Effectiveness of sequential bilateral repetitive transcranial stimulation versus bilateral theta burst stimulation for patients with treatment-resistant depression (BEAT-D): a randomized non-inferiority clinical trial

Masataka Wada; Shinichiro Nakajima; Keita Taniguchi; Shiori Honda; Yu Mimura; Ryo Takemura; Kevin E Thorpe; Sakiko Tsugawa; Ryosuke Tarumi; Sotaro Moriyama; Naohiro Arai; Ryosuke Kitahata; Hiroyuki Uchida; Shinsuke Koike; Zafiris J Daskalakis; Masaru Mimura; Daniel M Blumberger; Yoshihiro Noda

doi:10.1016/j.brs.2024.12.1474

Effectiveness of sequential bilateral repetitive transcranial stimulation versus bilateral theta burst stimulation for patients with treatment-resistant depression (BEAT-D): a randomized non-inferiority clinical trial

Brain Stimul. 2024 Dec 24:S1935-861X(24)01673-5. doi: 10.1016/j.brs.2024.12.1474. Online ahead of print.

Authors

Masataka Wada¹, Shinichiro Nakajima², Keita Taniguchi², Shiori Honda³, Yu Mimura², Ryo Takemura⁴, Kevin E Thorpe⁵, Sakiko Tsugawa², Ryosuke Tarumi², Sotaro Moriyama², Naohiro Arai⁶, Ryosuke Kitahata⁷, Hiroyuki Uchida², Shinsuke Koike⁸, Zafiris J Daskalakis⁹, Masaru Mimura¹⁰, Daniel M Blumberger¹¹, Yoshihiro Noda¹²

Affiliations

¹ Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, 94305, USA; Department of Neuropsychiatry, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan.
² Department of Neuropsychiatry, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan.
³ Department of Neuropsychiatry, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan; Graduate School of Media and Governance, Keio University, 5322 Endo, Fujisawa-shi, Kanagawa 252-0882 Japan.
⁴ Division of Biostatistics, Clinical and Translational Research Center, Keio University Hospital, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan.
⁵ Dalla Lana School of Public Health, University of Toronto, 155 College St, Toronto, ON M5T 3M7, Canada; Applied Health Research Centre, Li Ka Shing Knowledge Institute of St. Michael's Hospital, 30 Bond St., Toronto, ON, M6R 1B5, Canada.
⁶ Department of Neuropsychiatry, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan; Department of Neuropsychiatry, Faculty of Life Sciences, Kumamoto University, 2-39-1 Kurokami Chuo-ku, Kumamoto 860-8555, Japan.
⁷ Shinjuku-Yoyogi Mental Lab Clinic, 5-27-5 Sendagaya, Shibuyaku, Tokyo, 151-0051, Japan.
⁸ University of Tokyo Institute for Diversity and Adaptation of Human Mind, The University of Tokyo, 3-8-1, Komaba, Meguroku, Tokyo, 153-8902, Japan; Center for Evolutionary Cognitive Sciences, Graduate School of Art and Sciences, The University of Tokyo, 3-8-1, Komaba, Meguroku, Tokyo, 153-8902, Japan; The International Research Center for Neurointelligence, University of Tokyo Institutes for Advanced Study (UTIAS), 3-8-1, Komaba, Meguroku, Tokyo, 153-8902, Japan.
⁹ Department of Psychiatry, University of California, San Diego Health, 8950 Villa La Jolla Dr., La Jolla, California, 92037, United States.
¹⁰ Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, 94305, USA.
¹¹ Temerty Centre for Therapeutic Brain Intervention, Campbell Family Research Institute, Centre for Addiction and Mental Health, 1025 Queen St. W, Toronto, ON M6J 1H4, Canada; Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, 250 College Street, Toronto, ON M5T 1R8, Canada.
¹² Department of Neuropsychiatry, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan; Shinjuku-Yoyogi Mental Lab Clinic, 5-27-5 Sendagaya, Shibuyaku, Tokyo, 151-0051, Japan; Department of Psychiatry, International University of Health and Welfare, Mita Hospital, 1-4-3 Mita, Minato-ku Tokyo, 108-8329 Japan. Electronic address: [email protected].

PMID: 39725000
DOI: 10.1016/j.brs.2024.12.1474

Abstract

Background: Bilateral repetitive transcranial magnetic stimulation (BL-rTMS) over the dorsolateral prefrontal cortex is effective for treatment-resistant depression (TRD). Owing to a shorter treatment time, bilateral theta burst stimulation (BL-TBS) can be more efficient protocol. The non-inferiority of BL-TBS to BL-rTMS was established in late-life TRD; however, this has not been determined in adults of other age groups. Therefore, we investigated the non-inferiority in efficacy of BL-TBS versus BL-rTMS for TRD across a wide range of ages in a randomized, single-blind, multicenter trial.

Methods: The study included 180 participants with major depressive disorder (moderate or greater severity) who were unresponsive to at least one antidepressant treatment between September 2018 and July 2022. Following venlafaxine treatment, patients were randomly assigned to BL-rTMS or BL-TBS (1:1 ratio). The primary outcome was baseline-adjusted Montgomery-Åsberg Depression Rating Scale scores at 6 weeks. The non-inferiority margin of -3.86 was compared against the baseline-adjusted difference. Secondary outcomes included other depression rating scales.

Results: Seventy-seven patients were randomly assigned to BL-rTMS and 81 to BL-TBS, of whom 73 and 76 were assessed for the primary outcome, respectively. There was a -2.44 point difference, favoring BL-rTMS (one-tailed lower 95% CI=-4.19, p=0.091 for non-inferiority), and non-inferiority of BL-TBS was not established. However, non-inferiority was observed for secondary outcomes. The all-cause dropout rates and number of adverse effects were similar between them.

Conclusion: Our study could not establish the non-inferiority of BL-TBS compared to BL-rTMS in terms of efficacy for patients with TRD across the adult lifespan.

Keywords: major depressive disorder; non-inferiority study; randomized controlled study; repetitive transcranial magnetic stimulation; theta burst stimulation; treatment resistant depression.