Efficacy and Safety of Accelerated Intermittent Theta-Burst Stimulation for Adolescents with Major Depressive Disorder:A Randomized Clinical Trial

Abstract

Importance: The incidence of major depressive disorder (MDD) is increasing during adolescence. Pharmacotherapy and psychotherapy are commonly used treatments, but they often come with significant delays in effect or side effects. The safety and efficacy of accelerated intermittent Theta Burst Stimulation (a-iTBS) for treating adolescent MDD remain unclear and warrant further investigation.

Objective: To explore the safety and efficacy of a-iTBS in treating adolescents with MDD.DESIGN, SETTING, AND PARTICIPANTS
This study is a single-center, double-blind, sham-controlled, randomized clinical trial conducted from April 12, 2024, to November 2, 2024. A total of 74 adolescent patients with MDD were enrolled. Participants were recruited through advertisements and referrals. Participants were aged 12 to 18 years, primarily diagnosed with MDD, a 17-item Hamilton Depression Rating Scale (HAMD-17) score ≥17, and previously had not received transcranial magnetic stimulation (TMS) treatment.

Interventions: Participants were randomly assigned in a 1:1 ratio to two groups: the a-iTBS group and the sham group. The a-iTBS group received iTBS five times daily, with each session lasting 10 minutes and delivering 1800 pulses at 90% of the resting motor threshold, targeting the left dorsolateral prefrontal cortex (DLPFC), for a total of 10 consecutive days. The sham group received sham stimulation using a pseudostimulation coil that emitted only sound without delivering any actual magnetic pulses.

Main Outcomes and Measures: The primary outcome was the changes of depressive symptom as measured by HAMD-17 at baseline, cand during the month 1 and 3 follow-up periods. Secondary outcomes included rates of clinical response and remission, the changes of anxiety symptom as measured by the Hamilton Anxiety Scale and depressive symptoms as self-reported measured using the Children's Depression Inventory (CDI), all at the same time points.

Results: A total of 74 participants (59 females [79.73%]: mean age [SD],14.35 [1.50]) were included. As a primary outcome, patients who received a-iTBS showed a significantly greater reduction in mean (SD) HAMD-17 total score compared with patients in sham group after the a-iTBS treatment (a-iTBS: 8.09 [4.14], the sham group: 12.28 [5.57], P < .001, Cohen’d = 0.86 [95% CI, 0.38 - 1.33]) and month 1 follow-up (a-iTBS: 0.33 [3.26], the sham group: 1248 [2.69], P = .003, Cohen’d = 0.72 [95% CI, 0.24-1.18]) with a significant group by time interaction (F3, 219 = 7.66, P < .001, Cohen's d = 0.64).

Conclusions and Relevance: This trial found that a-iTBS was a safe and effective treatment for adolescents with MDD.

Trial Registration: The trial was registered at the website of https://www.chictr.org.cn/showproj.html?proj=218231 (Trial Number: ChiCTR2400083002)

Funding: The study was supported by the Ningbo medical and health brand discipline (No.PPXK 2024-07), and the Ningbo Top Medical and Health Research Program (No.2022030410), Humanities and Social Sciences Project of the Ministry of Education (No. 24YJCZH129) and Zhejiang Province Medical and Health Science and Technology Plan Project (No.2024KY349).

Declaration of Interest: No potential confilct of interest was reported by the authors.

Ethical Approval: The study received approval from the Ethics Committee of Ningbo Kangning Hospital.

Keywords: accelerated Intermittent Theta-burst Stimulation, Adolescents with Major Depressive Disorder, Randomized Clinical Trial