Combined Transcranial Direct Current Stimulation and Transcutaneous Cervical Vagus Nerve Stimulation for Anxiety and...

Anxiety and depressive disorders are among the leading causes of disability worldwide, yet current treatments remain limited by modest efficacy and restricted accessibility; non-invasive neuromodulation techniques such as transcranial direct current stimulation (tDCS) and transcutaneous cervical vagus nerve stimulation (tcVNS) have emerged as promising alternatives whose combination may produce complementary clinical effects. Methods: This proof-of-concept pilot study evaluated the feasibility, tolerability, and preliminary clinical effects of a multimodal three-component protocol comprising tDCS and tcVNS delivered alongside supportive psychological counseling in 12 adults (Mage = 54.75 ± 17.47 years) with clinically significant anxiety and depressive symptoms. Participants received 10 consecutive sessions of anodal tDCS over the left dorsolateral prefrontal cortex (2 mA, 30 min) followed by tcVNS with PEMF, with symptoms assessed using the Beck Anxiety Inventory (BAI) and Beck Depression Inventory (BDI) and pre-post comparisons performed via the Wilcoxon signed-rank test. Results: Significant reductions were observed for both outcomes: BAI scores decreased by 52.0% (Z = -3.059, p_exact < 0.001, p_asymp = 0.002, r = 0.883) and BDI scores by 55.9% (Z = -3.059, p_exact < 0.001, p_asymp = 0.002, r = 0.883); the proportion of participants in the minimal BDI-II symptom range rose from 8.3% to 83.3%, and no adverse events were reported. Standard clinical response rates (≥50% score reduction from baseline) were achieved by 50.0% of participants for depression (BDI) and 41.7% for anxiety (BAI), with 25.0% demonstrating a concurrent dual response on both measures. Exploratory profiling and multivariable continuous modeling indicated that higher cumulative improvement was descriptively observed in older participants with greater baseline symptom severity, with baseline anxiety showing the strongest continuous standardized association (β = 0.548, p = 0.104). These are hypothesis-generating observations only. Conclusions: The combined three-component package (tDCS, tcVNS, and concurrent supportive counseling) appears feasible, well tolerated, and associated with pre-post symptom reductions that, in the absence of a control condition, cannot be causally attributed to the intervention, warranting further investigation in adequately powered randomized sham-controlled trials.