Faculty, Staff and Student Publications

Language

English

Publication Date

3-6-2026

Journal

Journal of Affective Disorders

DOI

10.1016/j.jad.2026.121553

PMID

41796776

Abstract

Background: Better-than-chance guessing of treatment assignment raises concerns about unblinding as this opens efficacy estimates up to being influenced by factors other than the true efficacy of the intervention. However, such accuracy does not necessarily indicate that efficacy estimates are biased.

Objective: To assess whether unblinding was biasing (impacting on efficacy estimates) or non-biasing (not impacting on efficacy estimates) in a sham-controlled trial of a home-use transcranial direct-current stimulation (tDCS) device, in which treatment allocation guesses at endpoint were unbalanced.

Methods: Interrelations between i) treatment allocation, ii) treatment allocation guesses, iii) adverse event reports, and iv) depressive symptom severity, as measured by Hamilton Depression Rating Scale, after ten weeks of treatment were examined using linear regression (n = 149).

Results: Receiving tDCS was positively associated with a) guessing that one had received tDCS (p = .01704), b) number of adverse events (beta: 0.69, p = .0046), and c) improvement after ten weeks (beta: -2.39, p = .0049). Guessing that one had received tDCS was positively associated with greater improvement (beta: -3.16, p = .0005), whereas the number of reported adverse events correlated negatively with improvement (beta: 0.68, p = .0186). Moreover, among participants who received tDCS, those who reported any of nine examined adverse events consistently showed numerically worse outcomes than those who did not report the same adverse events.

Conclusions: In this exploratory analysis, adverse events correlated negatively with HDRS-rated improvement. This is not consistent with a pathway where adverse events lead to unblinding and, subsequently, to improvement via expectancy effects and/or biased ratings.

Keywords

Depression, Meta-analysis, Neurostimulation, Transcranial direct-current stimulation, Unblinding, tDCS

Published Open-Access

yes

Download

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.