Bilateral theta burst stimulation as an add-on to schema therapy in major depression: methods and design of a randomized, sham-controlled study

Abstract Schema therapy (ST) is an integrative psychotherapeutic treatment that may be as effective as cognitive behavioural therapy in treating depression. Novel approaches are focusing on augmenting psychiatric treatments with brain stimulation techniques, like repetitive transcranial magnetic stimulation (rTMS), to enhance efficacy. Therefore, this randomized, sham-controlled, prospective and double-blind study (for two of the three treatment groups) will aim to evaluate the effects of augmenting ST with bilateral theta burst stimulation (TBS), a specialized rTMS protocol, in patients with major depression receiving routine ST inpatient or day-hospital care. We hypothesize that active TBS will show a greater reduction in depressive symptoms than sham and no TBS (control). Approximately 120 patients with major depression who are undergoing 8- to 10-week ST will be randomly assigned to additionally receive 4-weeks of bilateral active TBS, bilateral sham TBS, or no TBS. TBS will be administered as intermittent TBS (iTBS) to the left side of the dorsolateral prefrontal cortex to increase and continuous TBS (cTBS) to the right to decrease excitability. Depressive symptoms will be assessed with the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Beck Depression Inventory-II (BDI-II). Functional levels will be assessed with the Global Assessment of Functioning (GAF) scale, and therapy-specific changes with the Young Schema Questionnaire (YSQ-S3R). Differences in efficacy between groups will be analyzed by linear mixed model repeated measures. This forthcoming study is expected to provide important insights into potential benefits of combining ST with bilateral TBS in patients with major depression and may lead to more effective therapeutic strategies. Trial registration: DRKS00039152 registered 10/02/2026.