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A Systematic Review and Meta-Analysis of Randomized Sham-Controlled Trials of Repetitive Transcranial Magnetic Stimulation for Bipolar Disorder

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Abstract

Background: Repetitive transcranial magnetic stimulation (rTMS) is effective in treating unipolar depression. However, the efficacy of rTMS in bipolar disorder (BD) is unclear. This meta-analysis aimed to examine the efficacy and tolerability of rTMS for both depressive and manic phases in BD. Methods: MEDLINE, EMBASE, PsycINFO, CENTRAL databases were searched for controlled trials on treatment of BD with rTMS. Primary outcomes included changes in depression or mania scores, response and remission rates. Secondary outcomes included quality of life and functioning assessment. We used random-effects model, Hedge’s g, risk differences (RDs) and the number needed to treat (NNT). Results: Eleven randomized sham-controlled studies were included, with a total of 345 patients with BD (bipolar depression = 257, mania = 86, mixed affective = 2). Trials of rTMS in bipolar depression (N = 8) demonstrated small but significant improvement in depression scores [standardized mean difference = 0.302, p < 0.05], compared to control group. Furthermore, rTMS brought a higher remission rate than sham-controls [RD = 0.104 ± 0.044, p < 0.05, NNT = 10; and a trend of greater response rate [RD = 0.074 ± 0.039, p = 0.06]. Results were inconclusive for effect of rTMS in mania. In both depressive and manic groups, no serious adverse events were reported. Risk of treatment-emergent mania appeared low. Limitations: There was limited number of eligible primary studies, with variable randomization procedures. Conclusion: rTMS appears safe and effective in treating bipolar depression. More stringent RCTs are necessary for concrete conclusion about efficacy in mania.

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References

  1. Merikangas KR, Jin R, He JP, Kessler RC, Lee S, Sampson NA, et al. Prevalence and correlates of bipolar spectrum disorder in the world mental health survey initiative. Arch Gen Psychiatry. 2011;68(3):241–51.

    PubMed  Google Scholar 

  2. Greenberg S, Rosenblum KL, McInnis MG, Muzik M. The role of social relationships in bipolar disorder: a review. Psychiatry Res. 2014;219(2):248–54.

    PubMed  Google Scholar 

  3. Pompili M, Harnic D, Gonda X, Forte A, Dominici G, Innamorati M, et al. Impact of living with bipolar patients: making sense of caregivers' burden. World J Psychiatry. 2014;4(1):1–12.

    PubMed  Google Scholar 

  4. Kemp DE. Managing the side effects associated with commonly used treatments for bipolar depression. J Affect Disord. 2014;169:S34–44.

    CAS  PubMed  Google Scholar 

  5. Sachs GS, Nierenberg AA, Calabrese JR, Marangell LB, Wisniewski SR, Gyulai L, et al. Effectiveness of adjunctive antidepressant treatment for bipolar depression. N Engl J Med. 2007;356(17):1711–22.

    CAS  PubMed  Google Scholar 

  6. Lefaucheur J-P, 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(11):2150–206.

    Google Scholar 

  7. Nahas Z, Molloy MA, Hughes PL, Oliver NC, Arana GW, Risch SC, et al. Repetitive transcranial magnetic stimulation: perspectives for application in the treatment of bipolar and unipolar disorders. Bipolar Disord. 1999;1(2):73–80.

    CAS  PubMed  Google Scholar 

  8. Hardy S, Bastick L, O'Neill-Kerr A, Sabesan P, Lankappa S, Palaniyappan L. Transcranial magnetic stimulation in clinical practice. BJPsych Advances. 2016;22(6):373–9.

    Google Scholar 

  9. Allan CL, Herrmann LL, Ebmeier KP. Transcranial magnetic stimulation in the management of mood disorders. Neuropsychobiology. 2011;64(3):163–9.

    PubMed  Google Scholar 

  10. Fountoulakis KN, Grunze H, Panagiotidis P, Kaprinis G. Treatment of bipolar depression: an update. J Affect Disord. 2008;109(1–2):21–34.

    PubMed  Google Scholar 

  11. Dell'Osso B, Mundo E, D'Urso N, Pozzoli S, Buoli M, Ciabatti M, et al. Augmentative repetitive navigated transcranial magnetic stimulation (rTMS) in drug-resistant bipolar depression. Bipolar Disord. 2009;11(1):76–81.

    PubMed  Google Scholar 

  12. Dolberg OT, Dannon PN, Schreiber S, Grunhaus L. Transcranial magnetic stimulation in patients with bipolar depression: a double blind, controlled study. Bipolar Disord. 2002;4 Suppl 1:94-95.Fountoulakis KN, Grunze H, Panagiotidis P, Kaprinis G. treatment of bipolar depression: an update. J Affect Disord. 2008;109(1–2):21–34.

    Google Scholar 

  13. Tamas RL, Menkes D, El-Mallakh RS. Stimulating research: a prospective, randomized, double-blind, sham-controlled study of slow transcranial magnetic stimulation in depressed bipolar patients. J Neuropsychiatry Clin Neurosci. 2007;19(2):198–9.

    PubMed  Google Scholar 

  14. Beynel L, Chauvin A, Guyader N, et al. What saccadic eye movements tell us about TMS-induced neuromodulation of the DLPFC and mood changes: a pilot study in bipolar disorders. Front Integr Neurosci. 2014;8:65.

    PubMed  Google Scholar 

  15. Nahas Z, Kozel FA, Li X, Anderson B, George MS. Left prefrontal transcranial magnetic stimulation (TMS) treatment of depression in bipolar affective disorder: a pilot study of acute safety and efficacy. Bipolar Disord. 2003;5(1):40–7.

    PubMed  Google Scholar 

  16. Grisaru N, Chudakov B, Yaroslavsky Y, Belmaker RH. Transcranial magnetic stimulation in mania: a controlled study. Am J Psychiatry. 1998;155(11):1608–10.

    CAS  PubMed  Google Scholar 

  17. Michael N, Erfurth A. Treatment of bipolar mania with right prefrontal rapid transcranial magnetic stimulation. J Affect Disord. 2004;78(3):253–7.

    PubMed  Google Scholar 

  18. Saba G, Rocamora JF, Kalalou K, et al. Repetitive transcranial magnetic stimulation as an add-on therapy in the treatment of mania: a case series of eight patients. Psychiatry Res. 2004;128(2):199–202.

    Google Scholar 

  19. 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(3):146–50 Saba G, Rocamora JF, Kalalou K, et al. repetitive transcranial magnetic stimulation as an add-on therapy in the treatment of mania: a case series of eight patients. Psychiatry Res 2004;128(2):199–202.

    PubMed  Google Scholar 

  20. Kaptsan A, Yaroslavsky Y, Applebaum J, Belmaker RH, Grisaru N. Right prefrontal TMS versus sham treatment of mania: a controlled study. Bipolar Disord. 2003;5(1):36–9.

    PubMed  Google Scholar 

  21. McGirr A, Karmani S, Arsappa R, Berlim MT, Thirthalli J, Muralidharan K, et al. Clinical efficacy and safety of repetitive transcranial magnetic stimulation in acute bipolar depression. World Psychiatry. 2016;15(1):85–6.

    PubMed  Google Scholar 

  22. Fitzgerald PB, Hoy KE, Elliot D, McQueen S, Wambeek LE, Daskalakis ZJ. A negative double-blind controlled trial of sequential bilateral rTMS in the treatment of bipolar depression. J Affect Disord. 2016;198:158–62.

    PubMed  Google Scholar 

  23. Hu SH, Lai JB, Xu DR, Qi HL, Peterson BS, Bao AM, et al. Efficacy of repetitive transcranial magnetic stimulation with quetiapine in treating bipolar II depression: a randomized, double-blinded, control study. Sci Rep. 2016;6:30537.

    CAS  PubMed  Google Scholar 

  24. Li N, Wang XY, Qin ZZ, Song M. A 4-week single-blind randomized controlled trial of repetitive transcranial magnetic stimulation combined with lithium and quetiapine in treatment of patients with bipolar depression. Chin Ment Health J. 2013;12:896–900.

    Google Scholar 

  25. Tavares DF, Myczkowski ML, Alberto RL, Valiengo L, Rios RM, Gordon P, et al. Treatment of bipolar depression with deep TMS: results from a double-blind, randomized, parallel group, Sham-Controlled Clinical Trial. Neuropsychopharmacology. 2017;42(13):2593–601.

    PubMed  Google Scholar 

  26. Citrome L. Number needed to treat: what it is and what it Isn't, and why every clinician should know how to calculate it. J Clin Psychiatry. 2011;72:412–3.

    PubMed  Google Scholar 

  27. Bown MJ, Sutton AJ. Quality control in systematic reviews and meta-analyses. Eur J Vasc Endovasc Surg. 2010;40(5):669–77.

    CAS  PubMed  Google Scholar 

  28. Pathak V, Sinha VK, Praharaj SK. Efficacy of adjunctive high frequency repetitive Transcranial magnetic stimulation of right prefrontal cortex in adolescent mania: a randomized sham-controlled study. Clin Psychopharmacol Neurosci. 2015;13(3):245–9.

    PubMed  Google Scholar 

  29. Speer AM, Wassermann EM, Benson BE, Herscovitch P, Post RM. Antidepressant efficacy of high and low frequency rTMS at 110% of motor threshold versus sham stimulation over left prefrontal cortex. Brain Stimul. 2014;7(1):36–41.

    PubMed  Google Scholar 

  30. Berlim MT, van den Eynde F, Tovar-Perdomo S, Daskalakis ZJ. Response, remission and drop-out rates following high-frequency repetitive transcranial magnetic stimulation (rTMS) for treating major depression: a systematic review and meta-analysis of randomized, double-blind and sham-controlled trials. Psychol Med. 2014;44(2):225–39.

    CAS  PubMed  Google Scholar 

  31. Sibbald B, Roland M. Understanding controlled trials. Why are randomised controlled trials important? BMJ. 1998;316(7126):201.

    CAS  PubMed  Google Scholar 

  32. Chen JJ, Liu Z, Zhu D, Li Q, Zhang H, Huang H, et al. Bilateral vs. unilateral repetitive transcranial magnetic stimulation in treating major depression: a meta-analysis of randomized controlled trials. Psychiatry Res. 2014;219(1):51–7.

    PubMed  Google Scholar 

  33. Cohen RB, Brunoni AR, Boggio PS, Fregni F. Clinical predictors associated with duration of repetitive transcranial magnetic stimulation treatment for remission in bipolar depression: a naturalistic study. J Nerv Ment Dis. 2010;198(9):679–81.

    PubMed  Google Scholar 

  34. Rostami R, Kazemi R, Nitsche MA, Gholipour F, Salehinejad MA. Clinical and demographic predictors of response to rTMS treatment in unipolar and bipolar depressive disorders. Clin Neurophysiol. 2017;128(10):1961–70.

    PubMed  Google Scholar 

  35. Altshuler LL, Bookheimer SY, Townsend J, Proenza MA, Eisenberger N, Sabb F, et al. Blunted activation in orbitofrontal cortex during mania: a functional magnetic resonance imaging study. Biol Psychiatry. 2005;58(10):763–9.

    PubMed  Google Scholar 

  36. Brady RO Jr, Tandon N, Masters GA, et al. Differential brain network activity across mood states in bipolar disorder. J Affect Disord. 2017;207:367–76.

    PubMed  Google Scholar 

  37. Fornaro M, Anastasia A, Novello S, Fusco A, Solmi M, Monaco F, et al. Incidence, prevalence and clinical correlates of antidepressant-emergent mania in bipolar depression: a systematic review and meta-analysis. Bipolar Disord. 2018;20(3):195–227.

    PubMed  Google Scholar 

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Author notes

  1. Maggie M. K. Tee and C. H. Au contributed equally to this work.

Authors and Affiliations

  1. Department of Psychiatry, Kwai Chung Hospital, 3-15 Kwai Chung Hospital Road, Hong Kong, China

    Maggie M. K. Tee

  2. Department of Psychiatry, Queen Mary Hospital, Hong Kong, China

    C. H. Au

Authors
  1. Maggie M. K. Tee
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  2. C. H. Au
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Corresponding author

Correspondence to Maggie M. K. Tee.

Ethics declarations

This research is a systematic review and meta-analysis, it does not involve direct intervention on human participants or animals, therefore informed consent is not necessary. This study is not funded.

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Appendix 1 Search terms in different search engines

Appendix 1 Search terms in different search engines

The full search strategy used in CENTRAL was shown as follows:

  • #1. MeSH descriptor: [Bipolar Disorder] explode all trees

  • #2. Bipolar near disorder

  • #3. Bipolar

  • #4. Mani*

  • #5. Depressi*

  • #6. Manic-depressi*

  • #7. BAD

  • #8. BD

  • #9. Affective

  • #10. Mixed near affective

  • #11. Cyclothymi*

  • #12. Mood near disorder

  • #13. Mood near swing

  • #14. Elat*

  • #15. #1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10 OR #11 OR #12 OR #13 OR #14

  • #16. MeSH descriptor: [Transcranial Magnetic Stimulation] explode all trees

  • #17. Transcranial near magnetic near stimulation

  • #18. TMS

  • #19. rTMS

  • #20. dTMS

  • #21. Theta near burst near stimulation

  • #22. Thetaburst near stimulation

  • #23. TBS

  • #24. iTBS

  • #25. cTBS

  • #26. Brain near stimulation

  • #27. Neurostimulat*

  • #28. Neuromodulat*

  • #29. Magnetic near stimulation

  • #30. #16 OR #17 OR #18 OR #19 OR #20 OR #21 OR #22 OR #23 OR #24 OR #25 OR #26 OR #27 OR #28 OR #29

  • #31. #15 AND #30

The full search strategy used in Pubmed was shown as follows:

(((((((((((((((bipolar adj3 disorder) OR bipolar) OR BAD) OR BD) OR manic-depressi*) OR mania) OR manic) OR affective) OR mood adj2 disorder) OR mood swing) OR depressi*) OR cyclothymi*) OR elat*) OR mixed affective)) AND (((((((((((((transcranial adj2 magnetic adj2 stimulation) OR TMS) OR rTMS) OR dTMS) OR theta adj2 burst adj2 stimulation) OR thetaburst adj2 stimulation) OR TBS) OR iTBS) OR cTBS) OR brain adj3 stimulation) OR neurostimulat*) OR neuromodulat*) OR magnetic adj2 stimulation)

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Tee, M.M.K., Au, C.H. A Systematic Review and Meta-Analysis of Randomized Sham-Controlled Trials of Repetitive Transcranial Magnetic Stimulation for Bipolar Disorder. Psychiatr Q 91, 1225–1247 (2020). https://doi.org/10.1007/s11126-020-09822-6

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  • DOI: https://doi.org/10.1007/s11126-020-09822-6

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