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

Morriss, Richard; Briley, Paul M.; Webster, Lucy; Abdelghani, Mohamed; Barber, Shaun; Bates, Peter; Brookes, Cassandra; Hall, Beth; Ingram, Luke; Kurkar, Micheal; Lankappa, Sudheer; Liddle, Peter F.; McAllister-Williams, R. Hamish; O’Neil-Kerr, Alexander; Pszczolkowski, Stefan; Suazo Di Paola, Ana; Walters, Yvette; Auer, Dorothee P.

Abstract

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).

Citation

Morriss, R., Briley, P. M., Webster, L., Abdelghani, M., Barber, S., Bates, P., Brookes, C., Hall, B., Ingram, L., Kurkar, M., Lankappa, S., Liddle, P. F., McAllister-Williams, R. H., O’Neil-Kerr, A., Pszczolkowski, S., Suazo Di Paola, A., Walters, Y., & Auer, D. P. (2024). Connectivity-guided intermittent theta burst versus repetitive transcranial magnetic stimulation for treatment-resistant depression: a randomized controlled trial. Nature Medicine, 30(2), 403–413. https://doi.org/10.1038/s41591-023-02764-z

• Journal Article Type: Article
• Acceptance Date: Dec 12, 2023
• Online Publication Date: Jan 16, 2024
• Publication Date: 2024-02
• Deposit Date: Apr 15, 2024
• Publicly Available Date: Apr 15, 2024
• Journal: Nature Medicine
• Print ISSN: 1078-8956
• Electronic ISSN: 1546-170X
• Publisher: Nature Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 30
• Issue: 2
• Pages: 403–413
• DOI: https://doi.org/10.1038/s41591-023-02764-z
• Keywords: Depression; Magnetic resonance imaging; Outcomes research
• Public URL: https://nottingham-repository.worktribe.com/output/29841445
• Publisher URL: https://www.nature.com/articles/s41591-023-02764-z
• Additional Information: Received: 29 June 2023; Accepted: 12 December 2023; First Online: 16 January 2024; : R.M. has received funding for research from Electromedical Products, Inc. and fees for participation in a Data Monitoring Ethics Committee for two trials in depression from Novartis plc. M.A. has received fees for consulting and giving lectures by Takeda Pharmaceutical, Janssen Pharmaceutical and the Clinical TMS Society. R.H.M.-W. declares fees for consulting and giving lectures from Janssen-Cilag, LivaNova, Lundbeck, P1Vital, Sage Therapeutics, Sothema and Takeda. No other potential conflicts of interest are reported for any of the other authors. No third parties have been involved in the study design, analysis and writing of the manuscript.