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

NCT ID: NCT06545474

Last Updated: 2024-08-19

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 106 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-09-15
• Study Completion Date: 2026-12-31

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.

Detailed Description

This is a therapy response-adapted, two-phase, randomized and controlled study. 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 MD in terms of efficacy and tolerability.

Conditions

Major Depressive Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

theta burst stimulation (TBS)

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.

Group Type: EXPERIMENTAL

bilateral theta burst stimulation

Intervention Type: 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.

SSRI treatment

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.

Group Type: ACTIVE_COMPARATOR

SSRI treatment

Intervention Type: DRUG

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

Interventions

bilateral theta burst stimulation

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.

Intervention Type: DEVICE

SSRI treatment

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

German Center for Mental Health (DZPG; www.dzpg.org)

UNKNOWN

Sponsor Role: collaborator

University Hospital Tuebingen

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Central Contacts

Christian Plewnia, Prof. Dr.

Role: CONTACT

christian.plewnia@med.uni-tuebingen.de

+4970712984858

Julia Becker-Sadzio, Dr.

Role: CONTACT

julia.becker-sadzio@med.uni-tuebingen.de

+4970712984858

References

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 Feb 22. doi: 10.1007/s00406-025-01975-4. Online ahead of print.

Reference Type: DERIVED

PMID: 39985658 (View on PubMed)

Other Identifiers

614/2023BO1

Identifier Type: -

Identifier Source: org_study_id