Acceptability, tolerability and safety of the BRIGhTMIND trial: Connectivity-guided intermittent theta-burst stimulation versus F3- repetitive transcranial magnetic stimulation for treatment-resistant depression.

Webster, Lucy; Boutry, Clement; Thomson, Louise; Abdelghani, Mohamed; Barber, Shaun; Briley, Paul M.; Kurkar, Micheal; Lankappa, Sudheer; McAllister-Williams, R. Hamish; Suazo Di Paola, Ana; Morriss, Richard

Abstract

Background

The BRIGhTMIND study was a double-blind RCT comparing repetitive transcranial magnetic stimulation at a standard simulation site (the “F3” location given by the International 10–20 system, F3-rTMS) versus connectivity-guided intermittent theta burst stimulation (cgiTBS) for treatment-resistant depression. This present study reports the acceptability, safety, and tolerability of F3-rTMS versus cgiTBS.

Methods

The present study used quantitative and qualitative methods. Two hundred fifty-four participants were included in the quantitative BRIGhTMIND acceptability and safety analysis (n = 126 F3-rTMS, n = 128 cgiTBS). Qualitative analysis included interviews for 15 participants (n = 7 F3-rTMS, n = 8 cgiTBS) and 582 written comments made by any participant randomised to the BRIGhTMIND trial regarding their experience of TMS and the study. Statistical analyses were used to explore differences between F3-rTMS and cgiTBS, as well as associations between acceptability, impression of change and safety. Qualitative data was analysed using an inductive thematic framework approach.

Outcomes

Acceptability, TMS benefits/negative effects and impression of improvement ratings did not differ across the two treatment protocols, with ratings maintained long-term (71.4 % rated TMS acceptable, 48.8 % indicated benefits of TMS outweighed negative effects and 52.2 % feeling somewhat or much better at 26 week follow-up n = 203). Impression of improvement was positively associated with acceptability and TMS benefits. Qualitative themes included participants' TMS experience, TMS response variability, and lay theories of effectiveness. Safety profiles were comparable between F3-rTMS and cgiTBS, with 74.5 % of participants (n = 190/254) experiencing at least one adverse event possibly, probably, or definitely related to TMS. The majority of adverse events were transient and mild, with a sizeable number requiring simple treatments or small adjustments to TMS intensity and coil positioning. The F3-rTMS group had a significantly greater proportion of participants that required small adjustments to TMS to tolerate treatment compared to the cgiTBS group. Serious adverse events were rare, with one serious event in each treatment arm possibly related to TMS (F3-rTMS- psychotic episode, cgiTBS-manic episode).

Conclusion

F3-rTMS and cgiTBS are comparably safe, tolerable and highly acceptable interventions for treatment-resistant depression. BRIGhTMIND systematically collected data from a large sample, providing evidence to meet the information needs of patients, clinicians and policy makers.

Citation

Webster, L., Boutry, C., Thomson, L., Abdelghani, M., Barber, S., Briley, P. M., Kurkar, M., Lankappa, S., McAllister-Williams, R. H., Suazo Di Paola, A., & Morriss, R. (2025). Acceptability, tolerability and safety of the BRIGhTMIND trial: Connectivity-guided intermittent theta-burst stimulation versus F3- repetitive transcranial magnetic stimulation for treatment-resistant depression. Comprehensive Psychiatry, 136, Article 152544. https://doi.org/10.1016/j.comppsych.2024.152544

• Journal Article Type: Article
• Acceptance Date: Oct 31, 2024
• Online Publication Date: Nov 4, 2024
• Publication Date: Jan 1, 2025
• Deposit Date: Feb 26, 2025
• Publicly Available Date: Feb 27, 2025
• Journal: Comprehensive psychiatry
• Print ISSN: 0010-440X
• Electronic ISSN: 1532-8384
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 136
• Article Number: 152544
• DOI: https://doi.org/10.1016/j.comppsych.2024.152544
• Public URL: https://nottingham-repository.worktribe.com/output/42755620
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S0010440X24000956?via%3Dihub
• PMID: 39504645
• Additional Information: This article is maintained by: Elsevier; Article Title: Acceptability, tolerability and safety of the BRIGhTMIND trial: Connectivity-guided intermittent theta-burst stimulation versus F3- repetitive transcranial magnetic stimulation for treatment-resistant depression; Journal Title: Comprehensive Psychiatry; CrossRef DOI link to publisher maintained version: https://doi.org/10.1016/j.comppsych.2024.152544; Content Type: article; Copyright: © 2024 Published by Elsevier Inc.