TMS Research

Transcranial Magnetic Stimulation (TMS) is a non-invasive method used to stimulate targeted regions of the brain and has become increasingly significant in treating depression, including anxious depression. The research in this field is vast and continually evolving. 

Below is a list of seminal and influential articles that have contributed to our understanding and application of TMS for depression and anxious depression. The selection includes foundational studies, reviews, and meta-analyses that have shaped clinical practices and guidelines.

Foundational Studies and Reviews

Barker, A.T., Jalinous, R., Freeston, I.L. (1985). Non-invasive magnetic stimulation of human motor cortex. The Lancet, 325(8437), 1106-1107.

  • This is the seminal study that first demonstrated the principle of non-invasive magnetic stimulation of the human motor cortex, laying the groundwork for the development of TMS.

Berman, R.M., Narasimhan, M., Sanacora, G., et al. (2000). A randomized clinical trial of repetitive transcranial magnetic stimulation in the treatment of major depression. Biological Psychiatry, 47(4), 332-337.

Carpenter, L.L., Janicak, P.G., Aaronson, S.T., et al. (2012). Transcranial magnetic stimulation (TMS) for major depression: A multisite, naturalistic, observational study of acute treatment outcomes in clinical practice. Depression and Anxiety, 29(7), 587-596. 

  • This observational study offers real-world insights into the effectiveness of TMS in clinical settings, highlighting its potential benefits for treatment-resistant depression.

George, M.S., Lisanby, S.H., Avery, D., et al. (2010). Daily left prefrontal transcranial magnetic stimulation therapy for major depressive disorder: A sham-controlled randomized trial. Archives of General Psychiatry, 67(5), 507-516. 

  • This study is one of the pivotal trials that supported the efficacy of TMS in treating major depressive disorder (MDD), providing a basis for its approval by regulatory agencies.

George, M.S., Wassermann, E.M., Williams, W.A., et al. (1995). Daily repetitive transcranial magnetic stimulation (rTMS) improves mood in depression. Neuroreport, 6(14), 1853-1856.

  • This study was among the first to report improvements in mood in patients with depression following daily rTMS sessions, suggesting its therapeutic potential.

Klein, E., Kreinin, I., Chistyakov, A., et al. (1999). Therapeutic efficacy of right prefrontal slow repetitive transcranial magnetic stimulation in major depression: A double-blind controlled study. Archives of General Psychiatry, 56(4), 315-320.

  • A key double-blind controlled study that demonstrated the therapeutic efficacy of rTMS applied to the right prefrontal cortex in patients with major depression.

O’Reardon, J.P., Solvason, H.B., Janicak, P.G., et al. (2007). Efficacy and safety of transcranial magnetic stimulation in the acute treatment of major depression: A multisite randomized controlled trial. Biological Psychiatry, 62(11), 1208-1216. 

  • A significant multisite study demonstrating the efficacy and safety of TMS in treating major depression.

Pascual-Leone, A., Rubio, B., Pallardó, F., Catalá, M.D. (1996). Rapid-rate transcranial magnetic stimulation of left dorsolateral prefrontal cortex in drug-resistant depression. The Lancet, 348(9022), 233-237.

  • An early study that showed the potential of rapid-rate TMS in treating drug-resistant depression, focusing on the left dorsolateral prefrontal cortex.

Meta-Analyses

Berlim, M.T., Van den Eynde, F., & Daskalakis, Z.J. (2013). Efficacy and acceptability of high frequency repetitive transcranial magnetic stimulation (rTMS) versus electroconvulsive therapy (ECT) for major depression: A systematic review and meta-analysis of randomized trials. Depression and Anxiety, 30(7), 614-623. 

  • A comprehensive meta-analysis comparing the efficacy and acceptability of TMS versus ECT in the treatment of major depression.

Gaynes, B.N., Lloyd, S.W., Lux, L., et al. (2014). Repetitive transcranial magnetic stimulation for treatment-resistant depression: A systematic review and meta-analysis. Journal of Clinical Psychiatry, 75(5), 477-489. 

  • This systematic review and meta-analysis focus on the use of TMS for treatment-resistant depression, underscoring its role in managing difficult-to-treat cases.

Studies on Anxious Depression

Baeken, C., Marinazzo, D., Everaert, H., et al. (2015). Specific cognitive-neural patterns predict emotion regulation success in major depressive disorder. Psychiatry Research: Neuroimaging, 234(3), 328-335.

  • Investigates the neural mechanisms of emotion regulation in depression, providing insights into how TMS may modulate these pathways in patients with anxious depression.

Carpenter, L.L., Moreno, F.A., Kling, M.A., et al. (2012). Safety and efficacy of rTMS in the treatment of major depression: A critical review. Clinical Neurophysiology, 123(5), 960-973. 

  • Reviews the safety and efficacy of rTMS in treating major depression, with implications for its use in anxious depression.

Recent Advances and Perspectives

Cole, E.J., Stimpson, K.H., Bentzley, B.S., et al. (2020). Stanford Accelerated Intelligent Neuromodulation Therapy for Treatment-Resistant Depression. American Journal of Psychiatry, 177(8), 716-726.

  • This article provides a detailed overview of the SAINT protocol, demonstrating its efficacy in rapidly reducing symptoms of treatment-resistant depression, with the majority of patients achieving remission.

Dunner, D.L., Aaronson, S.T., Sackeim, H.A., et al. (2014). A multisite, naturalistic, observational study of transcranial magnetic stimulation for patients with pharmacoresistant major depressive disorder: Durability of benefit over a 1-year follow-up period. Journal of Clinical Psychiatry, 75(12), 1394-1401. 

  • This study assesses the long-term benefits of TMS in patients with treatment-resistant major depressive disorder, relevant for considering the durability of treatment effects in anxious depression.

Fox, M.D., Buckner, R.L., White, M.P., Greicius, M.D., Pascual-Leone, A. (2012). Efficacy of Transcranial Magnetic Stimulation Targets for Depression Is Related to Intrinsic Functional Connectivity with the Subgenual Cingulate. Biological Psychiatry, 72(7), 595-603.

  • This landmark study established a connection between the efficacy of TMS targets for depression and their functional connectivity with the subgenual cingulate, laying the groundwork for personalized TMS targeting strategies like cardio-neuro-navigation.

Philip, N.S., Barredo, J., van ‘t Wout-Frank, M., et al. (2019). Network mechanisms of clinical response to transcranial magnetic stimulation in posttraumatic stress disorder and major depressive disorder. Biological Psychiatry, 85(4), 283-292. 

  • Explores the neural network changes associated with TMS treatment in PTSD and major depressive disorder, offering perspectives on its efficacy in comorbid anxiety and depression.

Weigand, A., Horn, A., Caballero, R., Cooke, D., Stern, A.P., Taylor, S.F., Fox, M.D. (2018). Prospective Validation that Subgenual Connectivity Predicts Antidepressant Efficacy of Transcranial Magnetic Stimulation Sites. Biological Psychiatry, 84(1), 28-37.

  • This research further supports the use of functional connectivity as a guide for targeting TMS, showing that connectivity with the subgenual cingulate predicts the antidepressant efficacy of TMS.

Williams, N.R., Sudheimer, K.D., Bentzley, B.S., et al. (2018). High-dose, fast-frequency, not low-dose, slow-frequency rTMS reduces suicide ideation in refractory depression. Brain Stimulation, 11(2), 337-345.

  • This study highlights the potential of high-dose, fast-frequency rTMS protocols like SAINT in reducing suicidal ideation among patients with refractory depression, marking a significant shift from traditional TMS approaches.
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