Magnetic Brain Stimulation for the Treatment of Adult Depression

Study Overview
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Brief Summary
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This study will evaluate the safety and effectiveness of magnetic brain stimulation for the treatment of major depression in depressed adults with moderate treatment resistance.

Detailed Description
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Major depression is a type of depression that can interfere with the ability to work, study, sleep, eat, and enjoy once pleasurable activities. Because people often develop resistances to medications used to treat depression, new treatments are needed. Decreased electrical activity in the prefrontal region of the brain has been linked to some symptoms of depression. Repetitive transcranial magnetic stimulation (rTMS) can be used to influence the brain's electrical activity. This procedure entails attaching electrodes to the head and using a device to pass magnetic energy through coils and into the brain. rTMS has been shown to have antidepressant effects in depressed individuals. However, optimal levels of intensity and treatment duration have yet to be determined. This study will assess the safety and effectiveness of rTMS on the prefrontal region of the brain in depressed adults with moderate treatment resistance. The treatment phase of this double-blind study will last a minimum of 32 weeks and will consist of 3 phases. In Phase I, participants will be randomly assigned to receive either rTMS or sham stimulation. The sham stimulation will mimic the sensation of rTMS but will not induce an intracerebral current. Treatments will be administered daily for 3 weeks. Participants who show signs of improvement may continue Phase I for up to 3 additional weeks. In Phase II, participants who were unresponsive to Phase I treatment will receive daily rTMS at a lower dose for 3 weeks. Participants who show signs of improvement, but have not achieved remission, may continue Phase II for 4 additional weeks. Baseline magnetic resonance images will be used to determine the optimal stimulus intensity by adjusting for individual differences in cortical to skull distances. Phase III participants will be only those who achieved remission in the first 2 phases. These participants will receive antidepressant medication treatment daily for six months. Participants' functional status and symptoms of depression will be measured using self-report scales and video-recorded interviews at study start date and at the end of each treatment phase.

Official Title
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Optimization of Transcranial Magnetic Stimulation (TMS) for Depression

Conditions
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Depression

Intervention / Treatment
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* Procedure: Prefrontal rTMS
* Drug: Antidepressant Regimen
* Procedure: Sham Stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of major depression with a current episode Hamilton Rating Scale for Depression score higher than 20 No response or intolerance to antidepressant medication in the current depressive episode Exclusion Criteria: Current use of antidepressants Diagnosis of psychosis or anxiety disorder Current substance abuse Seizures or history of head trauma

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active prefrontal rTMS phase1<br>Phase I participants receiving rTMS | Procedure: Prefrontal rTMS<br>* Participants receive 120% motor threshold (MT) over left and right prefrontal cortex. Treatments will be administered daily for 3 weeks. Participants who show signs of improvement may continue Phase I for up to 3 additional weeks.<br>* Other names: rTMS;|
| Placebo Comparator: Sham rTMS phase 1<br>Phase I participants receiving sham stimulation | Procedure: Sham Stimulation<br>* The sham stimulation will mimic the sensation of rTMS but will not induce an intracerebral current. Treatments will be administered daily for 3 weeks.<br>|
| Experimental: rTMS extension<br>rTMS. Phase II participants, all of whom did not meet remission requirements after phase 1. They all receive active open label rTMS | Procedure: Prefrontal rTMS<br>* Participants receive 120% motor threshold (MT) over left and right prefrontal cortex. Treatments will be administered daily for 3 weeks. Participants who show signs of improvement may continue Phase I for up to 3 additional weeks.<br>* Other names: rTMS;|
| Experimental: Open label antidepressant regimen<br>All patients who met remission who were then transitioned to medications after the TMS trial was completed. | Drug: Antidepressant Regimen<br>* Particpants who acheive remission with rTMS may start antidepressant medication in phase III.<br>* Other names: medication;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Depression Remission, as Measured by the Hamilton Rating Scale for Depression | The Hamilton Rating Scale for Depression 17-item total score ranges from 0 to 52 with higher scores indicating more depression. Remission is defined as a total score of ≤ 8 | Measured at the end of Phases 1, 2, and 3 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Electric Stimulation, Magnetic Stimulation, Prefrontal Cortex, Brain