Major Depressive Disorder
Conditions
Keywords
Depression, non-invasive brain stimulation, repetitive transcranial magnetic stimulation, theta burst stimulation, non-treatment resistant depression
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.
Interventions
DEVICEbilateral 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.
DRUGSSRI treatment
Participants receive 4 weeks SSRI treatment with escitalopram (10mg/day) as standard drug.
Sponsors
German Center for Mental Health (DZPG; www.dzpg.org)
University Hospital Tuebingen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| response rates after Stage I | 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. |
Contacts
Primary ContactChristian Plewnia, Prof. Dr.
Backup ContactJulia Becker-Sadzio, Dr.
Outcome results
None listed