The longer, the better ? Longer left-sided prolonged intermittent theta burst stimulation in patients with major depressive disorder: A randomized sham-controlled study

Cheng-Ta Li; Chih-Ming Cheng; Hui-Ching Lin; Skye Hsin-Hsieh Yeh; Jia-Shyun Jeng; Hui-Ting Wu; Ya-Mei Bai; Shih-Jen Tsai; Tung-Ping Su; Paul B Fitzgerald

doi:10.1016/j.ajp.2023.103686

The longer, the better ? Longer left-sided prolonged intermittent theta burst stimulation in patients with major depressive disorder: A randomized sham-controlled study

Asian J Psychiatr. 2023 Sep:87:103686. doi: 10.1016/j.ajp.2023.103686. Epub 2023 Jun 26.

Authors

Affiliations

¹ Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan; Division of Psychiatry, School of Medicine, National Yang-Ming Chiao-Tung University, Taipei, Taiwan; Institute of Brain Science and Brain Research Center, School of Medicine, National Yang-Ming Chiao-Tung University, Taipei, Taiwan; Institute of Cognitive Neuroscience, National Central University, Jhongli, Taiwan; School of Medicine, National Defense Medical Center, Taipei, Taiwan. Electronic address: ctil2@vghtpe.gov.tw.
² Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan; Division of Psychiatry, School of Medicine, National Yang-Ming Chiao-Tung University, Taipei, Taiwan; Institute of Brain Science and Brain Research Center, School of Medicine, National Yang-Ming Chiao-Tung University, Taipei, Taiwan; School of Medicine, National Defense Medical Center, Taipei, Taiwan.
³ Department and Institute of Physiology, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; School of Medicine, National Defense Medical Center, Taipei, Taiwan.
⁴ Institute of Brain Science and Brain Research Center, School of Medicine, National Yang-Ming Chiao-Tung University, Taipei, Taiwan; School of Medicine, National Defense Medical Center, Taipei, Taiwan.
⁵ Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan; Division of Psychiatry, School of Medicine, National Yang-Ming Chiao-Tung University, Taipei, Taiwan; School of Medicine, National Defense Medical Center, Taipei, Taiwan.
⁶ School of Medicine, National Defense Medical Center, Taipei, Taiwan; School of Medicine and Psychology, Australian National University, Canberra, ACT, Australia.

PMID: 37406605
DOI: 10.1016/j.ajp.2023.103686

Abstract

Background: Prolonged intermittent theta-burst stimulation (iTBS) is effective for major depressive disorder (MDD). However, whether longer piTBS treatment in a single session could have antidepressant efficacy remains elusive. Therefore, this double-blind, randomized, sham-controlled study aimed to investigate the antidepressant efficacy of 2 daily piTBS sessions for treating MDD patients with a history of poor responses to at least 1 adequate antidepressant trial in the current episode.

Methods: All patients received 2 uninterrupted sessions per day for 10 weekdays (i.e., 2 weeks; a total of 20 sessions). Seventy-two patients were recruited and 1:1:1 randomly assigned to one of three groups: piTBS (piTBSx2), 10-Hz rTMS (rTMSx2), or sham treatment (shamx2, randomly assigned to piTBS or rTMS). 10-Hz rTMS group was included as an active comparison group to enhance assay sensitivity.

Results: piTBSx2 group had significantly more responders at week 2 than shamx2 group, but it did not yield better antidepressant effects regarding the %depression changes. The changes of antidepressant scores were not different among the three groups at week 1 (-26.2% vs. -23.3% vs. -22.%) or at week 2 (-34.1% vs. -37.1% vs. -30.1%). Longer treatment duration did not result in stronger placebo effects [sham(piTBS)x2: - 31.7% vs. sham(rTMS)x2: - 26.7%].

Conclusion: The present sham-controlled study confirmed that piTBS is an effective antidepressant option, but found no evidence to support that longer piTBS treatment duration resulted in more rapid or better antidepressant effects. A high placebo effect was observed, but longer treatment duration of brain stimulation was not linearly associated with stronger placebo effects.

Keywords: Placebo; Prolonged; Repetitive transcranial magnetic stimulation; Theta burst stimulation; Treatment-resistant depression.