studies. Acta Psychiatr Scand. 2015;131:89–99. https://doi.org/10.1111/acps.12367.

    CAS  Article  PubMed  Google Scholar 

  31. 31.

    Samalin L, Boyer L, Murru A, Pacchiarotti I, Reinares M, Bonnin CM, et al. Residual depressive symptoms, sleep disturbance and perceived cognitive impairment as determinants of functioning in patients with bipolar disorder. J Affect Disord. 2017;210:280–6. https://doi.org/10.1016/j.jad.2016.12.054.

    Article  PubMed  Google Scholar 

  32. 32.

    Lefaucheur JP, Antal A, Ayache SS, Benninger DH, Brunelin J, Cogiamanian F, et al. Evidence-based guidelines on the therapeutic use of transcranial direct current stimulation (tDCS). Clin Neurophysiol. 2017;128:56–92. https://doi.org/10.1016/j.clinph.2016.10.087.

    Article  PubMed  Google Scholar 

  33. 33.

    Priori A, Hallett M, Rothwell JC. Repetitive transcranial magnetic stimulation or transcranial direct current stimulation? Brain Stimul. 2009;2:241–5. https://doi.org/10.1016/j.brs.2009.02.004.

    Article  PubMed  Google Scholar 

  34. 34.

    Bikson M, Grossman P, Thomas C, Zannou AL, Jiang J, Adnan T, et al. Safety of transcranial direct current stimulation: evidence based update 2016. Brain Stimul. 2016;9:641–61. https://doi.org/10.1016/j.brs.2016.06.004.

    Article  PubMed  PubMed Central  Google Scholar 

  35. 35.

    ClinicalTrials.gov (2012, July 19 –). tDCS as an add-on treatment for resistant major depression in Uni- and bipolar patients (STICODEP). Identifier NCT01644747. Retrieved April 9, 2018 from: https://clinicaltrials.gov/ct2/show/study/NCT01644747

  36. 36.

    ClinicalTrials.gov (2017, September 19 – ). The effects of tDCS on depressive symptoms, neurocognitive function and HRV in unipolar depression and bipolar depression. Identifier NCT03287037. Retrieved April 9, 2018 from: https://clinicaltrials.gov/ct2/show/study/NCT03287037

  37. 37.

    Bikson M, Brunoni AR, Charvet LE, et al. Rigor and reproducibility in research with transcranial electrical stimulation: An NIMH-sponsored workshop. Brain Stimul 2017;1–16. https://doi.org/10.1016/j.brs.2017.12.008

    Article  Google Scholar 

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Acknowledgments

We are very grateful to Bennabi D., Martin D. and Palm U. who kindly replied to our queries and provided data about their studies.

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This Psychiatric Quarterly submission did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Correspondence to Clément Dondé.

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Pierre A. Geoffroy has received travel awards or financial compensation from AstraZeneca, Lundbeck, Menarini France and Otsuka.

Author Clément Dondé, Nicholas H. Neufeld and Pierre A. Geoffroy declare that they have no conflicts of interest pertaining to this Psychiatric Quarterly submission.

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This Psychiatric Quarterly submission does not contain any studies with human participants or animals performed by any of the authors.

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Dondé, C., Neufeld, N.H. & Geoffroy, P.A. The Impact of Transcranial Direct Current Stimulation (tDCS) on Bipolar Depression, Mania, and Euthymia: a Systematic Review of Preliminary Data. Psychiatr Q 89, 855–867 (2018). https://doi.org/10.1007/s11126-018-9584-5

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Keywords

  • Bipolar disorders
  • Mood disorder
  • Depression
  • Neurocognitive impairment
  • Transcranial direct current stimulation
  • Sleep