Treatment of Major Depressive Disorder With Bilateral Theta Burst Stimulation
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 238
- 试验地点
- 12
- 主要终点
- Response rate of Montgomery-Asberg Depression Rating Scale (MADRS)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
The usage of a special active/placebo (A/P) coil in combination with an electrical co-stimulation will guarantee masking.
A hard cover surrounds the A/P coil and for this reason it is not possible to see which side is the active side of the coil. By entering a randomized code into the stimulator, the operator receive information whether the coil is in the correct position or has to be flipped around. The code does not allow third parties to identify to which study arm a patient has been assigned. The concealment of the assignment remains until the statistical analysis is finished.
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
combined iTBS/cTBS
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.
干预措施: Transcranial Magnetic Stimulation (Device)
sham stimulation
Setup is identical to combined active iTBS/cTBS but TBS is not actively delivered
干预措施: Sham Transcranial Magnetic Stimulation (Device)
结局指标
主要结局
Response rate of Montgomery-Asberg Depression Rating Scale (MADRS)
时间窗: 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)
次要结局
- Reduction of raw score: Clinical Global Impression (CGI)(6 weeks)
- Reduction of raw score: Beck Depression Inventory (BDI-II)(10 and 18 weeks)
- Examination of the influence of Childhood Trauma Questionnaire (CTQ) at baseline as possible predictor for change of MADRS(6 weeks)
- Deterioration rate after treatment period(6 weeks)
- Work Productivity and Activity Impairment Questionnaire (WPAI)(6 and 18 weeks)
- Reduction of raw score: Hamilton Depression Rating Scale 17 items (HDRS17)(6 weeks)
- Frequency of adverse events(6 weeks)
- Examination of the influence of cognitive performance at baseline as possible predictor for change of MADRS(6 weeks)
- Remission rate after treatment(6 weeks)
- Reduction of raw score: Montgomery-Asberg Depression Rating Scale (MADRS)(6 weeks)
- Reduction of raw score: WHO-5 well-being index(10 and 18 weeks)