Abstract: Background: Repetitive transcranial magnetic stimulation (rTMS) combined with antidepressants has emerged as a novel therapy for treating depression in children and adolescents. However, predicting early treatment efficacy remains a significant challenge. Objective: To explore potential factors that could predict long-term efficacy during rTMS combined with antidepressant therapy. Design: Retrospective cohort study. Methods: The cohort included children and adolescents under 18 years of age who were newly diagnosed with moderate to severe unipolar or bipolar depression, received rTMS treatment continuously for at least 20 sessions during hospitalization, had daily symptom index (DI-5) scores recorded, and had Hamilton Depression Rating Scale (HAMD) scores recorded before and after the 20th rTMS session. Participants were divided into response and non-response groups based on whether their final HAMD score showed a reduction of ≥50% from baseline. Correlation analysis was conducted between DI-5 and HAMD scores. If a strong correlation was found, the potential of DI-5 assessments during rTMS treatment to predict early response was evaluated. Main outcome measures: Correlation between DI-5 and HAMD scores. Results: A total of 228 children and adolescents with moderate to severe unipolar or bipolar depression met the inclusion and exclusion criteria. The mean age was 14.0 ± 3.0 years, and 111 (48.6%) were male. The Pearson correlation coefficients between DI-5 and HAMD scores before and after rTMS treatment were 0.70 and 0.72, respectively, with both being statistically significant (P< 0.001). After 20 rTMS sessions, there were 101 participants in the response group and 127 in the non-response group. There were no statistically significant differences between the two groups in gender distribution, age, single-parent household proportion, left-behind children proportion, family psychiatric history, age of symptom onset, symptom duration, learning disabilities, language disorders, motor development disorders, weight, height, medication duration, counseling sessions, thyroid dysfunction, time to fall asleep, frequency of dreaming, and picky eating habits (P>0.05). Baseline DI-5 and HAMD scores also showed no statistically significant differences between the response and non-response groups (P>0.05). However, DI-5 scores after the 20th rTMS session were significantly different between the response and non-response groups (P<0.001), as were the final HAMD scores (P<0.001). On the 11th session, the DI-5 scores showed a statistically significant difference between the response and non-response groups (P<0.001). A median reduction of 2 points in DI-5 scores was used as a stratification basis. In the group with a reduction of <2 points on the DI-5 scale, 107 participants (46.9%) had a 98.1% probability of being in the non-response group by the 20th rTMS session. In the group with a reduction of ≥2 points, 64 participants (87.4%) had an 89.2% probability of being in the response group by the 20th rTMS session. Conclusion: A reduction of ≥2 points on the DI-5 scale by the 11th rTMS session may serve as an early predictor of treatment efficacy for rTMS combined with antidepressants in children and adolescents with depression.

Key words: Repetitive transcranial magnetic stimulation, Children and adolescents, Depression, Outcome prediction, Daily symptom index