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. This study evaluated a five-session daily a-iTBS protocol for adolescents with non-treatment-resistant MDD.

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

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

Conclusion: A-iTBS is a safe and effective treatment for adolescents with non-treatment-resistant MDD, but the therapeutic effect diminished at the month 3 follow-up.

Limitation: Although the study was blinded, clinician identification exceeded random chance in the a-iTBS group, suggesting that blinding may have been partially compromised.