Efficacy and safety of intermittent theta burst stimulation on adolescents and young adults with major depressive disorder: A randomized, double blinded, controlled trial

Background: Intermittent theta burst stimulation (iTBS) is a newer form of Repetitive Transcranial Magnetic Stimulation (rTMS) for depression. However, its efficacy and safety in adolescents and young adults with major depressive disorder (AYA-MDD) have not been well studied, especially when applied with a strategy that combines neuronavigation targeting and accelerated iTBS. Methods: In this study, ninety patients were randomly assigned to twice-daily (two 600-pulse sessions spaced out by 10 min, n = 31), once-daily (one 600-pulse session, n = 29) or sham iTBS (no pulses, n = 30) groups for 10 treatment days. The primary outcome measure was the change in depression scores on the Hamilton Rating Scale for Depression (HAMD-17). Other clinical symptoms, such as anxiety, were also evaluated. Results: Linear mixed model analysis found that scores on the HAMD-17 and its factors improved in all three groups, but these improvements did not significantly differ among groups. Other clinical symptoms such as anxiety also improved. Response and remission rates were relatively low and did not differ among groups at any time point. The most common adverse event was headache, and the proportion of participants who reported headache in the twice-daily and once-daily groups was significantly higher than that in the sham group. Conclusions: The current results indicated that twice-daily and once-daily iTBS under neuronavigation are safe and well tolerated in AYA-MDD, but the overall efficacy was not superior to that of sham treatment. We speculated several possible reasons such as the high placebo response of the young population, inadequate iTBS pulses and so on.