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Effects of transcranial magnetic stimulation of the rostromedial prefrontal cortex in obsessive–compulsive disorder: a randomized clinical trial

Nature Mental Health volume 1, pages 555–563 (2023)Cite this article

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Abstract

New interventions are needed for obsessive-compulsive disorder. Here we present a randomized single-blinded, two-arm, parallel-group, sham-controlled clinical trial assessing the efficacy of prefrontal cortex stimulation in reducing obsessive-compulsive disorder symptoms and frontostriatal connectivity (ACTRN12616001687482). Conducted at a single academic center, the trial enrolled participants diagnosed with obsessive-compulsive disorder who underwent baseline clinical assessments and neuroimaging. The intervention comprised 20 weekday sessions of neuronavigated continuous theta burst stimulation of the frontal pole or sham. Participants and all staff assessing intervention outcomes were blind to the conditions. We enrolled a sample of 50 individuals (26 active continuous theta burst stimulation) who completed the neuroimaging and clinical assessments at the primary 4 week endpoint. Clinical data at the secondary 6 month endpoint were obtained from 46 participants (23 active). Symptoms of obsessive-compulsive disorder (primary outcome) decreased in both groups (active −4.35, P < 0.001; sham −5.92, P < 0.001), but there was no significant difference between groups (P = 0.33, ηp2 = 0.02). Likewise, there was no significant difference between groups in changes of frontal pole connectivity with the striatum (P = 0.09, ηp2 = 0.06). Changes in secondary outcomes (symptoms of anxiety and depression and localized frontal pole activity) did not differ between groups. Dropout rates did not vary between groups and the most common treatment-related adverse event in both groups was headache. Our findings suggest that frontal pole continuous theta burst stimulation is no different to sham in reducing obsessive-compulsive disorder symptoms. The absence of changes in brain activity prompts further evaluation of alternative stimulation protocols.

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Fig. 1: Trial profile.
Fig. 2: Individual cortical stimulation targets and clinical effects of cTBS stimulation.
Fig. 3: Neuroimaging results.

Data availability

De-identified participant data for research purposes are available on request. Data can only be shared on request due to restrictions laid out in the study’s participant consent forms and QIMR Berghofer data-protection policies. Data will be made available after a data-sharing agreement with QIMR Berghofer has been signed.

Code availability

Code is publicly available at https://github.com/clinical-brain-networks/OCD_Brisbane_TMS_Trial.

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Acknowledgements

This work was supported by the Australian National Health and Medical Research Council (GN2001283, L.C. and S.N.; APP1194070, L.J.H.; APP117302, K.L.G.; APP2008612, M.B.) and philanthropic donations from the Perrin and Dowling family foundations (L.C.). A.Z. was supported by the Rebecca L. Cooper Foundation. We thank S. Thwaites and L. Spoerri for help proofreading the paper.

Author information

Authors and Affiliations

  1. QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia

    Luca Cocchi, Sebastien Naze, Conor Robinson, Lachlan Webb, Saurabh Sonkusare, Luke J. Hearne, Genevieve Whybird, Grace Saffron, Grace Scott, Caitlin V. Hall, Zoie Nott, Jessica Adsett, Katrina L. Grasby, Joshua Jentjens, James G. Scott, Leo Marcus, Emma Savage, Bjorn Burgher & Michael Breakspear

  2. University of Queensland, School of Biomedical Sciences, Faculty of Medicine, Brisbane, Queensland, Australia

    Luca Cocchi & Conor Robinson

  3. Child Health Research Centre, The University of Queensland, South Brisbane, Queensland, Australia

    James G. Scott

  4. Melbourne Neuropsychiatry Centre and Department of Biomedical Engineering, The University of Melbourne, Melbourne, Victoria, Australia

    Andrew Zalesky

  5. School of Psychological Sciences, College of Engineering Science and Environment, University of Newcastle, Callaghan, New South Wales, Australia

    Michael Breakspear

  6. School of Medicine and Public Health, College of Health and Medicine, University of Newcastle, Callaghan, New South Wales, Australia

    Michael Breakspear

  7. Program of Neuromodulation, Hunter Medical Research Institute, New Lambton, New South Wales, Australia

    Michael Breakspear

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  1. Luca Cocchi
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Contributions

L.C. had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. L.C. conceived and designed the study. L.C., S.N., C.R., L.W., S.S., L.J.H., G.W., G.Sa., G.Sc., C.V.H., Z.N., J.A., K.L.G., J.J., J.G.S., L.M., E.S., A.Z., B.B., and M.B. acquired, analyzed, and interpreted the data. L.C. drafted the paper. L.C., S.N., C.R., L.W., S.S., L.J.H., G.W., G.Sa., G.Sc., C.V.H., Z.N., J.A., K.L.G., J.J., J.G.S., L.M., E.S., A.Z., B.B., and M.B. critically revised the paper for important intellectual content. Statistical analyses were completed by L.C., S.N., L.W. and M.B.; L.C., and M.B. obtained the funding. L.C., Z.N., L.M., E.S., and M.B. provided administrative, technical or material support. L.C. and M.B. supervised the work.

Corresponding author

Correspondence to Luca Cocchi.

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Competing interests

The funding bodies supporting this study had no influence on the conduct of the trial, analysis of the data, or reporting of the results. L.C., B.B., L.J.H., C.R., and A.Z. are involved in a not-for-profit clinical neuromodulation center (Queensland Neurostimulation Centre). This center had no role in the present trial. The other authors declare no competing interests.

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Nature Mental Health thanks Gregory Fonzo, Nolan Williams and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Supplementary Tables 1–7, Figs. 1–5, and Clinical trial protocol.

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Cocchi, L., Naze, S., Robinson, C. et al. Effects of transcranial magnetic stimulation of the rostromedial prefrontal cortex in obsessive–compulsive disorder: a randomized clinical trial. Nat. Mental Health 1, 555–563 (2023). https://doi.org/10.1038/s44220-023-00094-0

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