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Primary Care Companion for CNS Disorders Primary Care Companion for CNS Disorders

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Meta-Analysis September 26, 2023

Effectiveness of Repetitive Transcranial Magnetic Stimulation in Depression, Schizophrenia, and Obsessive-Compulsive Disorder: An Umbrella Meta-Analysis

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Prim Care Companion CNS Disord 2023;25(5):22r03423

ABSTRACT

Objective: To analyze the safety and efficacy of repetitive transcranial magnetic stimulation (rTMS) for major depressive disorder, schizophrenia, and obsessive-compulsive disorder (OCD) via umbrella meta-analysis.

Data Sources: Meta-analysis studies were searched in PubMed from inception to May 2021 using the keywords anxiety, depression, ADHD, schizophrenia, mood disorder, OCD, psychiatric disorders, GAD, bipolar disorders, ASD, PTSD, transcranial magnetic stimulation, transcranial, magnetic, stimulation. PRISMA guidelines were followed.

Study Selection: Abstracts and full-length articles were reviewed for meta-analysis studies with data on the safety and efficacy of rTMS and sham and were collected for quantitative analysis. The full texts of all identified studies were independently screened and assessed to determine eligibility. Any disagreement was resolved through consensus.

Data Extraction: The descriptive variables extracted included the author names, study year, sample size, studies included in the meta-analysis, study period, and type of intervention.

Results: 28 meta-analyses were included; 13 were on treatment-resistant depression, 9 on schizophrenia, and 6 on OCD. In treatment-resistant depression, the rTMS group had higher odds of response compared to sham (odds ratio [OR] = 3.27; 95% CI, 2.76–3.87; P < .00001) and higher odds of remission (secondary outcome) (OR = 2.83; 95% CI, 2.33–3.45; P < .00001). rTMS was superior to sham in the reduction of negative symptoms of schizophrenia (mean difference [MD]: 0.47; 95% CI, 0.23–0.7; P < .0001). However, no significant difference was found between the effects of rTMS and sham on auditory hallucinations (MD: 0.24; 95% CI, 0.26–0.74; P = .35), which resulted in 94% heterogeneity. TMS was better than sham in reducing the severity of OCD symptoms (MD: 0.81; 95% CI, 0.53–1.10; P < .00001).

Conclusions: The effectiveness of rTMS for symptom reduction in various psychiatric disorders is associated with differences in neuropathology, disease-specific target site, and frequency of rTMS.

Prim Care Companion CNS Disord 2023;25(5):22r03423

Author affiliations are listed at the end of this article.

  1. National Institute of Mental Health. Major depression. Accessed August 24, 2021. https://www.nimh.nih.gov/health/statistics/major-depression
  2. National Institute of Mental Health. Schizophrenia. Accessed August 24, 2021. https://www.nimh.nih.gov/health/statistics/schizophrenia#part_154880
  3. National Institute of Mental Health. Obsessive-compulsive disorder. Accessed August 24, 2021. https://www.nimh.nih.gov/health/statistics/obsessive-compulsive-disorder-ocd
  4. Buchanan DM, Robaey P, D’Angiulli A. What do we know about transcranial direct current stimulation for major depression? Brain Sci. 2020;10(8):480. PubMed CrossRef
  5. Moffa AH, Brunoni AR, Nikolin S, et al. Transcranial direct current stimulation in psychiatric disorders: a comprehensive review. Psychiatr Clin North Am. 2018;41(3):447–463. PubMed CrossRef
  6. Haller N, Hasan A, Padberg F, et al. Transkranielle elektrische Hirnstimulationsverfahren zur Behandlung der Negativsymptomatik bei Schizophrenie. (Transcranial electrical brain stimulation methods for treatment of negative symptoms in schizophrenia). Nervenarzt. 2022;93(1):41–50. PubMed CrossRef
  7. Dunlop K, Hanlon CA, Downar J. Noninvasive brain stimulation treatments for addiction and major depression. Ann N Y Acad Sci. 2017;1394(1):31–54. PubMed CrossRef
  8. Trojak B, Sauvaget A, Fecteau S, et al. Outcome of non-invasive brain stimulation in substance use disorders: a review of randomized sham-controlled clinical trials. J Neuropsychiatry Clin Neurosci. 2017;29(2):105–118. PubMed CrossRef
  9. Boes AD, Kelly MS, Trapp NT, et al. Noninvasive brain stimulation: challenges and opportunities for a new clinical specialty. J Neuropsychiatry Clin Neurosci. 2018;30(3):173–179. PubMed CrossRef
  10. Barker AT, Jalinous R, Freeston IL. Non-invasive magnetic stimulation of human motor cortex. Lancet. 1985;325(8437):1106–1107. PubMed CrossRef
  11. Wagner T, Valero-Cabre A, Pascual-Leone A. Noninvasive human brain stimulation. Annu Rev Biomed Eng. 2007;9(1):527–565. PubMed CrossRef
  12. Maeda F, Keenan JP, Tormos JM, et al. Modulation of corticospinal excitability by repetitive transcranial magnetic stimulation. Clin Neurophysiol. 2000;111(5):800–805. PubMed CrossRef
  13. Klomjai W, Katz R, Lackmy-Vallée A. Basic principles of transcranial magnetic stimulation (TMS) and repetitive TMS (rTMS). Ann Phys Rehabil Med. 2015;58(4):208–213. PubMed CrossRef
  14. Leggett LE, Soril LJJ, Coward S, et al. Repetitive transcranial magnetic stimulation for treatment-resistant depression in adult and youth populations: a systematic literature review and meta-analysis. Prim Care Companion CNS Disord. 2015;17(6):15r01807. PubMed CrossRef
  15. Martin JLR, Barbanoj MJ, Schlaepfer TE, et al. Repetitive transcranial magnetic stimulation for the treatment of depression: systematic review and meta-analysis. Br J Psychiatry. 2003;182(6):480–491. PubMed CrossRef
  16. Berlim MT, Neufeld NH, Van den Eynde F. Repetitive transcranial magnetic stimulation (rTMS) for obsessive-compulsive disorder (OCD): an exploratory meta-analysis of randomized and sham-controlled trials. J Psychiatr Res. 2013;47(8):999–1006. PubMed CrossRef
  17. Yesavage JA, Fairchild JK, Mi Z, et al. VA Cooperative Studies Program Study Team. Effect of repetitive transcranial magnetic stimulation on treatment-resistant major depression in us veterans: a randomized clinical trial. JAMA Psychiatry. 2018;75(9):884–893. PubMed CrossRef
  18. Haghighi M, Shayganfard M, Jahangard L, et al. Repetitive transcranial magnetic stimulation (rTMS) improves symptoms and reduces clinical illness in patients suffering from OCD: results from a single-blind, randomized clinical trial with sham cross-over condition. J Psychiatr Res. 2015;68:238–244. PubMed CrossRef
  19. National Institute of Mental Health. Brain stimulation therapies. Accessed August 24, 2021. https://www.nimh.nih.gov
  20. Berlim MT, van den Eynde F, Tovar-Perdomo S, et al. 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):225–239. PubMed CrossRef
  21. Martin JL, Barbanoj MJ, Pérez V, et al. Transcranial magnetic stimulation for the treatment of obsessive-compulsive disorder. Cochrane Database Syst Rev. 2003;2003(3):CD003387. PubMed CrossRef
  22. Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372(71):n71. PubMed CrossRef
  23. Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960;23(1):56–62. PubMed CrossRef
  24. Montgomery SA, Asberg M. A new depression scale designed to be sensitive to change. Br J Psychiatry. 1979;134(4):382–389. PubMed CrossRef
  25. Goodman WK, Price LH, Rasmussen SA, et al. The Yale-Brown Obsessive Compulsive Scale, I: development, use, and reliability. Arch Gen Psychiatry. 1989;46(11):1006–1011. PubMed CrossRef
  26. Kay SR, Fiszbein A, Opler LA. The Positive and Negative Syndrome Scale (PANSS) for schizophrenia. Schizophr Bull. 1987;13(2):261–276. PubMed CrossRef
  27. Andreasen NC. Negative symptoms in schizophrenia: definition and reliability. Arch Gen Psychiatry. 1982;39(7):784–788. PubMed CrossRef
  28. Overall JE. The Brief Psychiatric Rating Scale (BPRS): recent developments in ascertainment and scaling. Psychopharmacol Bull. 1988;24:97–100.
  29. Hoffman RE, Gueorguieva R, Hawkins KA, et al. Temporoparietal transcranial magnetic stimulation for auditory hallucinations: safety, efficacy and moderators in a 50-patient sample. Biol Psychiatry. 2005;58(2):97–104. PubMed CrossRef
  30. Berlim MT, Van den Eynde F, Daskalakis ZJ. A systematic review and meta-analysis on the efficacy and acceptability of bilateral repetitive transcranial magnetic stimulation (rTMS) for treating major depression. Psychol Med. 2013;43(11):2245–2254. PubMed CrossRef
  31. Berlim MT, Van den Eynde F, Jeff Daskalakis Z. Clinically meaningful efficacy and acceptability of low-frequency repetitive transcranial magnetic stimulation (rTMS) for treating primary major depression: a meta-analysis of randomized, double-blind and sham-controlled trials. Neuropsychopharmacology. 2013;38(4):543–551. PubMed CrossRef
  32. Brunoni AR, Chaimani A, Moffa AH, et al. Repetitive transcranial magnetic stimulation for the acute treatment of major depressive episodes: a systematic review with network meta-analysis. JAMA Psychiatry. 2017;74(2):143–152. PubMed CrossRef
  33. Mutz J, Edgcumbe DR, Brunoni AR, et al. Efficacy and acceptability of non-invasive brain stimulation for the treatment of adult unipolar and bipolar depression: a systematic review and meta-analysis of randomised sham-controlled trials. Neurosci Biobehav Rev. 2018;92:291–303. PubMed CrossRef
  34. Zhang YQ, Zhu D, Zhou XY, et al. Bilateral repetitive transcranial magnetic stimulation for treatment-resistant depression: a systematic review and meta-analysis of randomized controlled trials. Braz J Med Biol Res. 2015;48(3):198–206. PubMed CrossRef
  35. Couturier JL. Efficacy of rapid-rate repetitive transcranial magnetic stimulation in the treatment of depression: a systematic review and meta-analysis. J Psychiatry Neurosci. 2005;30(2):83–90. PubMed
  36. Teng S, Guo Z, Peng H, et al. High-frequency repetitive transcranial magnetic stimulation over the left DLPFC for major depression: session-dependent efficacy: a meta-analysis. Eur Psychiatry. 2017;41(1):75–84. PubMed CrossRef
  37. Kedzior KK, Reitz SK, Azorina V, et al. Durability of the antidepressant effect of the high-frequency repetitive transcranial magnetic stimulation (rTMS) in the absence of maintenance treatment in major depression: a systematic review and meta-analysis of 16 double-blind, randomized, sham-controlled trials. Depress Anxiety. 2015;32(3):193–203. PubMed CrossRef
  38. Lam RW, Chan P, Wilkins-Ho M, et al. Repetitive transcranial magnetic stimulation for treatment-resistant depression: a systematic review and meta-analysis. Can J Psychiatry. 2008;53(9):621–631. PubMed CrossRef
  39. Sehatzadeh S, Daskalakis ZJ, Yap B, et al. Unilateral and bilateral repetitive transcranial magnetic stimulation for treatment-resistant depression: a meta-analysis of randomized controlled trials over 2 decades. J Psychiatry Neurosci. 2019;44(3):151–163. PubMed CrossRef
  40. Perera MPN, Mallawaarachchi S, Miljevic A, et al. Repetitive transcranial magnetic stimulation for obsessive-compulsive disorder: a meta-analysis of randomized, sham-controlled trials. Biol Psychiatry Cogn Neurosci Neuroimaging. 2021;6(10):947–960. PubMed CrossRef
  41. Rehn S, Eslick GD, Brakoulias V. A meta-analysis of the effectiveness of different cortical targets used in repetitive transcranial magnetic stimulation (rTMS) for the treatment of obsessive-compulsive disorder (OCD). Psychiatr Q. 2018;89(3):645–665. PubMed CrossRef
  42. Ma Z-R, Shi L-J. Repetitive transcranial magnetic stimulation (rTMS) augmentation of selective serotonin reuptake inhibitors (SSRIs) for SSRI-resistant obsessive-compulsive disorder (OCD): a meta-analysis of randomized controlled trials. Int J Clin Exp Med. 2014;7(12):4897–4905. PubMed
  43. Trevizol AP, Shiozawa P, Cook IA, et al. Transcranial magnetic stimulation for obsessive-compulsive disorder: an updated systematic review and meta-analysis. J ECT. 2016;32(4):262–266. PubMed CrossRef
  44. Zhou DD, Wang W, Wang GM, et al. An updated meta-analysis: short-term therapeutic effects of repeated transcranial magnetic stimulation in treating obsessive-compulsive disorder. J Affect Disord. 2017;215:187–196. PubMed CrossRef
  45. Aleman A, Enriquez-Geppert S, Knegtering H, et al. Moderate effects of noninvasive brain stimulation of the frontal cortex for improving negative symptoms in schizophrenia: meta-analysis of controlled trials. Neurosci Biobehav Rev. 2018;89:111–118. PubMed CrossRef
  46. Freitas C, Fregni F, Pascual-Leone A. Meta-analysis of the effects of repetitive transcranial magnetic stimulation (rTMS) on negative and positive symptoms in schizophrenia. Schizophr Res. 2009;108(1–3):11–24. PubMed CrossRef
  47. He H, Lu J, Yang L, et al. Repetitive transcranial magnetic stimulation for treating the symptoms of schizophrenia: a PRISMA-compliant meta-analysis. Clin Neurophysiol. 2017;128(5):716–724. PubMed CrossRef
  48. Dlabač-de Lange JJ, Knegtering R, Aleman A. Repetitive transcranial magnetic stimulation for negative symptoms of schizophrenia: review and meta-analysis. J Clin Psychiatry. 2010;71(4):411–418. PubMed CrossRef
  49. Shi C, Yu X, Cheung EFC, et al. Revisiting the therapeutic effect of rTMS on negative symptoms in schizophrenia: a meta-analysis. Psychiatry Res. 2014;215(3):505–513. PubMed CrossRef
  50. Aleman A, Sommer IE, Kahn RS. Efficacy of slow repetitive transcranial magnetic stimulation in the treatment of resistant auditory hallucinations in schizophrenia: a meta-analysis. J Clin Psychiatry. 2007;68(3):416–421.  PubMed CrossRef
  51. Li J, Cao X, Liu S, et al. Efficacy of repetitive transcranial magnetic stimulation on auditory hallucinations in schizophrenia: a meta-analysis. Psychiatry Res. 2020;290:113141. PubMed CrossRef
  52. Otani VHO, Shiozawa P, Cordeiro Q, et al. A systematic review and meta-analysis of the use of repetitive transcranial magnetic stimulation for auditory hallucinations treatment in refractory schizophrenic patients. Int J Psychiatry Clin Pract. 2015;19(4):228–232. PubMed CrossRef
  53. Zhang Y, Liang W, Yang S, et al. Repetitive transcranial magnetic stimulation for hallucination in schizophrenia spectrum disorders: a meta-analysis. Neural Regen Res. 2013;8(28):2666–2676. PubMed.
  54. Wells GA, Shea B, O'Connell D, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomized studies in meta-analyses. Accessed August 24, 2021. https://www.ohri.ca/programs/clinical_epidemiology/oxford.asp
  55. Baeken C, De Raedt R. Neurobiological mechanisms of repetitive transcranial magnetic stimulation on the underlying neurocircuitry in unipolar depression. Dialogues Clin Neurosci. 2011;13(1):139–145. PubMed CrossRef
  56. Noda Y, Silverstein WK, Barr MS, et al. Neurobiological mechanisms of repetitive transcranial magnetic stimulation of the dorsolateral prefrontal cortex in depression: a systematic review. Psychol Med. 2015;45(16):3411–3432. PubMed CrossRef
  57. Paillère Martinot ML, Martinot J-L, Ringuenet D, et al. Baseline brain metabolism in resistant depression and response to transcranial magnetic stimulation. Neuropsychopharmacology. 2011;36(13):2710–2719. PubMed CrossRef
  58. Concerto C, Lanza G, Cantone M, et al. Repetitive transcranial magnetic stimulation in patients with drug-resistant major depression: a six-month clinical follow-up study. Int J Psychiatry Clin Pract. 2015;19(4):252–258. PubMed CrossRef
  59. Blumberger DM, Mulsant BH, Fitzgerald PB, et al. A randomized double-blind sham-controlled comparison of unilateral and bilateral repetitive transcranial magnetic stimulation for treatment-resistant major depression. World J Biol Psychiatry. 2012;13(6):423–435. PubMed CrossRef
  60. Tik M, Hoffmann A, Sladky R, et al. Towards understanding rTMS mechanism of action: stimulation of the DLPFC causes network-specific increase in functional connectivity. Neuroimage. 2017;162:289–296. PubMed CrossRef
  61. Brown JC, DeVries WH, Korte JE, et al. NMDA receptor partial agonist, d-cycloserine, enhances 10 Hz rTMS-induced motor plasticity, suggesting long-term potentiation (LTP) as underlying mechanism. Brain Stimul. 2020;13(3):530–532. PubMed CrossRef
  62. Shang Y, Wang X, Li F, et al. rTMS ameliorates prenatal stress-induced cognitive deficits in male-offspring rats associated with BDNF/TrkB signaling pathway. Neurorehabil Neural Repair. 2019;33(4):271–283. PubMed CrossRef
  63. Lim S-H, Shin S, Kim M-H, et al. Depression-like behaviors induced by defective PTPRT activity through dysregulated synaptic functions and neurogenesis. J Cell Sci. 2020;133(20):jcs.243972. PubMed CrossRef
  64. Kennedy NI, Lee WH, Frangou S. Efficacy of non-invasive brain stimulation on the symptom dimensions of schizophrenia: a meta-analysis of randomized controlled trials. Eur Psychiatry. 2018;49:69–77. PubMed CrossRef
  65. Stanford AD, Sharif Z, Corcoran C, et al. rTMS strategies for the study and treatment of schizophrenia: a review. Int J Neuropsychopharmacol. 2008;11(4):563–576. PubMed CrossRef
  66. Walton E, Hibar DP, van Erp TGM, et al. Karolinska Schizophrenia Project Consortium (KaSP). Prefrontal cortical thinning links to negative symptoms in schizophrenia via the ENIGMA consortium. Psychol Med. 2018;48(1):82–94. PubMed CrossRef
  67. Dlabac-de Lange JJ, Liemburg EJ, Bais L, et alD.L. JJ. Effect of rTMS on brain activation in schizophrenia with negative symptoms: a proof-of-principle study. Schizophr Res. 2015;168(1-2):475–482. PubMed CrossRef
  68. Tandt HLN, Van de Velde N, De Witte S, et al. Is twice daily LF-rTMS a viable treatment option for treatment-resistant OCD? Results from an open-label feasibility study. Eur Arch Psychiatry Clin Neurosci. 2021;271(1):211–214. PubMed CrossRef
  69. Rostami R, Kazemi R, Jabbari A, et al. Efficacy and clinical predictors of response to rTMS treatment in pharmacoresistant obsessive-compulsive disorder (OCD): a retrospective study. BMC Psychiatry. 2020;20(1):372. PubMed CrossRef
  70. Beucke JC, Sepulcre J, Talukdar T, et al. Abnormally high degree connectivity of the orbitofrontal cortex in obsessive-compulsive disorder. JAMA Psychiatry. 2013;70(6):619–629. PubMed CrossRef
  71. Garg H, Kumar S, Singh S, et al. New onset obsessive compulsive disorder following high frequency repetitive transcranial magnetic stimulation over left dorsolateral prefrontal cortex for treatment of negative symptoms in a patient with schizophrenia. Clin Psychopharmacol Neurosci. 2019;17(3):443–445. PubMed CrossRef
  72. Rapinesi C, Kotzalidis GD, Ferracuti S, et al. Brain stimulation in obsessive-compulsive disorder (OCD): a systematic review. Curr Neuropharmacol. 2019;17(8):787–807. PubMed CrossRef
  73. Dunlop K, Woodside B, Olmsted M, et al. Reductions in cortico-striatal hyperconnectivity accompany successful treatment of obsessive-compulsive disorder with dorsomedial prefrontal rTMS. Neuropsychopharmacology. 2016;41(5):1395–1403. PubMed CrossRef
  74. McClintock SM, Reti IM, Carpenter LL, et al. American Psychiatric Association Council on Research Task Force on Novel Biomarkers and Treatments. Consensus recommendations for the clinical application of repetitive transcranial magnetic stimulation (rTMS) in the treatment of depression. J Clin Psychiatry. 2018;79(1):35–48. PubMed CrossRef
  75. Taylor JJ, Borckardt JJ, George MS. Endogenous opioids mediate left dorsolateral prefrontal cortex rTMS-induced analgesia. Pain. 2012;153(6):1219–1225. PubMed CrossRef
  76. Rossi S, Hallett M, Rossini PM, et al. Safety of TMS Consensus Group. Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. Clin Neurophysiol. 2009;120(12):2008–2039. PubMed CrossRef
  77. Dolberg OT, Schreiber S, Grunhaus L, et al. Transcranial magnetic stimulation-induced switch into mania: a report of two cases. Biol Psychiatry. 2001;49(5):468–470. PubMed CrossRef
  78. Carpenter LL, Philip NS. The future is now? rapid advances by brain stimulation innovation. Am J Psychiatry. 2020;177(8):654–656. PubMed CrossRef
  79. Cole EJ, Stimpson KH, Bentzley BS, et al. Stanford accelerated intelligent neuromodulation therapy for treatment-resistant depression. Am J Psychiatry. 2020;177(8):716–726. PubMed CrossRef
  80. FDA permits marketing of transcranial magnetic stimulation for treatment of obsessive-compulsive disorder. Accessed August 24, 2021. https://www.fda.gov/news-events/press-announcements/fda-permits-marketing-transcranial-magnetic-stimulation-treatment-obsessive-compulsive-disorder
  81. Jeffrey S. FDA approves first device to treat migraine pain. Accessed August 24, 2021.  https://www.medscape.com/viewarticle/817831

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