Effectiveness of rTMS With Double-Cone-Coil in Patients With Major Depression

Study Overview
=================
Brief Summary
-----------------
Repetitive Transcranial Magnetic Stimulation (rTMS) is used to modulate the neuronal excitability in patients with depression. In the present study the investigators will examine whether medial frontal rTMS using a double-cone-coil proves to be superior to conventional high-frequency-rTMS applied to the left-sided prefrontal cortex with a butterfly-coil.

Detailed Description
-----------------
Depression is a common mental disorder that presents with depressed mood, loss of interest, feelings of guilt or low self-worth, disturbed sleep or appetite, low energy levels and poor concentration. These problems can become chronic or recurrent and lead to substantial impairments in an individual's ability to take care of his or her everyday's responsibilities, at its worst, depression can lead to suicide. Depression can be reliably diagnosed in primary care. Antidepressant medications and brief, structured forms of psychotherapy are effective for 60-80% of those affected and can be delivered in primary care. In patients with depression the cerebral metabolism is deranged in some specific areas such as hypoexcitability in frontal cortical areas. High-frequency rTMS of the dorsolateral prefrontal cortex (DLPFC) has been investigated for the treatment of hypoexcitability disorders. Mild antidepressant effects of rTMS applied to the left sided dorsolateral prefrontal cortex (DLPFC) using a standard butterfly coil can possibly be increased by a different stimulation protocol over the medial frontal cortex using a double-cone-coil. First hints to effectiveness of this treatment arise from case reports and therefore need replication and comparability to conventional stimulation protocols. In the present study the investigators will examine whether medial frontal rTMS using a double-cone-coil proves to be more effective to conventional high-frequency-rTMS applied to the left-sided prefrontal cortex with a butterfly-coil.

Official Title
-----------------
Effectiveness of Medial Frontal Repetitive Transcranial Magnetic Stimulation With Double-Cone-Coil in Patients With Major Depression

Conditions
-----------------
Depression

Intervention / Treatment
-----------------
* Device: Medial Frontal rTMS Double-Cone-Coil
* Device: Left DLPFC Butterfly Coil
* Device: Placebo Stimulation


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Episode of depression (unipolar or bipolar)( ICD-10) Female or male between 18 and 70 years old Skills to participate in all study procedures 18 or more points in the Hamilton rating scale or depression Stable antidepressant drugs Written informed consent Exclusion Criteria: Clinically relevant unstable internal or neurological comorbidity Evidence of significant brain malformations or neoplasm, head injury Cerebral vascular events Neurodegenerative disorders affecting the brain or prior brain surgery Metal objects in and around body that can not be removed Pregnancy Alcohol or drug abuse Epilepsy or a pathological EEG Heart pacemaker High dose tranquillizers

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Medial Frontal rTMS Double-Cone-Coil<br>High frequency rTMS ( Alpine Biomed Mag Pro Option) applied over medial superior frontal cortex (supplementary motor cortex) (Brodmann area 6/8),Double-Cone-water-cooled-Coil (2000 Stimuli of 10 Hz each session), 110% motor threshold. | Device: Medial Frontal rTMS Double-Cone-Coil<br>* High frequency rTMS ( Alpine Biomed Mag Pro Option) applied over medial superior frontal cortex (supplementary motor cortex) (Brodmann area 6/8),Double-Cone-water-cooled-Coil (2000 Stimuli of 10 Hz each session), 110% motor threshold.<br>|
| Experimental: Left DLPFC Butterfly Coil<br>High frequency rTMS ( Alpine Biomed Mag Pro Option): 2000 stimuli of 10 Hz over the left DLPFC (each session), Butterfly-water-cooled-Coil, 110% motor threshold. | Device: Left DLPFC Butterfly Coil<br>* High frequency rTMS ( Alpine Biomed Mag Pro Option): 2000 stimuli of 10 Hz over the left DLPFC (each session), Butterfly-water-cooled-Coil, 110% motor threshold.<br>|
| Sham Comparator: Placebo Stimulation<br>Sham Stimulation (Conventional butterfly-coil, angled 45°): left DLPFC continuous rTMS, 10 Hz,2000 Stimuli each session, 110% motor threshold | Device: Placebo Stimulation<br>* Sham Stimulation (conventional butterfly-coil, angled 45°): left DLPFC continuous rTMS, 10 Hz, 2000 Stimuli each session, 110% motor threshold<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in depression severity measured by the 21-item Hamilton Depression Rating Scale (Baseline versus end of treatment/ day 19) |  | Day 19 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the Alertness (Baseline versus end of treatment/ day 19) |  | Day 19 | 
| Number of responders (response = decrease of the Hamilton Depression rating scale for at least 50%) (Baseline versus end of treatment/ day 19) |  | Day 19 | 
| Change in the Beck Depression Inventory (Baseline versus end of treatment/ day 19) |  | Day 19 | 
| Change in the Clinical Global Impression Scale (Baseline versus end of treatment/ day 19) |  | Day 19 | 
| Change in the Global Assessment of Functioning scale (Baseline versus end of treatment/ day 19) |  | Day 19 | 
| Change in the Alertness (Baseline versus follow-up I/ day 47) |  | Day 47 | 
| Change in the Alertness (Baseline versus follow-up II/ day 75) |  | Day 75 | 
| Number of responders (response = decrease of the Hamilton Depression rating scale for at least 50%) (Baseline versus follow-up I/ day 47) |  | Day 47 | 
| Number of responders (response = decrease of the Hamilton Depression rating scale for at least 50%) (Baseline versus follow-up II/ day 75) |  | Day 75 | 
| Change in the Beck Depression Inventory (Baseline versus follow-up I/ day 47) |  | Day 47 | 
| Change in the Beck Depression Inventory (Baseline versus follow-up II/ day 75) |  | Day 75 | 
| Change in the Clinical Global Impression Scale (Baseline versus follow-up I/ day 47) |  | Day 47 | 
| Change in the Clinical Global Impression Scale (Baseline versus follow-up II/ day 75) |  | Day 75 | 
| Change in the Global Assessment of Functioning scale (Baseline versus follow-up I/ day 47) |  | Day 47 | 
| Change in the Global Assessment of Functioning scale (Baseline versus follow-up II/ day 75) |  | Day 75 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Depression, Transcranial magnetic stimulation, rTMS, DLPFC, medial frontal cortex, anterior cingulate complex