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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Device: bilateral theta burst stimulation; Drug: SSRI treatment

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 Type: Interventional
• Enrollment (Estimated): 106
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Christian Plewnia, Prof. Dr.; Phone Number: +4970712984858; Email: christian.plewnia@med.uni-tuebingen.de
• Study Contact Backup: Name: Julia Becker-Sadzio, Dr.; Phone Number: +4970712984858; Email: julia.becker-sadzio@med.uni-tuebingen.de

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Device: 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.
Active Comparator: 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.	Drug: SSRI treatment; Participants receive 4 weeks SSRI treatment with escitalopram (10mg/day) as standard drug.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Estimated): September 15, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: August 5, 2024
• First Submitted That Met QC Criteria: August 5, 2024
• First Posted (Actual): August 9, 2024

Study Record Updates

• Last Update Posted (Actual): August 19, 2024
• Last Update Submitted That Met QC Criteria: August 15, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Depression; repetitive transcranial magnetic stimulation; non-invasive brain stimulation; theta burst stimulation; non-treatment resistant depression
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major
• Other Study ID Numbers: 614/2023BO1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No