Skip to main content
OpenTrials
Completed

NCT Number: NCT04392947

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Major Depressive Disorder Depressive Disorder Depressive Disorder, Major Mental Disorders Mood Disorders

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Department of Psychiatry, Psychotherapy and Psychosomatics, Medical Faculty, University of Augsburg, Bezirkskrankenhaus Augsburg, Augsburg, Germany

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Transcranial Magnetic Stimulation

Device

MagVenture Coil Cool B70 A/P

Sham Transcranial Magnetic Stimulation

Device

MagVenture Coil Cool B70 A/P without TMS being actively delivered

Primary outcomes

  1. Response rate of Montgomery-Asberg Depression Rating Scale (MADRS)

    Time frame: 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 outcomes

  1. Remission rate after treatment

    Time frame: 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)

  2. Reduction of raw score: Montgomery-Asberg Depression Rating Scale (MADRS)

    Time frame: 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)

  3. Reduction of raw score: Hamilton Depression Rating Scale 17 items (HDRS17)

    Time frame: 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)

  4. Reduction of raw score: Clinical Global Impression (CGI)

    Time frame: 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)

  5. Reduction of raw score: Beck Depression Inventory (BDI-II)

    Time frame: 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)

  6. Reduction of raw score: WHO-5 well-being index

    Time frame: 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)

  7. Work Productivity and Activity Impairment Questionnaire (WPAI)

    Time frame: 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;

  8. Frequency of adverse events

    Time frame: 6 weeks

    Comparison of both arms in respect to number of adverse events during treatment period

  9. Deterioration rate after treatment period

    Time frame: 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)

  10. Examination of the influence of Childhood Trauma Questionnaire (CTQ) at baseline as possible predictor for change of MADRS

    Time frame: 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)

  11. Examination of the influence of cognitive performance at baseline as possible predictor for change of MADRS

    Time frame: 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)

Sponsors and collaborators

Lead sponsor

University Hospital Tuebingen

Other

Collaborators

  • Center of Clinical Trials, University Tuebingen, Germany
  • Department of Psychiatry and Psychotherapy, University Leipzig, Germany
  • Department of Psychiatry, Psychotherapy and Psychosomatics, Medical Faculty, University of Augsburg, Bezirkskrankenhaus Augsburg, Germany
  • Federal Ministry of Health, Germany
  • Institute of Clinical Epidemiology and applied Biometry, University Tuebingen, Germany
  • Ludwig-Maximilians - University of Munich
  • University of Regensburg
  • University of Ulm
  • University of Wuerzburg

Registry information

Acronym: TBS-D

Important dates

Study start
2020
Primary completion
2025
Study completion
2025
First posted
May 19, 2020
Registry last updated
Sep 17, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.