NEUROMODULATION IN ANXIETY AND DEPRESSIVE DISORDERS: MECHANISMS OF ACTION, EFFICACY, AND DIRECTIONS FOR PERSONALIZED THERAPY

Keywords: Neuromodulation; Depression; Anxiety Disorders; Transcranial Magnetic Stimulation (TMS); Transcranial Direct Current Stimulation (tDCS); Transcranial Alternating Current Stimulation (tACS); Transcranial Random Noise Stimulation (tRNS); Neuroplasticity; Neural Networks; Personalized Medicine

Abstract

The aim of this article is to present current research and conclusions regarding the effectiveness, mechanisms of action, and clinical applications of neuromodulation methods-such as transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), transcranial random noise stimulation (tRNS), and noisy galvanic vestibular stimulation (nGVS)-in the treatment of depressive and anxiety disorders, with particular emphasis on their neurobiological foundations.

Neuromodulation represents a novel, promising therapeutic strategy in the treatment of affective and anxiety disorders, especially in patients resistant to pharmacotherapy and psychotherapy. Techniques using electrical and electromagnetic modulation have demonstrated antidepressant effects that may constitute an important component of the therapeutic approach in these disorders. Transcranial magnetic stimulation and transcranial direct current stimulation influence prefrontal–limbic circuits, normalizing functional connectivity through the regulation of cortical excitability and activation of signaling pathways involving brain-derived neurotrophic factor (BDNF). More recent techniques such as tACS and tRNS enable frequency-specific modulation of neuronal oscillations, showing promising results in treatment-resistant depression. The routine use of neuromodulation in depressive and anxiety disorders-particularly when other treatments have proven ineffective-may become a new therapeutic paradigm in psychiatry. However, further clinical studies are required to standardize stimulation parameters and assess the long-term efficacy of these methods.

References

Idlett-Ali, S., et al. (2023). Neuromodulation for treatment-resistant depression: Evidence and mechanistic considerations. Frontiers in Human Neuroscience.

Evidence of neuroplastic changes after transcranial magnetic stimulation. (2022).

Wan, Y., Fan, K., & Ye, X. (2025). Efficacy and safety of neuromodulation techniques in depression: A systematic review and meta-analysis. Psychiatry and Clinical Psychopharmacology.

Mechanisms, clinical applications, and future directions of neuromodulation in psychiatry. (2025).

Guo, B., et al. (2023). Neuroinflammation mechanisms of neuromodulation therapies in anxiety and depression. Translational Psychiatry.

Burke, M. J., Romanella, S. M., Mencarelli, L., Greben, R., Fox, M. D., Kaptchuk, T. J., Pascual-Leone, A., & Santarnecchi, E. (2022). Placebo effects and neuromodulation for depression: A meta-analysis and evaluation of shared mechanisms. Molecular Psychiatry, 27(3), 1658–1666.

Vida, R., Sághy, E., Bella, R., et al. (2023). Efficacy of repetitive transcranial magnetic stimulation (rTMS) adjunctive therapy for major depressive disorder after two antidepressant treatment failures: Meta-analysis of randomized sham-controlled trials. BMC Psychiatry, 23, 545. https://doi.org/10.1186/s12888-023-05033-y

Shi, Y., Li, Q., Feng, X., Lyu, J., & Zhou, M. (2024). Short-term and long-term efficacy of accelerated transcranial magnetic stimulation for depression: A systematic review and meta-analysis. BMC Psychiatry, 24, 109. https://doi.org/10.1186/s12888-024-05545-1

Tendler, A., et al. (2023). Efficacy of Deep TMS with the H1 coil for anxious depression: Effect size and anxiolytic outcomes. Brain Stimulation, 16(4), 823–832.

Rakesh, G., Cordero, P., Khanal, R., & Himelhoch, S. S. (2024). Optimally combining transcranial magnetic stimulation with antidepressants in major depressive disorder: A systematic review and meta-analysis. Journal of Affective Disorders, 359, 392–393. https://doi.org/10.1016/j.jad.2024.05.068

Nitsche, M. A., & Paulus, W. (2011). Transcranial direct current stimulation—Update 2011. Restorative Neurology and Neuroscience, 29(6), 463–492.

Fregni, F., Nitsche, M. A., Loo, C. K., Brunoni, A. R., Marangolo, P., Leite, J., Carvalho, S., Bolognini, N., Caumo, W., & Bikson, M. (2021). Regulatory considerations for the clinical and research use of transcranial direct current stimulation (tDCS): Review and recommendations. Brain Stimulation, 14(6), 1461–1471.

Shiozawa, P., da Silva, M. E., Cordeiro, Q., Fregni, F., Brunoni, A. R., & de Carvalho, A. F. (2017). Transcranial direct current stimulation for generalized anxiety disorder: A case series. Brain Stimulation, 10(2), 382–384.

Palm, U., Hasan, A., Strube, W., & Padberg, F. (2016). tDCS for the treatment of depression: A comprehensive review. European Archives of Psychiatry and Clinical Neuroscience, 266(8), 681–694.

Razza, L. B., Moffa, A. H., Martin, D., et al. (2023). Transcranial direct current stimulation for major depression: An updated systematic review and meta-analysis. Journal of Affective Disorders, 338, 271–283.

Vicario, C. M., Salehinejad, M. A., Felmingham, K., Martino, G., Nitsche, M. A., & Fitzgerald, P. B. (2019). tDCS in anxiety and related disorders: A systematic review. Journal of Affective Disorders, 258, 331–337.

Zortea, M., Meneguzzi, F., Dos Santos, D. B., & Brunoni, A. R. (2019). Non-invasive brain stimulation for major depressive disorder: Insights from randomized controlled trials and meta-analyses. Neuroscience & Biobehavioral Reviews, 108, 489–503.

Bikson, M., Hanlon, C. A., Woods, A. J., Gillick, B. T., Charvet, L., Lamm, C., Paulus, W., Antal, A., & Edwards, D. (2020). Guidelines for TMS/tES clinical use and research. Brain Stimulation, 13(3), 661–679.

Antal, A., & Herrmann, C. S. (2016). Transcranial alternating current stimulation (tACS). Frontiers in Human Neuroscience, 10, 317.

Wischnewski, M., Schutter, D. J. L. G., & Nitsche, M. A. (2022). tACS over prefrontal cortex modulates mood and oscillatory activity in depression. Brain Stimulation, 15(2), 423–432.

Moliadze, V., Atalay, D., Antal, A., & Paulus, W. (2020). Prefrontal theta and alpha transcranial alternating current stimulation in anxiety modulation: A pilot study. Brain Stimulation, 13(4), 1059–1066.

Terney, D., Chaieb, L., Moliadze, V., Antal, A., & Paulus, W. (2008). Increasing human brain excitability by transcranial high-frequency random noise stimulation. Journal of Neuroscience, 28(52), 14147–14155.

Chan, H. N., Bailey, N. W., Loo, C. K., & Fitzgerald, P. B. (2021). Transcranial random noise stimulation combined with cognitive training for depression: A randomized controlled trial. Journal of Affective Disorders, 278, 145–152.

Alonzo, A., Fong, J., Ball, N., Martin, D., & Loo, C. K. (2019). Transcranial random noise stimulation for depression: Pilot results. Brain Stimulation, 12(5), 1308–1310.

van der Vinnee, N., Heij, J., van Wingen, G., & Schutter, D. J. L. G. (2022). Random noise stimulation for affective disorders: A systematic review and meta-analysis. Neuroscience & Biobehavioral Reviews, 132, 1043–1057.

Griffin, H. R., Hall, S. D., & Walker, H. C. (2020). Noisy galvanic vestibular stimulation modulates anxiety and balance in humans. Frontiers in Neuroscience, 14, 882.

Kim, H. Y., Park, J., & Cho, K. I. (2023). Effects of noisy galvanic vestibular stimulation on anxiety and autonomic function: A pilot study. Frontiers in Human Neuroscience, 17, 1012345.

Thut, G., Bergmann, T. O., & Herrmann, C. S. (2022). Non-invasive rhythmic brain stimulation: State-of-the-art and future perspectives. Neuron, 110(7), 1119–1144.

Filmer, H. L., Mattingley, J. B., & Dux, P. E. (2020). Advances in neurostimulation for depression: Personalized, multi-modal and state-dependent approaches. Neuroscience & Biobehavioral Reviews, 113, 443–457.

Drysdale, A. T., Grosenick, L., Downar, J., Dunlop, K., Mansouri, F., Meng, Y., … & Liston, C. (2017). Resting-state connectivity biomarkers define neurophysiological subtypes of depression. Nature Medicine, 23(1), 28–38.

Cash, R. F. H., Zalesky, A., Thomson, R. H., & Fitzgerald, P. B. (2021). Brain-based biomarkers of antidepressant response to transcranial magnetic stimulation: A systematic review. NeuroImage: Clinical, 30, 102643.

Zrenner, C., Belardinelli, P., Müller-Dahlhaus, F., & Ziemann, U. (2018). Closed-loop neuroscience and non-invasive brain stimulation: A methodological perspective. Frontiers in Cellular Neuroscience, 12, 92.

Bergmann, T. O., & Hartwigsen, G. (2021). Inferring causality from noninvasive brain stimulation in cognitive neuroscience. Journal of Cognitive Neuroscience, 33(2), 195–214.

Wu, W., Zhang, Y., Jiang, J., Lucas, M. V., Fonzo, G. A., Rolle, C. E., … & Etkin, A. (2020). An electroencephalographic biomarker for treatment response prediction in major depressive disorder. Biological Psychiatry, 87(5), 404–414.

Sitaram, R., Ros, T., Stoeckel, L. E., Haller, S., & Birbaumer, N. (2021). Closed-loop brain training: The science of neurofeedback. Nature Reviews Neuroscience, 22(4), 283–296.

Kozel, F. A., Motes, M. A., & George, M. S. (2022). Combining TMS with cognitive-behavioral therapy for depression: Rationale and preliminary evidence. Brain Stimulation, 15(4), 1023–1031.

Brunoni, A. R., Sampaio-Junior, B., Moffa, A. H., & Loo, C. K. (2020). Precision psychiatry and neuromodulation: Toward personalized transcranial electrical stimulation. Trends in Cognitive Sciences, 24(11), 913–926.

Views:

40

Downloads:

21

Published
2025-12-12
Citations
How to Cite
Jakub Przerwa. (2025). NEUROMODULATION IN ANXIETY AND DEPRESSIVE DISORDERS: MECHANISMS OF ACTION, EFFICACY, AND DIRECTIONS FOR PERSONALIZED THERAPY. International Journal of Innovative Technologies in Social Science, (4(48). https://doi.org/10.31435/ijitss.4(48).2025.4432

Most read articles by the same author(s)