Efficacy of iTBS in adolescent depression: effects on anhedonia and exploratory moderation analyses

To examine the efficacy of intermittent theta burst stimulation (iTBS) for depressive symptoms and anhedonia in adolescents with depression, and explore potential moderators of treatment response.

We conducted a randomized controlled trial enrolling 60 adolescents (11-19 years) with depression from a tertiary hospital in Anhui Province, China; with participant-and assessor-blinding, whereas TMS operators were not. Participants were allocated by an independent researcher using a computer-generated random number list to active iTBS (n = 30) or sham stimulation (n = 30). The intervention was delivered over two weeks (10 treatment days), with three sessions per weekday(30 sessions total). Clinical assessments were performed at baseline and post-intervention using standardized instruments: the Hamilton Depression Rating Scale-17 items (HAMD-17), Hamilton Anxiety Rating Scale-14 items (HAMA-14), and Temporal Experience of Pleasure Scale (TEPS). Treatment effects were examined using 2 × 2 repeated-measures ANOVA, and exploratory moderation was examined using PROCESS Model 1 with 5000 bootstrap resamples, with Holm-Bonferroni correction applied across five interaction tests.

Baseline clinical scale scores were comparable between groups (P > 0.05). Following treatment, significant group× time interactions indicated greater improvement in the active iTBS group than sham on depressive symptoms (HAMD-17: F = 40.300, P < 0.001) and anxiety symptoms (HAMA-14: F = 23.802, P < 0.001). Significant group× time interactions were also observed for TEPS total and its four subscales (P < 0.05). In exploratory moderation analyses, the Group×baseline TEPS-AA interaction was nominally significant(P = 0.014) but did not survive Holm-Bonferroni correction(adjusted P = 0.070).

iTBS was feasible and associated with greater short-term improvements in depressive symptoms and anhedonia in adolescents compared with sham stimulation. Exploratory analyses indicated that baseline hedonic traits (particularly abstract anticipatory pleasure) may be related to differential treatment response, but moderation effects should be interpreted cautiously given multiple-testing correction and require confirmation in adequately powered trials with longer follow-up. These findings support further investigation of iTBS for adolescent depression and the prospective evaluation of candidate predictors of response. Generalizability may be limited by the single-center design and the accelerated treatment schedule.