As early as the 1990s, researchers first suggested that rTMS may be able to improve MDD through modulating aberrant brain activity associated with MDD.¹,² In particular, there is reduced activity in the left dorsolateral prefrontal cortex (DLPFC) and relatively increased activity in the right DLPFC.3,4,5 These areas are highly involved in cognitive activities and the regulation of deeper brain regions involved in emotional processes.5 Asymmetry of prefrontal brain activity has been shown to correlate with the severity of certain symptoms of depression6, and may be normalized following successful antidepressant treatment7.
Many studies have investigated different rTMS protocols for the treatment of depression.8 However, most have focused on high-frequency (excitatory) stimulation of the left DLPFC.5 Imaging studies have revealed that the antidepressant benefits of this application are associated with modulation of both local and distant brain region activity, and neural network connectivity.9,10,11,12,13
Horizon TMS Therapy Systems are indicated for the treatment of major depressive disorder (MDD) in adult patients who have failed to achieve satisfactory improvement from prior antidepressant medication in the current episode. These systems are FDA cleared for standard treatment at 10Hz (19 minutes and 37.5 minutes protocols), and for intermittent theta burst stimulation (iTBS; 3 minutes protocol).
The majority of rTMS research has been conducted on patients who have failed on at least two or three adequate trials of antidepressants within their current episode.14 These patients are often referred to as being treatment-resistant, with only around 13% of these patients achieving remission with a fourth-line medication.15 In patients with this level of treatment-resistance, high-frequency (10Hz) stimulation to the left dorsolateral prefrontal cortex (DLPFC) has been shown to lead to around half (57%) of patients achieving a clinical response, and around a third (37%) of patients achieving remission.16
More recently, another excitatory left DLPFC protocol, called intermittent theta burst stimulation (iTBS), has been investigated as an application in treatment resistant MDD (TR-MDD). This brief protocol takes just over 3 minutes to deliver and in patients with TR-MDD, iTBS was non-inferior to 10 Hz rTMS for the treatment of depression.17
¹Höflich, G., Kasper, S., Hufnagel, A., Ruhrmann, S., & Möller, H. J. (1993). Application of transcranial magnetic stimulation in treatment of drug‐resistant major depression—a report of two cases. Human Psychopharmacology: Clinical and Experimental, 8(5), 361-365.
²George, M. S., Wassermann, E. M., Williams, W. A., Callahan, A., Ketter, T. A., Basser, P., … & Post, R. M. (1995). Daily repetitive transcranial magnetic stimulation (rTMS) improves mood in depression. Neuroreport: An International Journal for the Rapid Communication of Research in Neuroscience.
³Henriques, J. B., & Davidson, R. J. (1991). Left frontal hypoactivation in depression. Journal of abnormal psychology, 100(4), 535.
4 Levin, R.L., Heller, W., Mohanty, A. et al. Cognitive Deficits in Depression and Functional Specificity of Regional Brain Activity. Cogn Ther Res 31, 211–233 (2007).
5De Raedt, R., Vanderhasselt, M. A., & Baeken, C. (2015). Neurostimulation as an intervention for treatment resistant depression: From research on mechanisms towards targeted neurocognitive strategies. Clinical Psychology Review, 41, 61-69.
6Gollan, J. K., Hoxha, D., Chihade, D., Pflieger, M. E., Rosebrock, L., & Cacioppo, J. (2014). Frontal alpha EEG asymmetry before and after behavioral activation treatment for depression. Biological psychology, 99, 198-208.
7Martinot, J. L., Hardy, P., Feline, A., Huret, J. D., Mazoyer, B., Attar-Levy, D., … & Syrota, A. (1990). Left prefrontal glucose hypometabolism in the depressed state: a confirmation. The American journal of psychiatry.
8 Brunoni, A. R., Chaimani, A., Moffa, A. H., Razza, L. B., Gattaz, W. F., Daskalakis, Z. J., & Carvalho, A. F. (2017). Repetitive transcranial magnetic stimulation for the acute treatment of major depressive episodes: a systematic review with network meta-analysis. JAMA psychiatry, 74(2), 143-152.
9 Teneback, C. C., Nahas, Z., Speer, A. M., Molloy, M., Stallings, L. E., Spicer, K. M., … & George, M. S. (1999). Changes in prefrontal cortex and paralimbic activity in depression following two weeks of daily left prefrontal TMS. The Journal of neuropsychiatry and clinical neurosciences, 11(4), 426-435.
10Kito, S., Fujita, K., & Koga, Y. (2008). Regional cerebral blood flow changes after low-frequency transcranial magnetic stimulation of the right dorsolateral prefrontal cortex in treatment-resistant depression. Neuropsychobiology, 58(1), 29-36.
11Luborzewski, A., Schubert, F., Seifert, F., Danker-Hopfe, H., Brakemeier, E. L., Schlattmann, P., … & Bajbouj, M. (2007). Metabolic alterations in the dorsolateral prefrontal cortex after treatment with high-frequency repetitive transcranial magnetic stimulation in patients with unipolar major depression. Journal of psychiatric research, 41(7), 606-615.
12Anderson, R. J., Hoy, K. E., Daskalakis, Z. J., & Fitzgerald, P. B. (2016). Repetitive transcranial magnetic stimulation for treatment resistant depression: Re-establishing connections. Clinical Neurophysiology, 127(11), 3394-3405.
13Philip, N. S., Barredo, J., Aiken, E., & Carpenter, L. L. (2018). Neuroimaging mechanisms of therapeutic transcranial magnetic stimulation for major depressive disorder. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, 3(3), 211-222.
14Kiebs, M., Hurlemann, R., & Mutz, J. (2019). Repetitive transcranial magnetic stimulation in non-treatment-resistant depression. The British Journal of Psychiatry, 215(2), 445-446.
15Warden, D., Rush, A. J., Trivedi, M. H., Fava, M., & Wisniewski, S. R. (2007). The STAR* D Project results: a comprehensive review of findings. Current psychiatry reports, 9(6), 449-459.
16Carpenter, L. L., Janicak, P. G., Aaronson, S. T., Boyadjis, T., Brock, D. G., Cook, I. A., … & Demitrack, M. A. (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.
17Blumberger, D. M., Vila-Rodriguez, F., Thorpe, K. E., Feffer, K., Noda, Y., Giacobbe, P., … & Downar, J. (2018). Effectiveness of theta burst versus high-frequency repetitive transcranial magnetic stimulation in patients with depression (THREE-D): a randomised non-inferiority trial. The Lancet, 391(10131), 1683-1692.