Rishi Ramesh

Background: Of all diagnosed Major Depressive Disorder, roughly 30% is treatment resistant. This means that multiple courses of pharmaceutical treatments have failed for a patient, and there may not be any options of treatment with high success rates left.^{1, 2} Transcranial Magnetic Stimulation Therapy has been discussed as a potential opportunity to treat treatment resistant depression (TRD), but its effects, targets, and use cases have not been properly outlined. Through the blinded, sham-controlled testing, targeting multiple regions of the brain, and fMRI studies discussed in this paper, we’re able to see the current understanding of rTMS for TRD and what the treatment has uncovered about TRD.^{3, 4, 5}

Objective: In this narrative review, I described the mechanisms and effects of transcranial magnetic stimulation on treatment resistant depression.

Search Methods: An online search in the PubMed database for sources between the years of 2017 and 2023 using the keywords: “transcranial magnetic stimulation”, “treatment resistant depression”, and looking into sources cited by these results.

Results: rTMS shows that a key predictor of treatment success is the interconnectivity of brain regions. This in particular is a factor in diagnosing and treating depression that has as of yet not been studied intently. The studies show that there is a connection between how connected certain regions of the brain are including the dorsolateral prefrontal cortex, subgenual anterior cingulate cortex, and more. Further research will identify the connection between these interconnections and major depressive disorder that is not treatment-resistant.

Conclusions: Studies have found that the interconnectedness of the dorsolateral prefrontal cortex and subgenual anterior cingulate cortex and certain other regions of the brain can predict if transcranial magnetic stimulation will have an effect on treatment-resistant depression. The response to repetitive transcranial magnetic stimulation may also be specific to treatment resistant depression, indicating that there are differences in pathology.^6,7,8

Works Cited:

1. Gálvez JF, Keser Z, Mwangi B, et al. The medial forebrain bundle as a deep brain stimulation target for treatment resistant depression: A review of published data. Prog Neuropsychopharmacol Biol Psychiatry. 2015;58:59-70. doi:10.1016/j.pnpbp.2014.12.003
2. Dandekar MP, Fenoy AJ, Carvalho AF, Soares JC, Quevedo J. Deep brain stimulation for treatment-resistant depression: an integrative review of preclinical and clinical findings and translational implications. Mol Psychiatry. 2018;23(5):1094-1112. doi:10.1038/mp.2018.2
3. Fava M. Diagnosis and definition of treatment-resistant depression. Biol Psychiatry. 2003;53(8):649-659. doi:10.1016/s0006-3223(03)00231-2
4. Kaster TS, Daskalakis ZJ, Noda Y, et al. Efficacy, tolerability, and cognitive effects of deep transcranial magnetic stimulation for late-life depression: a prospective randomized controlled trial. Neuropsychopharmacology. 2018;43(11):2231-2238. doi:10.1038/s41386-018-0121-x
5. Nestor SM, Mir-Moghtadaei A, Vila-Rodriguez F, et al. Large-scale structural network change correlates with clinical response to rTMS in depression. Neuropsychopharmacology. 2022;47(5):1096-1105. doi:10.1038/s41386-021-01256-3
6. Ge R, Downar J, Blumberger DM, Daskalakis ZJ, Vila-Rodriguez F. Functional connectivity of the anterior cingulate cortex predicts treatment outcome for rTMS in treatment-resistant depression at 3-month follow-up. Brain Stimul. 2020;13(1):206-214. doi:10.1016/j.brs.2019.10.012
7. Weigand A, Horn A, Caballero R, et al. Prospective Validation That Subgenual Connectivity Predicts Antidepressant Efficacy of Transcranial Magnetic Stimulation Sites. Biol Psychiatry. 2018;84(1):28-37. doi:10.1016/j.biopsych.2017.10.028
8. Benschop, L., Vanhollebeke, G., Li, J. et al. Reduced subgenual cingulate–dorsolateral prefrontal connectivity as an electrophysiological marker for depression. Sci Rep 12, 16903 (2022). https://doi.org/10.1038/s41598-022-20274-9