Effects of accelerated intermittent θ burst stimulation on depressive episodes and cognitive function in adolescents with bipolar disorder

Pharmacological treatments for adolescent bipolar depression often show limited efficacy, safety, and significant side effects concerns. Accelerated intermittent theta burst stimulation (aiTBS) has shown potential in treating depressive episodes, but its application in adolescents with bipolar depression remains unclear. Eighty-six adolescents diagnosed with bipolar depression were randomized to receive 10 sessions of active aiTBS, sham aiTBS, or high-frequency repetitive transcranial magnetic stimulation (HF-rTMS; 10 Hz) targeting the left dorsolateral prefrontal cortex (DLPFC). Treatments were administered once daily over a two-week period. Depressive symptoms were assessed using the 24-item Hamilton Depression Rating Scale (HAMD-24) at baseline and following the completion of treatment. Performance on specific cognitive tasks (assessing working memory, processing speed, and executive function) was evaluated pre- and post-intervention using the Digit Span Test (DST), Digit Symbol Substitution Test (DSST), Trail Making Test Part A (TMT-A), and Trail Making Test Part B (TMT-B). Participants in the aiTBS group demonstrated a greater reduction in HAMD-24 scores compared to the sham group. However, the reduction was not statistically different from the HF-rTMS group. Within the aiTBS group, higher baseline HAMD-24 scores positively predicted a greater reduction of symptoms at both one and two weeks post-treatment. A two-week course of daily aiTBS targeting the left DLPFC appears to be an effective intervention for reducing depressive symptoms in adolescents with bipolar depression, with greater benefits in those with more severe baseline symptoms and efficacy comparable to HF-rTMS. This study was registered in the Medical Research Registration and Filing Information System (Identifier: MR-44-23-000415).