Treatment of Major Depressive Disorder With Bilateral Theta Burst Stimulation (TBS-D)

University Hospital Tuebingen

Status

Completed

Conditions

Major Depressive Disorder

Treatments

Device: Transcranial Magnetic Stimulation

Device: Sham Transcranial Magnetic Stimulation

Study type

Interventional

Funder types

Other

Identifiers

NCT04392947

01KG2003 BMBF

Details and patient eligibility

About

This is a randomized, double-blind, sham-controlled multicenter clinical trial. The aim is to provide evidence for efficacy of TBS in the treatment of patients with major depression. There will be a direct comparison between combined cTBS/iTBS with sham TBS. Overall, 236 patients with major depression will be randomized either to active TBS or sham TBS in a 1:1 ratio. The planned stimulation paradigms will be applied as add-on therapy to standard therapy (antidepressive medication and / or psychotherapy). Patients will receive 30 stimulation sessions in a 6-week treatment period (one session daily from Monday to Friday). Follow up assessments are scheduled 1 and 3 months after end of treatment period.

Enrollment

238 patients

Sex

All

Ages

18 to 70 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

moderate or severe unipolar depression diagnosed according to criteria of Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5)
duration of the current episode must be ≥ 6 weeks and ≤ 2 years
HDRS17 ≥ 18
mild to moderate treatment resistance according to the Antidepressant Treatment History Form [ATHF-SF]. Treatment resistance is defined as having failed at least one but no more than three adequate antidepressant treatments in this episode
stable antidepressive medication 4 weeks before treatment or no antidepressive treatment
no further relevant psychiatric axis-I and/or axis-II disorder except for anxiety disorders (according to DSM-5 and SCID-5-PD)
no comorbid psychotic symptoms
ability to give consent

Exclusion criteria

acute suicidality (MADRS item 10 score > 4)
antiepileptic drugs and/or benzodiazepines corresponding to > 1mg lorazepam / day
history of brain surgery, significant and clinically relevant brain malformation or neoplasm, head injury, stroke, dementia or other neurodegenerative disorder
history of seizures
previous rTMS treatment
lifetime history of non-response to adequate electroconvulsive therapy (minimum of eight treatments)
deep brain stimulation
cardiac pacemakers, intracranial implant, or metal in the cranium
substance dependence or abuse in the past 3 months (with the exception of tobacco)
severe somatic comorbidity as judged by the study physician
pregnancy

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Quadruple Blind

238 participants in 2 patient groups

combined iTBS/cTBS

Active Comparator group

Description:

Combined theta burst stimulation (TBS) of the left (intermittent TBS, iTBS) and right (continuous TBS, cTBS) dorsolateral prefrontal cortex (dlPFC; F3 and F4 according to EEG10/20 system). Each stimulation session will comprise 2 trains of 600 stimuli each applied in bursts of three pulses at 50 Hz given every 200 ms. iTBS will be applied 20 times for 2 s every 10 s. In the same session, stimulation with cTBS will be applied continuously for 40 s. Intensity of iTBS/cTBS will be standardized at 80 % of the resting motor threshold (rMT). Additionally, patients receive an electrical co-stimulation of the forehead. One electrode is fixed to FZ and the 2nd one is either fixed to the left forehead (iTBS) or the right forehead (cTBS), rectangular aligned to the upper edge of the FZ-electrode with a distance of 0.5 cm. Intensity of the co-stimulation is applied with 50% of TBS-intensity.

Treatment:

Device: Transcranial Magnetic Stimulation

sham stimulation

Sham Comparator group

Description:

Setup is identical to combined active iTBS/cTBS but TBS is not actively delivered

Treatment:

Device: Sham Transcranial Magnetic Stimulation