Repetitive Transcranial Magnetic Stimulation in Pharmaco-naïve Patients With Major Depression

Study Overview
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Brief Summary
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Repetitive transcranial magnetic stimulation (rTMS) has become a safe and efficacious treatment for patients with treatment-resistant depression. In several studies investigating the antidepressant efficacy of rTMS, it has been shown that in low treatment-resistant patients rTMS is more efficacious than in patients where several treatment attempts have failed. Albeit this finding, most studies to date primarily recruited patients with relatively high degrees of treatment-resistance and there is a lack of trials investigating rTMS as a first-line treatment. Therefore, this trials aims to compare the antidepressant efficacy of 4 weeks open-label theta-burst TMS in non-treatment-resistant patients with a comparable group of treatment-resistant MDD patients.

Detailed Description
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Repetitive transcranial magnetic stimulation (rTMS) has become a safe and efficacious treatment for patients with treatment-resistant depression (Mutz et al., 2019). Consequently, several countries including Australia, Brazil, Canada, Israel and the United States have approved rTMS as second-line treatment for major depressive disorder (MDD), while others have included rTMS in their guidelines for good clinical practice (e.g. Finland, Germany and Serbia). Historically, rTMS was conceptualized as a soft alternative to electroconvulsive therapy. Therefore, most studies to date primarily recruited patients with relatively high degrees of treatment-resistance (> two failed treatment attempts) and there is a lack of trials investigating rTMS as a first or second line treatment. This finding is contrasted by the fact that on the most stable predictors of response to rTMS is low-treatment resistance. Therefore, this trial aims to compare the antidepressant efficacy of 20 pharmaco-naïve patients with 20 treatment-resistant patients diagnosed with major depressive disorder. In this open label trial, patients will receive four weeks high-frequency left-sided theta burst TMS (lDLFPC). The target will be located by neuronavigation to the target ascertained by Fox et al.

Official Title
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Comparative Efficacy of Repetitive Transcranial Magnetic Stimulation in Pharmaco-naïve and Treatment Resistant Patients With Major Depression

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Device: intermittent theta burst stimulation (iTBS)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant is able to provide consent. Diagnosis of Major Depressive Disorder according to DSM-V criteria. The duration of the current episode is at least four weeks and no more than five years. During the current episode, pharmacological intervention was prescribed (and taken) by the patient Exclusion Criteria: The participant does not fulfill requirements for iTBS treatment according to safety guidelines. Cardiac or neurological surgery, active implants, metal parts within the body, claustrophobia. Pregnancy or breast-feeding. Psychiatric illness, e.g. substance abuse, psychosis, bipolar disorder, anorexia, obsessive compulsive disorder, post-traumatic stress disorder, generalized anxiety disorder, panic disorder, personality disorder. Antipsychotic medication not approved for the treatment of depression. Acute suicidality. Conditions related to increased intracranial pressure. Brain injury or stroke. History of epilepsy in patient or in first-degree relative. Cerebral aneurysm. Neurological illness (e.g. dementia (score of less than 25 in Mini Mental State Exam), Parkinson's disease, chorea huntington, multiple sclerosis). Course of electroconvulsive therapy (ECT) within the last three months

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Non-Treatment Resistant Patients<br> | Device: intermittent theta burst stimulation (iTBS)<br>* 20 sessions of iTBS<br>|
| Treatment-Resistant Patients<br>The group of patients from NCT03944213 | Device: intermittent theta burst stimulation (iTBS)<br>* 20 sessions of iTBS<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in depression severity as measured by the Hamilton Depression Rating Scale (HDRS-17) over 7 timepoints | Remission defined as HDRS-17 score (range: 0 to 52) of less than or equal to 8 after the iTBS course. Response defined as a reduction of at least 50% from baseline in HDRS-17 score after treatment | Six weekly measurements starting 1 week before first iTBS treatment session, one follow-up measurement four weeks after last measurement | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Major Depressive Disorder, rTMS, TBS, Theta Burst Stimulation, Neuronavigation, Non-Treatment Resistant, Pharmaco-Naïve