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Connectivity-guided intermittent theta burst versus repetitive transcranial magnetic stimulation for treatment-resistant depression: a randomized controlled trial

Lookup NU author(s): Professor Hamish McAllister-WilliamsORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2024, The Author(s).Disruption in reciprocal connectivity between the right anterior insula and the left dorsolateral prefrontal cortex is associated with depression and may be a target for neuromodulation. In a five-center, parallel, double-blind, randomized controlled trial we personalized resting-state functional magnetic resonance imaging neuronavigated connectivity-guided intermittent theta burst stimulation (cgiTBS) at a site based on effective connectivity from the right anterior insula to the left dorsolateral prefrontal cortex. We tested its efficacy in reducing the primary outcome depression symptoms measured by the GRID Hamilton Depression Rating Scale 17-item over 8, 16 and 26 weeks, compared with structural magnetic resonance imaging (MRI) neuronavigated repetitive transcranial magnetic stimulation (rTMS) delivered at the standard stimulation site (F3) in patients with ‘treatment-resistant depression’. Participants were randomly assigned to 20 sessions over 4–6 weeks of either cgiTBS (n = 128) or rTMS (n = 127) with resting-state functional MRI at baseline and 16 weeks. Persistent decreases in depressive symptoms were seen over 26 weeks, with no differences between arms on the primary outcome GRID Hamilton Depression Rating Scale 17-item score (intention-to-treat adjusted mean, −0.31, 95% confidence interval (CI) −1.87, 1.24, P = 0.689). Two serious adverse events were possibly related to TMS (mania and psychosis). MRI-neuronavigated cgiTBS and rTMS were equally effective in patients with treatment-resistant depression over 26 weeks (trial registration no. ISRCTN19674644).

Publication metadata

Author(s): Morriss R, Briley PM, Webster L, Abdelghani M, Barber S, Bates P, Brookes C, Hall B, Ingram L, Kurkar M, Lankappa S, Liddle PF, McAllister-Williams RH, O'Neil-Kerr A, Pszczolkowski S, Suazo Di Paola A, Walters Y, Auer DP

Publication type: Article

Publication status: Published

Journal: Nature Medicine

Year: 2024

Volume: 30

Pages: 403-413

Print publication date: 01/02/2024

Online publication date: 16/01/2024

Acceptance date: 12/12/2023

Date deposited: 20/02/2024

ISSN (print): 1078-8956

ISSN (electronic): 1546-170X

Publisher: Nature Research


DOI: 10.1038/s41591-023-02764-z


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Funder referenceFunder name
a MRC and National Institute for Health and Care Research (NIHR) partnership
the Efficacy and Mechanism Evaluation program (16/44/02)