Comprehensive Mitigation of Peripheral and Central Stress Responses by Nx4: Insights From EEG and Heart Rate Variability in Post-Stress Resting State

Abstract

Objective: Stress from daily psychosocial challenges is a significant health concern with limited pharmacological treatment options. Psychosocial stress triggers distinct responses in the autonomic and central nervous systems, measurable via heart rate variability (HRV) and electroencephalogram (EEG). This post hoc analysis of clinical trial data explores the impact of the anti-stress medication Neurexan (Nx4) on HRV and EEG signals, and their correlation in a resting state following acute psychosocial stress induction. Methods: Data from the NEURIM trial (NCT02602275), a randomized, placebo-controlled, double-blind, cross-over study, were utilized. Participants received Nx4 before exposure to ScanSTRESS, a psychosocial stress paradigm. EEG and photoplethysmogram data were collected at rest before and after stress exposure. Stress responsivity under both placebo and Nx4 conditions was evaluated through HRV and EEG signals. Results: Psychosocial stress altered HRV parameters (increased LF/HF ratio, elevated Baevsky's Stress Index, reduced RMSSD) and EEG activity (decreased aperiodic offset, increased alpha power). Nx4 significantly mitigated stress-induced changes in LF/HF ratio, Baevsky's Stress Index, and aperiodic offset. A significant correlation was observed between Nx4 effects on HRV and EEG activity. Conclusion: Nx4 attenuates peripheral and central physiological stress responses, suggesting a comprehensive approach to mitigating stress responses in daily life. © 2025 The Author(s). Human Psychopharmacology: Clinical and Experimental published by John Wiley & Sons Ltd.