Repetitive transcranial magnetic stimulation (rTMS) as an early intervention in Major Depressive Disorder (MDD) compared to antidepressant selective serotonin reuptake inhibitor (SSRI) medication (Early-TMS)

• Applicant: Professor Dr. Christian Plewnia
• Subject Area: Clinical Psychiatry, Psychotherapy, Child and Adolescent Psychiatry ; Biological Psychiatry
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 549350865

The aim of this project is to conduct a controlled phase II clinical trial to test the feasibility and to determine effect sizes of theta burst stimulation (TBS) as an early intervention for patients suffering from Major Depressive Disorder (MDD) in comparison to standard antidepressant treatment with a Serotonin-Reuptake-Inhibitor (SSRI). Despite their proven effectiveness, non-pharmacological treatment methods such as repetitive transcranial magnetic stimulation (rTMS) are currently only recommended in the guidelines if several therapy attempts have already failed. The demand for psychotherapeutic treatment opportunities exceeds the available capacities, so that in most cases psychopharmacological treatment is initiated. However, only about 50% of patients benefit from this first treatment attempt. In order to avoid treatment resistance and chronification and to improve patients' quality of life, it would be helpful to offer non-pharmacological treatment options such as rTMS at an early stage of disease. This could also have a positive impact on patient autonomy, as expanding the range of treatment options would significantly strengthen the process of participatory decision-making with regard to the development of an individualized treatment plan. We plan to conduct a therapy response-adapted, two-staged, randomized and controlled phase II clinical trial. Initially, the study participants will be randomized to two treatment arms (Stage I: 4 weeks TBS vs. SSRI). After completion of Stage I, the allocation to Stage II (4 weeks) occurs therapy response-adapted. The type of further treatment depends on whether a remission, a treatment response or non-response has occurred in Stage I. If remission has been achieved, the treatment form already applied is continued as maintenance therapy. In the case of non-response, a switch to the other treatment arm takes place. For patients who show a treatment response but have not achieved remission, the corresponding patient preference is given special consideration for Stage II and thus determines the type of further treatment. Depending on patient preference, it is therefore possible both to continue treatment from Stage I and to switch to the other treatment arm. The study aims to answer the question of whether a 4-week bilateral TBS is not inferior to standard antidepressant treatment with an SSRI in drug-naïve patients with MDD in terms of efficacy and tolerability. The results will provide the basis for implementation of a confirmatory, multicentre phase III study to expand the range of treatment options for patients with MDD.

• DFG Programme: Clinical Trials
• Co-Investigators: Dr. Julia Becker-Sadzio; Professor Dr. Andreas Jochen Fallgatter