Major Depressive DisorderEarly-TMSNCT06545474
Effects of rTMS Compared to SSRI as Early Treatment of Depression (Early-TMS)
A study testing bilateral theta burst stimulation and SSRI treatment in people with Major Depressive Disorder, run by University Hospital Tuebingen.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- bilateral theta burst stimulation and SSRI treatment
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 106 participants
- Where
- No sites listed yet
- Study dates
- 15 Sep 2024to 31 Dec 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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;
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- 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.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Repetitive Transcranial Magnetic Stimulation (rTMS) as an Early Intervention in Major Depression (MD) Compared to Antidepressant Selective Serotonin Reuptake Inhibitor (SSRI) Medication (Early-TMS)
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.
Read the 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
- Being tested
- bilateral theta burst stimulation, SSRI treatment
- Keywords
- Depression, non-invasive brain stimulation, repetitive transcranial magnetic stimulation, theta burst stimulation, non-treatment resistant depression
- Medical subject headings
- Depressive Disorder, Major, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
bilateral theta burst stimulationDevice
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 treatmentDrug
Participants receive 4 weeks SSRI treatment with escitalopram (10mg/day) as standard drug.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: SSRI treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Aug 2024
- Study start15 Sep 2024 (estimated)
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- More trials run by University Hospital TuebingenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 106 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital Tuebingen
- Sponsor type
- University, hospital or other
- Collaborators
- German Center for Mental Health
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06545474
- Sponsor's protocol ID
- 614/2023BO1
- Acronym
- Early-TMS
- Status last verified
- Aug 2024
- First submitted
- 5 Aug 2024
- Last updated
- 19 Aug 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 39985658
Study at a glance
From the registry record, last updated by the sponsor on 19 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Repetitive Transcranial Magnetic Stimulation (rTMS) as an Early Intervention in Major Depression (MD) Compared to Antidepressant Selective Serotonin Reuptake Inhibitor (SSRI) Medication (Early-TMS)
- ClinicalTrials.gov ID
- NCT06545474
- Acronym / sponsor ID
- Early-TMS / 614/2023BO1
- Conditions
- Major Depressive Disorder
- Keywords
- Depression, non-invasive brain stimulation, repetitive transcranial magnetic stimulation, theta burst stimulation, non-treatment resistant depression
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 106 participants (estimated)
- Lead sponsor
- University Hospital TuebingenUniversity, hospital or other
- Collaborators
- German Center for Mental Health
- Study start
- 15 Sep 2024 (estimated)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 9 Aug 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| theta burst stimulation (TBS) | Experimental | Device: bilateral theta burst stimulationIn 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. |
| SSRI treatment | Active comparator | Drug: SSRI treatmentIn 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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;
Key exclusion criteria (13 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| bilateral theta burst stimulationEach 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. | Device | theta burst stimulation (TBS) |
| SSRI treatmentParticipants receive 4 weeks SSRI treatment with escitalopram (10mg/day) as standard drug. | Drug | SSRI treatment |
Primary outcome
response rates after Stage I
Time frame: 4 weeks
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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Aug 2024.
- Derived from this study: PubMed 39985658Becker-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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Questions about this trial
What is this clinical trial studying?
A study testing bilateral theta burst stimulation and SSRI treatment in people with Major Depressive Disorder, run by University Hospital Tuebingen.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 19 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Christian Plewnia, Prof. Dr. (+4970712984858, christian.plewnia@med.uni-tuebingen.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
response rates after Stage I (time frame: 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06545474, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Aug 2024.