# High dosage accelerated intermittent theta burst stimulation without precision targeting and dosing in depression: an open-label pilot study

## TL;DR

This pilot study tested a high-dose brain stimulation treatment for depression without personalized targeting and found it had some antidepressant effects, though less effective than previously reported methods.

## Contribution

The study evaluates the effectiveness of high-dose aiTBS without precision targeting in depression treatment.

## Key findings

- Mean MADRS scores decreased significantly after one month of aiTBS treatment.
- Response and remission rates were 50% and 12.5% at one month, but declined over time.
- Effectiveness of aiTBS without precision targeting was lower than previously reported precision-based approaches.

## Abstract

High dosage accelerated intermittent theta-burst stimulation (aiTBS) protocols (10 sessions per day for 5 days) combined with precision targeting and depth adjusted iTBS intensity yield high response and remission rates in depression. However, disentangling their efficacy components to develop pragmatic mental health solutions is challenging. This pilot study applied such a high dosage aiTBS protocol without using any precision features.

Eight patients with treatment-resistant depression (TRD) underwent open-label aiTBS targeting the left dorsolateral prefrontal cortex (DLPFC) using the Beam F3 algorithm. Over 5 days, patients received 50 aiTBS sessions, each delivering 1800 pulses at 90% resting motor threshold with 50-min inter-session intervals. All patients underwent a 4 weeks follow-up without stimulation, were offered tDCS for 4 weeks thereafter and had a final follow-up after 6 months. Treatment effects were assessed by clinical and cognitive measures.

Patients received 46 aiTBS sessions on average. At one-month follow-up, mean MADRS scores decreased by -12.50 ± 9.81 (Cohen’s d = 2.83; 95% CI, 2.34–3.32; p < 0.001), with response and remission rates of 50% and 12.5%, respectively. After tDCS, 28.6% and 14.3% sustained response and remission, which declined to 16.7% and 0% at six months.

This pilot trial evidenced the antidepressant effect of a high dosage aiTBS protocol comparable with the Stanford Neuromodulation Therapy (SNT) approach but without individualized precision components. Its effectiveness appeared lower than previously reported for SNT. Randomized controlled trials should systematically investigate the contribution of precision components to the overall effectiveness of aiTBS in depression.

This trial is a part of a real-world clinical study of non-invasive brain stimulation treatments conducted at our department (preregistered at DRKS-ID: DRKS00024776, drks.de).

The online version contains supplementary material available at 10.1007/s00406-025-02067-z.