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NCT07111390). W76. SAFETY AND EFFICACY OF FULL AND HALF-DOSE NEURONAVIGATED ACCELERATED THETA BURST TMS IN TREATMENT-NAïVE ADOLESCENT DEPRESSION

Sean O'Sullivan — Elyse Lemke1, Emma Ableman1, Juneid Mosaheb1, Austin Herrman1, J. Michele LaGrone1, Charles Nemeroff1, Nolan Williams2 1The University of Texas at Austin, 2Stanford University School of Medicine

2026 ASCP Annual Meeting

Rates of adolescent depression have risen to crisis levels in recent years, yet first-line treatment options remain limited by modest efficacy, delayed onset, and a considerable sideeffect burden. There is a pressing need for novel, safe, and rapid acting interventions. Accelerated fMRI-guided intermittent theta burst stimulation (aiTBS) delivering 10 daily TMS sessions over 5 consecutive days has demonstrated high efficacy, rapid onset, and minimal side effects in adults with treatment-resistant depression leading to FDA clearance in this population. We investigate this aiTBS protocol as a first-line intervention in adolescents with major depression without concurrent or prior pharmacotherapy or psychotherapy. To investigate convenience, tolerability, and dose finding in this novel population, one arm of this pilot trial received a half-dose aiTBS protocol that maintains standard stimulation parameters but reduces the number of daily sessions from 10 to 5.

Methods

All participants receive an fMRI at baseline for individualized precision targeting of the left dorsolateral prefrontal cortex. Primary outcomes include safety, tolerability, and efficacy assessed through systematic side-effect checklists, adverse-event monitoring, and change in the Children’s Depression Rating Scale-Revised (CDRS-R) from baseline to one month following treatment. Secondary outcomes include preference, convenience, and overall acceptability of aiTBS as a first-line treatment in this population. Semi-structured interviews with participants and parents as well the Treatment Acceptability Questionnaire are conducted at baseline, immediately post-treatment, and at 1-, 3-, and 6-month follow-up visits. Post-treatment fMRIs measure exploratory changes in functional connectivity with treatment.

Results

To date, 18 participants have been enrolled. 8 have failed screening either due to psychiatric comorbidity or dental hardware which disrupted fMRI targeting. Two participants dropped out prior to treatment, both due to time commitment. 7 participants have completed treatment: 3 full-dose and 4 half-dose. One half-dose participant was unable to tolerate the stimulation intensity consistent with the protocol. Of the 6 participants who received the full or half-dose protocol, 5 met depression remission criteria (≤28 CDRS-R raw score) with one only meeting response criteria missing remission by 1 point on the CDRS-R scale. 4 of these participants completed their 3-month follow up visits at which time they maintained depression remission criteria.

Conclusions

Preliminary findings suggest that this trial is feasible and that aiTBS is safe and effective as a first-line treatment for adolescent depression. Preliminary efficacy results suggest no difference between the full-dose and half-dose protocol opening the door to a more convenient and lower cost option for this population. One participant who did not achieve remission at the one-month follow-up received the half-dose protocol, but was unable to tolerate an appropriate treatment intensity.