Efficacy and Safety of Accelerated Intermittent Theta Burst Stimulation for Adolescents With Major Depressive Disorder: A Randomized, Double-Blind, Sham-Controlled Study

Abstract

Background: Developing safe and rapid treatments is crucial for adolescent major depressive disorder (MDD). While 10-session daily accelerated intermittent theta burst stimulation (a-iTBS) is effective in adults, its duration and safety limit its use in adolescents. In this study, we evaluated a 5-session daily a-iTBS protocol for adolescents with non-treatment-resistant MDD.

Methods: Seventy-four adolescents with non-treatment-resistant MDD were randomly assigned to a-iTBS or a sham group. The a-iTBS group underwent 5 sessions of 1800-pulse iTBS per day targeting the left dorsolateral prefrontal cortex (Montreal Neurological Institute [MNI] coordinates: -44, 40, 29) using neuronavigation for 10 consecutive days, while the sham group received intervention with a sham coil that provided haptic sensations and audible sounds. The 17-item Hamilton Depression Rating Scale (HAMD-17), Hamilton Anxiety Rating Scale, and Children's Depression Inventory were rated at baseline, the first day after the innervation (day 11), and the 1-month and 3-month follow-ups.

Results: The a-iTBS group showed a significantly greater reduction in HAMD-17 scores than the sham group at day 11 (p < .001, Cohen's d = 0.86 [95% CI, 0.38 to 1.33]) and the 1-month follow-up (Cohen's d = 0.72 [95% CI, 0.24 to 1.18]). However, there was no statistically significant difference between the 2 groups at the 3-month follow-up (p = .17, Cohen's d = 0.33 [95% CI, -0.13 to 0.79]). The a-iTBS group showed significantly greater improvements in anxiety and self-reported depression than the sham group at all time points (all p values < .05).

Conclusions: a-iTBS was a safe and effective treatment for adolescents with non-treatment-resistant MDD, but the therapeutic effect diminished at the 3-month follow-up. Although the study was blinded, clinician identification exceeded random chance in the a-iTBS group, which suggests that blinding might have been partially compromised.

Keywords: Accelerated intermittent theta burst stimulation; Adolescent major depressive disorder; Left dorsolateral prefrontal cortex; Randomized controlled trial; Transcranial magnetic stimulation.