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

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.

Automated summary

This double-blind, sham-controlled study aimed to investigate the antidepressant efficacy of 2 daily prolonged intermittent theta-burst stimulation (piTBS) sessions for treating major depressive disorder (MDD) patients. The results showed that the piTBS group had significantly more responders at week 2 than the sham group, but there was no evidence to support that longer piTBS treatment duration resulted in more rapid or better antidepressant effects. Longer treatment duration did not result in stronger placebo effects.