Effectiveness of Clustered Versus Tapered Repetitive Transcranial Magnetic Stimulation (rTMS) as Maintenance Therapy Following Successful Acute rTMS Treatment in Patients With Depressive Syndrome (ERTE)

Effectiveness of rTMS as Maintenance Therapy; Clustered rTMS vs. Tapered rTMS

The goal of this clinical trial is to compare two maintenance transcranial magnetic stimulation (rTMS) strategies following successful acute theta burst stimulation (TBS) treatment in adults with depressive syndrome. It will also evaluate whether the two maintenance strategies differ in their ability to maintain the antidepressant treatment response over 24 weeks. The main questions it aims to answer are:

Does clustered maintenance rTMS reduce the risk of depressive relapse or clinically relevant symptom worsening compared with tapered maintenance rTMS? Do the two maintenance strategies differ in depressive symptoms, global clinical status, psychosocial functioning, and MRI-based biomarkers over time?

Researchers will compare a clustered maintenance rTMS protocol with a tapered maintenance rTMS protocol.

Participants will:

• Complete successful acute TBS treatment before study enrollment
• Be randomly assigned to either clustered or tapered maintenance rTMS
• Receive 20 maintenance stimulation sessions over 20 weeks
• Attend clinical follow-up assessments every 4 weeks for a total follow-up -period of 24 weeks
• Undergo optional multimodal MRI examinations at the Munich study site

Study Overview

• Status: Not yet recruiting
• Conditions: Major Depressive Disorder (MDD); Depressive Episodes; Depressive Syndrome
• Intervention / Treatment: Device: Repetitive Transcranial Magnetic Stimulation (rTMS), Theta Burst Stimulation

Detailed Description

Repetitive transcranial magnetic stimulation (rTMS), including intermittent theta burst stimulation (iTBS), is an established treatment for depressive disorders. While the efficacy of acute treatment has been demonstrated in numerous clinical trials, a substantial proportion of patients experience symptom worsening or relapse following successful acute treatment if no maintenance therapy is provided. Several maintenance strategies have been proposed, including tapered treatment schedules with gradually decreasing treatment frequency and clustered treatment schedules consisting of repeated blocks of consecutive stimulation sessions. However, the available evidence is limited, and no randomized controlled trial has directly compared these two maintenance approaches using identical treatment duration and the same total number of stimulation sessions.

This prospective, randomized, controlled, two-center study aims to compare two maintenance treatment strategies following successful acute iTBS in adults with depressive syndrome. Patients who achieve response or remission after a standardized acute iTBS treatment course will be randomized in a 1:1 ratio to either a tapered maintenance protocol or a clustered maintenance protocol. Randomization will be stratified by study site and baseline depression severity. Because of the different treatment protocols, blinding of participants and treating clinicians is not feasible. MRI data analyses will be performed blinded to treatment allocation.

Both maintenance protocols include 20 stimulation sessions delivered over a 20-week maintenance period following a four-week stimulation-free interval after completion of the acute treatment phase. The treatment protocols differ only in the temporal distribution of maintenance sessions. The tapered protocol gradually reduces treatment frequency over time, whereas the clustered protocol delivers stimulation in four clusters of five consecutive daily sessions.

The primary objective is to compare the time to depressive relapse or clinically relevant symptom worsening during the 24-week follow-up period. Clinically relevant symptom worsening is defined using predefined changes in the Montgomery-Åsberg Depression Rating Scale (MADRS), and relapse is defined as the recurrence of at least moderate depressive symptoms together with loss of the previously achieved treatment response.

Secondary objectives include comparing longitudinal changes in depressive symptom severity, patient-reported depressive symptoms, global clinical status, and psychosocial functioning using the MADRS, Beck Depression Inventory (BDI), Clinical Global Impression (CGI), and Global Assessment of Functioning (GAF), respectively.

An additional objective of the study is to investigate neurobiological correlates of maintenance treatment using multimodal magnetic resonance imaging (MRI). At the Munich study site, participants will be offered optional multimodal MRI examinations. Participation in the MRI component is voluntary and is not required for participation in the clinical trial. MRI assessments include resting-state functional MRI, arterial spin labeling, diffusion imaging including NODDI, and quantitative MRI. These analyses aim to identify imaging biomarkers associated with maintenance of antidepressant effects, symptom worsening, and relapse risk following maintenance iTBS. Participation in the MRI component is optional and is not required for participation in the clinical trial.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ulrike Vogelmann, Senior physician; Phone Number: 089/4140-6882; Email: ulrike.vogelmann@mri.tum.de

Study Locations

• Germany
  • Bavaria
    • Munich, Bavaria, Germany, 81675
      • TUM Universitiy Hospital, Department for Psychiatry and Psychotherapy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥18 years
• Diagnosis of a depressive syndrome
• Completion of an acute treatment course consisting of 20 sessions of theta burst stimulation (TBS) over 4 weeks
• Response or remission following acute treatment. Response is defined as a ≥50% reduction in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score
• Remission is defined as a MADRS total score ≤10.
• Clinical eligibility for maintenance TBS
• Provision of written informed consent

Exclusion Criteria:

• Non-response to acute TBS treatment
• Contraindications to transcranial magnetic stimulation (TMS) or theta burst stimulation (TBS)
• Active substance use disorder (substance use within the past 3 months)
• Acute psychiatric or medical conditions that preclude study participation

Additional exclusion criteria for the MRI component:

- Contraindications to MRI (e.g., non-MRI-compatible metallic implants or severe claustrophobia)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tapered Maintenance rTMS TBS; Participants receive maintenance theta burst stimulation (TBS) according to a tapered treatment schedule. Following a four-week stimulation-free interval after successful acute TBS, participants receive two sessions per week during weeks 5 to 8 and one session per week during weeks 9 to 20, resulting in a total of 20 maintenance sessions.	Device: Repetitive Transcranial Magnetic Stimulation (rTMS), Theta Burst Stimulation; Participants receive maintenance rTMS treatment (intermittent theta burst stimulation) following successful acute iTBS treatment. Participants are randomized to either a tapered or a clustered maintenance protocol. Both protocols consist of 20 maintenance stimulation sessions delivered over 20 weeks following a four-week stimulation-free interval but differ in the temporal distribution of stimulation sessions.
Experimental: Clustered Maintenance TBS; Participants receive maintenance theta burst stimulation (TBS) according to a clustered treatment schedule. Following a four-week stimulation-free interval after successful acute TBS, participants receive four treatment clusters consisting of five sessions per week (1 session per day) during weeks 5, 10, 15, and 20, resulting in a total of 20 maintenance sessions.	Device: Repetitive Transcranial Magnetic Stimulation (rTMS), Theta Burst Stimulation; Participants receive maintenance rTMS treatment (intermittent theta burst stimulation) following successful acute iTBS treatment. Participants are randomized to either a tapered or a clustered maintenance protocol. Both protocols consist of 20 maintenance stimulation sessions delivered over 20 weeks following a four-week stimulation-free interval but differ in the temporal distribution of stimulation sessions.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to depressive relapse or clinically relevant symptom worsening	Time from randomization to the first occurrence of depressive relapse or clinically relevant symptom worsening during the 24-week follow-up period. Clinically relevant symptom worsening is defined as a transition to a higher depression severity category together with an increase of at least 5 points in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score. Relapse is defined as recurrence of at least moderate depressive symptoms (MADRS ≥20) together with loss of the previously achieved treatment response.	From randomization through Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Montgomery-Åsberg Depression Rating Scale Total Score	Change in depressive symptom severity as assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS). The MADRS total score ranges from 0 to 60, with higher scores indicating greater severity of depressive symptoms.	Baseline and Weeks 4, 8, 12, 16, 20, and 24
Change in Beck Depression Inventory II Total Score	Change in patient-reported depressive symptom severity as assessed using the Beck Depression Inventory II Scale. Higher total scores indicate greater severity of depressive symptoms.	Baseline and Weeks 4, 8, 12, 16, 20, and 24
Change in Global Assessment of Functioning Score (GAF)	Change in psychosocial functioning as assessed using the Global Assessment of Functioning scale. Scores range from 0 to 100, with lower scores indicating greater impairment in psychosocial functioning.	Baseline and Weeks 4, 8, 12, 16, 20, and 24
Change in Clinical Global Impression Score (CGI)	Change in global clinical status as assessed using the Clinical Global Impression scale.	Baseline and Weeks 4, 8, 12, 16, 20, and 24
Change in Resting-State Functional Connectivity	Change in resting-state functional connectivity derived from functional magnetic resonance imaging.	During Maintenance rtMS Week 0-24
Change in Cerebral Perfusion Measured by Arterial Spin Labeling	Change in cerebral perfusion parameters derived from arterial spin labeling magnetic resonance imaging.	During maintenance treatment week 0-24
Change in Diffusion MRI Measures of Structural Connectivity and Microstructure	Change in structural connectivity and tissue microstructure measures derived from diffusion imaging, including neurite orientation dispersion and density imaging.	during maintenance treatment week 0 to 24
Change in Quantitative MRI Parameters	Change in quantitative magnetic resonance imaging parameters, including T1 mapping, T2 mapping, and magnetization transfer mapping.	During maintenance treatment week 0-24

Collaborators and Investigators

• Sponsor: Technical University of Munich
• Collaborators: Medizinische Universitätsklinik Tübingen

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): September 30, 2028
• Study Completion (Estimated): September 30, 2028

Study Registration Dates

• First Submitted: July 21, 2026
• First Submitted That Met QC Criteria: July 21, 2026
• First Posted (Actual): July 27, 2026

Study Record Updates

• Last Update Posted (Actual): July 27, 2026
• Last Update Submitted That Met QC Criteria: July 21, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: MDD; NIBS; MaintenanceTMS; TaperingTMS; ClusterTMS; DepressiveSyndrome
• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Depressive Disorder; Depressive Disorder, Major; Therapeutics; Magnetic Field Therapy; Transcranial Magnetic Stimulation
• Other Study ID Numbers: VISIONS25-MU5; 2026-187-S-CT (Other Identifier: Ethics Committee of the Technical University of Munich)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: A decision regarding the sharing of individual participant data has not yet been made.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No