A framework and practical guide for conducting double-blind randomized clinical trials combining transcranial electrical stimulation and psychotherapy

Abstract

Transcranial electrical stimulation (tES) is a non-invasive technique for modulating neural activity with minimal side effects, making it ideal for delivery concurrent with evidence-based psychotherapy. However, combining these modalities introduces unique methodological challenges that should be carefully addressed to ensure rigorous clinical trials with interpretable results. This article provides a conceptual guide and initial framework for designing and conducting double-blind randomized controlled trials that combine tES with evidence-based psychotherapy. We present a conceptual model for understanding the bidirectional influences between tES and evidence-based psychotherapy, outline critical considerations for study design, and provide practical guidelines for trial implementation. Drawing from recent clinical trials and established best practices, we also address key issues including target identification, blinding procedures, regulatory considerations, personnel requirements, and equipment needs. This guide is intended for investigators planning to conduct tES-psychotherapy studies and aims to enhance the quality and interpretability of research in this emerging field.