Application of Neuromodulation Techniques in Anxiety Treatment: A Systematic Review

AbstractIntroduction: Generalized Anxiety Disorder (GAD) is a prevalent mental health condition characterized by excessive worry and impaired emotion regulation. Traditional treatments, such as pharmacotherapy and cognitive behavioral therapy, may not be effective for all patients or can cause adverse effects. Non-Invasive Brain Stimulation (NIBS) techniques, including rTMS, tDCS, and tACS, have emerged as potential alternative treatments. This systematic review evaluates the effectiveness of these techniques in alleviating GAD symptoms. Methods: We followed the PRISMA guidelines to collect and analyze the data. A comprehensive literature search was conducted in PubMed, Web of Science, and Scopus databases until December 1, 2024. Studies were included if they involved adult participants diagnosed with GAD and examined the effects of multi-session NIBS interventions. A total of 14 studies were analyzed based on our inclusion criteria. Risk of bias was assessed using the Cochrane Collaboration tool. Results: rTMS was the most extensively studied modality, with high-frequency stimulation (10–20 Hz) over the right dorsolateral prefrontal cortex (dlPFC) demonstrating the most consistent anxiety reductions. Low-frequency rTMS (1 Hz) also showed efficacy in some studies. tDCS exhibited mixed results but appeared beneficial when combined with psychotherapy. A single study on tACS reported significant anxiety reductions, highlighting its potential as an emerging treatment. Dual-site stimulation and longer treatment protocols (≥20 sessions) yielded more sustained improvements. Conclusion: NIBS, particularly high-frequency rTMS over the right dlPFC, shows promise as a treatment for GAD. While tDCS and tACS present potential benefits, further research is needed to standardize stimulation parameters and optimize treatment efficacy. Future studies should focus on larger sample sizes, sham-controlled trials, and long-term follow-up to establish better clinical guidelines. Keywords: Generalized anxiety disorder, Anxiety, Transcranial direct current stimulation, Transcranial alternating current stimulation, and Repetitive transcranial magnetic stimulation