Treatment of Major Depressive Disorder With Bilateral Theta Burst Stimulation

Treatment of Major Depressive Disorder With Bilateral Theta Burst Stimulation

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.

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