Effects of rTMS Compared to SSRI as Early Treatment of Depression (Early-TMS)

NCT06545474 | Not Yet Recruiting DMC

• 1 other identifier: 614/2023BO1
• Study Type: interventional
• Target: 106
• Locations: 0 countries
• Sites: N/A

Brief Summary

The aim of this randomized multicentre phase 2 clinical trial is to compare the effects of rTMS and SSRI medication as early treatment of depression. In this two-stage, therapy response-adapted trial, 106 patients suffering from non-treatment resistant major depression (non-TR MD) will be randomized in Stage I to either 4 weeks bilateral theta burst stimulation (TBS) or 4 weeks antidepressant SSRI medication. The allocation to Stage II occurs therapy response-adapted. Patients receive either a maintenance treatment or a switch to the respective other treatment arm. The primary outcome is the comparison of the two study arms with regard to therapy response measured with the Montgomery-Asberg Depression Rating Scale (MADRS) after 4 weeks at the end of Stage I.

Conditions

Major Depressive Disorder

Keywords

Depression; non-invasive brain stimulation; repetitive transcranial magnetic stimulation; theta burst stimulation; non-treatment resistant depression

Outcome Measures

Primary Outcomes (1)

• response rates after Stage I

  The primary endpoint is the comparison of the two study arms with regard to the number of participants achieving therapy response (reduction of MADRS score ≥ 50%) after 4 weeks at the end of Stage I.

  4 weeks

Study Arms (2)

theta burst stimulation (TBS)

EXPERIMENTAL

In Stage I, participants receive 4-week bilateral theta burst stimulation. Bilateral TBS consists of 20 sessions that are conducted daily from Monday to Friday over a period of 4 weeks. The target regions are the right and left dorsolateral prefrontal cortex (dlPFC). On the left hemisphere, intermittent TBS (iTBS) is applied, which has a stimulating effect on the target region similar to 10 Hz rTMS. On the right dlPFC, continuous TBS (cTBS) is applied, which has an inhibitory effect similar to 1 Hz rTMS.

Device: bilateral theta burst stimulation

SSRI treatment

ACTIVE COMPARATOR

In Stage I, participants receive escitalopram (10mg/day) as standard medication for 4 weeks. In justified individual cases and according to the decision of the study physician, a higher dose or another SSRI can be administered.

Drug: SSRI treatment

Interventions

bilateral theta burst stimulation DEVICE

Each stimulation session consists of 600 stimuli applied in bursts of 3 pulses at 50 Hz, with an interstimulus interval of 200 ms. iTBS is administered 20 times for 2 seconds to the left dlPFC, with an intertrain interval of 8 seconds and cTBS continuously for 40 seconds to the right dlPFC in alternating order.

theta burst stimulation (TBS)

SSRI treatment DRUG

Participants receive 4 weeks SSRI treatment with escitalopram (10mg/day) as standard drug.

SSRI treatment

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• male, female, or diverse gender;
• age between 18 and 65 years;
• moderate to severe MD according to the diagnostic criteria of DSM-5;
• MADRS Score ≥ 20 points;
• the duration of the episode must be at least 2 weeks and not exceed a period of 2 years;
• no previous antidepressant treatment; indication for antidepressant medication;
• patients must be capable of giving informed consent.

You may not qualify if:

• acute suicidal ideation (MADRS item 10 score \> 4);
• presence of psychotic symptoms;
• antiepileptic drugs or benzodiazepines in a dosage equivalent to \> 1 mg Lorazepam/d;
• comorbid Axis I disorder (except anxiety disorders);
• presence of severe, clinically relevant, and predominant comorbid personality disorder;
• treatment resistance defined as the failure of at least one adequate antidepressant treatment attempt in the current or previous depressive episode;
• neurological pre-existing conditions such as severe traumatic brain injury, neoplasms, brain surgery, stroke within the last 3 months, neurodegenerative diseases: epilepsy or history of epileptic seizures;
• cardiac pacemaker (not compatible with MRI);
• intracranial metallic implants;
• previous rTMS treatment;
• deep brain stimulation;
• other severe somatic diseases; pregnancy;
• contraindications for the use of escitalopram.

Sponsors & Collaborators

• University Hospital Tuebingen: lead
• German Center for Mental Health (DZPG; www.dzpg.org): collaborator

Related Publications (1)

• Becker-Sadzio J, Brendel B, Weller S, Bornheimer E, Mehlig U, Padberg F, Vogelmann U, Kammer T, Strube W, Martus P, Fallgatter AJ, Plewnia C. Effectiveness of rTMS compared to SSRI as early treatment of depression - study protocol of a randomized controlled trial (Early-TMS). Eur Arch Psychiatry Clin Neurosci. 2025 Sep;275(6):1839-1849. doi: 10.1007/s00406-025-01975-4. Epub 2025 Feb 22.

  PMID: 39985658 DERIVED

MeSH Terms

Conditions

Depressive Disorder, Major; Depression

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Central Study Contacts

Christian Plewnia, Prof. Dr.

CONTACT

+4970712984858; christian.plewnia@med.uni-tuebingen.de

Julia Becker-Sadzio, Dr.

CONTACT

+4970712984858; julia.becker-sadzio@med.uni-tuebingen.de

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 5, 2024
• First Posted: August 9, 2024
• Study Start: September 15, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: August 19, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share