Treatment of Major Depressive Disorder With Bilateral Theta Burst Stimulation
- Conditions
- Major Depressive Disorder
- Interventions
- Device: Transcranial Magnetic StimulationDevice: Sham Transcranial Magnetic Stimulation
- Registration Number
- NCT04392947
- Lead Sponsor
- University Hospital Tuebingen
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 236
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description combined iTBS/cTBS Transcranial Magnetic Stimulation 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. sham stimulation Sham Transcranial Magnetic Stimulation Setup is identical to combined active iTBS/cTBS but TBS is not actively delivered
- Primary Outcome Measures
Name Time Method Response rate of Montgomery-Asberg Depression Rating Scale (MADRS) 6 weeks MADRS reduction of at least 50% of baseline value after end of treatment period between active combined iTBS / cTBS and the sham condition.
(rater questionnaire; MADRS raw score ranges between 0 and 60; the higher the score, the more severe depression)
- Secondary Outcome Measures
Name Time Method Reduction of raw score: Clinical Global Impression (CGI) 6 weeks The reduction of the raw score after treatment will be compared between active TBS and sham TBS (rater questionnaire; score ranges from 0-7; higher score indicates higher level of severity)
Reduction of raw score: Beck Depression Inventory (BDI-II) 10 and 18 weeks The reduction of the raw score during follow-up will be compared between active TBS and sham TBS (self-rating questionnaire; score ranges from 0-63; higher score indicates higher level of severity)
Examination of the influence of Childhood Trauma Questionnaire (CTQ) at baseline as possible predictor for change of MADRS 6 weeks It will be examined whether the CTQ can be used for predicting treatment effect, measured by Montgomery-Asberg Depression Rating Scale (MADRS, see above)
Deterioration rate after treatment period 6 weeks Deterioration is defined as an increase of MADRS (Montgomery-Asberg Depression Rating Scale) score of 25% compared to baseline score (rater questionnaire; range between 0 and 60; higher score indicates higher level of severity)
Work Productivity and Activity Impairment Questionnaire (WPAI) 6 and 18 weeks Functionality will be assessed by Work Productivity and Activity Impairment Questionnaire (WPAI; self-rating questionnaire) at baseline, after treatment period as well as during follow-up; contains 6 questions about the effect of health problems on the ability to work and perform regular activities. Health problems are defined as any physical or emotional problem or symptom. Patients are asked to fill in the blanks or circle a number; there is no overall score;
Reduction of raw score: Hamilton Depression Rating Scale 17 items (HDRS17) 6 weeks The reduction of the raw score after treatment will be compared between active TBS and sham TBS (rater questionnaire; score ranges from 0-53;higher score indicates higher level of severity)
Frequency of adverse events 6 weeks Comparison of both arms in respect to number of adverse events during treatment period
Examination of the influence of cognitive performance at baseline as possible predictor for change of MADRS 6 weeks It will be examined whether cognitive performance measured by THINC-Integrated Tool (Thinc-it -tool; includes 4 different test covering different aspects of cognition) at baseline can be used for predicting treatment effect, measured by Montgomery-Asberg Depression Rating Scale (MADRS, see above)
Remission rate after treatment 6 weeks Montgomery-Asberg Depression Rating Scale (MADRS) \</= 10 after treatment (rater questionnaire; MADRS raw score ranges between 0 and 60; the higher the score, the more severe depression)
Reduction of raw score: Montgomery-Asberg Depression Rating Scale (MADRS) 6 weeks The reduction of the raw score after treatment will be compared between active TBS and sham TBS (rater questionnaire; range between 0 and 60; higher score indicates higher level of severity)
Reduction of raw score: WHO-5 well-being index 10 and 18 weeks The reduction of the raw score during follow-up will be compared between active TBS and sham TBS (self-rating questionnaire; score ranges from 0-25; lower score indicates higher level of severity)
Trial Locations
- Locations (7)
University of Regensburg, Dept. Psychiatry and Psychotherapy
🇩🇪Regensburg, Germany
University of Tuebingen, Dept Psychiatry and Psychotherapy
🇩🇪Tuebingen, Germany
University of Um, Dept. Psychiatry and Psychotherapy
🇩🇪Ulm, Germany
University of Wuerzburg, Dept. Psychiatry and Psychotherapy
🇩🇪Wuerzburg, Germany
University of Munich
🇩🇪Munich, Germany
Department of Psychiatry, Psychotherapy and Psychosomatics, Medical Faculty, University of Augsburg, Bezirkskrankenhaus Augsburg
🇩🇪Augsburg, Germany
University of Leipzig, Dept. Psychiatry and Psychotherapy
🇩🇪Leipzig, Germany