Non-inferiority of intermittent theta burst stimulation over the left V1 vs. classical target for depression: A randomized, double-blind trial

Yan Kong; Jiawei Zhou; Mingge Zhao; Yuhua Zhang; Tingting Tan; Zhi Xu; Zhenghua Hou; Yonggui Yuan; Liangliang Tan; Ruize Song; Yachen Shi; Haixia Feng; Wei Wu; Yang Zhao; Zhijun Zhang

doi:10.1016/j.jad.2023.09.024

Non-inferiority of intermittent theta burst stimulation over the left V₁ vs. classical target for depression: A randomized, double-blind trial

J Affect Disord. 2023 Dec 15:343:59-70. doi: 10.1016/j.jad.2023.09.024. Epub 2023 Sep 24.

Authors

Yan Kong¹, Jiawei Zhou², Mingge Zhao³, Yuhua Zhang⁴, Tingting Tan⁴, Zhi Xu⁴, Zhenghua Hou⁴, Yonggui Yuan⁴, Liangliang Tan⁴, Ruize Song⁵, Yachen Shi⁵, Haixia Feng³, Wei Wu⁶, Yang Zhao⁷, Zhijun Zhang⁸

Affiliations

¹ Department of Neurology, Affiliated Zhongda Hospital, School of Medicine, Institution of Neuropsychiatry, Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing 210009, China; Department of Clinical Psychology, The Second Affiliated Hospital of Shandong First Medical University, Taian 271000, China.
² Department of Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
³ Department of Nursing, Affiliated Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China.
⁴ Department of Psychosomatics and Psychiatry, Affiliated of Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China.
⁵ Department of Neurology, Affiliated Zhongda Hospital, School of Medicine, Institution of Neuropsychiatry, Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing 210009, China.
⁶ Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford 94305, USA.
⁷ Department of Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 211166, China. Electronic address: yzhao@njmu.edu.cn.
⁸ Department of Neurology, Affiliated Zhongda Hospital, School of Medicine, Institution of Neuropsychiatry, Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing 210009, China; Department of Mental Health and Public Health, Faculty of Life and Health Sciences, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China; Research Center for Brain Health, Pazhou Lab, Guangzhou 510330, China. Electronic address: janemengzhang@vip.163.com.

PMID: 37751801
DOI: 10.1016/j.jad.2023.09.024

Abstract

Background: Repetitive transcranial magnetic stimulation (rTMS) targeting the visual cortex (VC) has shown antidepressant effects for major depressive disorder (MDD) in sham-controlled trials, but comparisons with rTMS targeting the left dorsolateral prefrontal cortex (DLPFC) are lacking. We aimed to determine the non-inferiority of intermittent theta-burst stimulation (iTBS) over VC vs DLPFC for MDD.

Methods: Participants randomly received navigated iTBS over the left V₁ or the left DLPFC twice daily for 14 days with a 3-month follow-up. The primary outcome was change in Hamilton Depression Rating Scale (HAMD-17) score from baseline to treatment end, with 2.5 points as the non-inferiority margin. Secondary outcomes included: improvement in Montgomery-Asberg Depression Rating Scale (MADRS), Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA); response and remission rates; suicidal ideation and adverse events.

Results: Of 75 randomized patients, 67 completed full treatment, including 52 first-episode patients and 15 relapsers. The primary outcome indicated the non-inferiority of VC (adjusted difference 1.14, lower 97.5 % CI -1.24; p = .002), confirmed by improvements in objective cognitive task and protein levels, as did most secondary outcomes. Reduced suicidal ideation after treatment, incidence of eye discomfort and pain score were lower in the VC group.

Conclusions: Left VC iTBS has the potential to be non-inferior to DLPFC iTBS in most first-episode MDD in improving depressive symptoms and cognitive function, with less suicidal ideation and adverse events.

Limitations: Given the limited sample size, the lack of a sham control and the use of antidepressants, the findings should be interpreted with caution.

Keywords: Biomarker; Emotional Stroop task; Intermittent theta burst stimulation; Major depressive disorder; Non-inferiority trial; Protein; Visual cortex.