Treatment of Major Depressive Disorder With Bilateral Theta Burst Stimulation

University Hospital Tuebingen238 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

238

Conditions

Major Depressive Disorder

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

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

Locations (7)

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

Augsburg, Germany

University of Leipzig, Dept. Psychiatry and Psychotherapy

Leipzig, Germany

University of Munich

Munich, Germany

University of Regensburg, Dept. Psychiatry and Psychotherapy

Regensburg, Germany

University of Tuebingen, Dept Psychiatry and Psychotherapy

Tübingen, Germany

University of Um, Dept. Psychiatry and Psychotherapy

Ulm, Germany

University of Wuerzburg, Dept. Psychiatry and Psychotherapy

Würzburg, Germany

Outcomes

Primary Outcomes

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

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)

Time frame: 6 weeks

Secondary Outcomes

Remission rate after treatment

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)

Time frame: 6 weeks

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

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)

Time frame: 6 weeks

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

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)

Time frame: 6 weeks

Reduction of raw score: Clinical Global Impression (CGI)

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)

Time frame: 6 weeks

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

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)

Time frame: 10 and 18 weeks

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

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)

Time frame: 10 and 18 weeks

Work Productivity and Activity Impairment Questionnaire (WPAI)

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;

Time frame: 6 and 18 weeks

Frequency of adverse events

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

Time frame: 6 weeks

Deterioration rate after treatment period

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)

Time frame: 6 weeks

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

It will be examined whether the CTQ can be used for predicting treatment effect, measured by Montgomery-Asberg Depression Rating Scale (MADRS, see above)

Time frame: 6 weeks

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

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)

Time frame: 6 weeks