Antidepressant response time across intermittent theta burst stimulation regimens and efficacy indicators in adolescents depression: a secondary analysis from a randomized controlled trial

Background: Accelerated intermittent theta burst stimulation (aiTBS), which involves the administration of multiple daily sessions of iTBS, represents a novel regimen of repetitive transcranial magnetic stimulation. Studies have suggested that aiTBS may facilitate a fast response among patients with major depressive disorders. However, whether aiTBS can accelerate antidepressant response in adolescents suffering from depression is still unclear. Additionally, the potential indicators associated with antidepressant response in this population are still understudied.

Methods: Ninety adolescents with depression were recruited and randomly assigned to aiTBS (two 600-pulse sessions of iTBS spaced for 10 min, N = 31), iTBS (one 600-pulse session, N = 29), or sham iTBS (N = 30) for two treatment weeks. Kaplan-Meier analysis was used to estimate the mean time to antidepressant response among the three groups. The analysis of covariance and the multiple logistic regression were applied to identify potential indicators associated with treatment response.

Results: The mean time to antidepressant response was 7.45 weeks (95% CI: 6.19-8.72) in the aiTBS group, 5.62 weeks (95% CI: 4.09-7.16) in the iTBS group, and 5.07 weeks (95% CI: 3.56-6.58) in the sham group, respectively. The log rank test revealed no significant difference in the mean time to antidepressant response among the three groups (χ² = 4.156, p = 0.125). For the antidepressant response, there were also no significant interactions between iTBS treatment regimens and the baseline characteristics. Notably, participants with higher motor threshold and worse global function at baseline were likely to be associated with early response and final response, respectively, while those who experiencing child-parent separation were associated with both early and final response. In addition, younger participants were more likely to experience recurrence during follow-up.

Conclusions: aiTBS did not demonstrate an advantage in terms of a fast antidepressant response. However, some pretreatment characteristics might serve as indicators of antidepressant response. This relatively simple application based on pretreatment characteristics seems to be a cost-effective method to identify adolescents who are more likely to develop an early antidepressant response and sustain it.

Trial registration: This is a secondary analysis of a primary RCT, which was officially registered in the Chinese Clinical Trial Registry at 19/1/2021 with the number of ChiCTR2100042346. https://www.chictr.org.cn/bin/project/edit?pid=66118 .