Major Depressive Disorder
Conditions
Keywords
major depression, theta burst stimulation, dorsolateral prefrontal cortex, randomized, sham-controlled, multicenter
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.
Interventions
DEVICETranscranial Magnetic Stimulation
MagVenture Coil Cool B70 A/P
DEVICESham Transcranial Magnetic Stimulation
MagVenture Coil Cool B70 A/P without TMS being actively delivered
Sponsors
Federal Ministry of Health, Germany
Institute of Clinical Epidemiology and applied Biometry, University Tuebingen, Germany
Center of Clinical Trials, University Tuebingen, Germany
University of Ulm
Department of Psychiatry and Psychotherapy, University Regensburg, Germany
Department of Psychiatry and Psychotherapy, University Wuerzburg, Germany
Department of Psychiatry and Psychotherapy, University Munich (LMU), Germany
Department of Psychiatry and Psychotherapy, University Leipzig, Germany
Department of Psychiatry, Psychotherapy and Psychosomatics, Medical Faculty, University of Augsburg, Bezirkskrankenhaus Augsburg, Germany
University Hospital Tuebingen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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: 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) |
| 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) |
| 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) |
| 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) |
| Frequency of adverse events | 6 weeks | Comparison of both arms in respect to number of adverse events during treatment period |
| 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) |
| 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) |
| 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) |
| 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; |
Countries
Germany
Outcome results
None listed