Transcranial alternating current stimulation (tACS) at 77.5 Hz and 15 mA, targeting the forehead and mastoid areas, has proven efficacious in patients with major depressive disorder (MDD) by simultaneously stimulating multiple brain nuclei and regions, many of which are critical for blood pressure regulation. This post hoc analysis aimed to assess the potential blood pressure-lowering effects of 77.5 Hz, 15 mA tACS in first-episode drug-naive MDD patients with normotension.Data from a previous randomized controlled trial (RCT) involving first-episode drug-naive MDD patients were analyzed. Participants underwent 20 sessions of either active tACS or sham stimulation. Vital signs, including systolic blood pressure (SBP) and diastolic blood pressure (DBP), were measured at baseline, after treatment (Week 4), and at follow-up (Week 8). Multivariate linear regression and Generalized Estimating Equations (GEE) models were used to evaluate the effects of the treatment on blood pressure.Totally 68 participants were analysis (33 in the sham group and 35 in the active group). By Week 4, the active tACS group exhibited a significant reduction in both SBP and DBP compared to the sham group (coefficient - 2.04, 95 % CI -3.01 to -1.07, p < 0.001 on SBP, and coefficient - 1.92, 95 % CI -2.69 to -1.18, p < 0.001 on DBP).tACS at 77.5 Hz and 15 mA can effectively reduce SBP and DBP in first-episode drug-naive depressive individuals with normotension, with greater reductions observed in those with higher baseline levels.Copyright © 2025 Elsevier B.V. All rights reserved.