Using Repetitive Transcranial Magnetic Stimulation (rTMS) for the Treatment of Bipolar Depression

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate whether repetitive transcranial magnetic stimulation (rTMS) treatment is an effective adjunct treatment to mood stabilizers and Bupropion.

Official Title
-----------------
Assessing the Efficacy of Left Repetitive Transcranial Magnetic Stimulation (rTMS) as an Adjunctive Treatment to Mood Stabilizers for the Treatment of Bipolar Depression

Conditions
-----------------
Bipolar Disorder

Intervention / Treatment
-----------------
* Drug: Bupropion
* Device: Active Repetitive Transcranial Magnetic Stimulation
* Other: Placebo
* Device: Sham repetitive transcranial magnetic stimulation


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: BD Type I or II subjects diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) in depressed phase. Age 18 to 70. Rating on the Montgomery-Asberg Depression Rating Scale (MADRS) score > 20. Rating on the Beck Depression Inventory (BDI-II) > 20. Rating on the Young Mania Rating Scale (YMRS) < 8. Non-treated new depressive episode, at least 2 weeks in duration. If recently started on an antidepressant other than Wellbutrin, subject must spend at least 4 weeks at a therapeutic dose before entering the study. Lithium and epival (Sodium Valproate) in monotherapy or in combination. Novel antipsychotics can be combined with mood stabilizers for at least 4 weeks at a steady dosage prior to the study. Exclusion Criteria: History of any DSM-IV Axis I diagnosis other than BD Type I or II Presence of any psychotic symptoms, characterized by a score of 3 or more on item 10 of the MADRS, a score of 6 on item 9 of the MADRS, or a score of 6 or more on item 8 of the YMRS Comorbid active dependence or substance abuse (except nicotine) Prior electroconvulsive therapy failure Pacemaker, automatic implantable defibrillator or implantable pump Aneurysm Clip Heart/Vascular Clip Prosthetic Valve Metal Prosthesis Pregnancy (must do a blood β-HCG test to exclude) Metal or metal fragments in the head Personal or Family history of seizure disorder Increased Intracranial pressure History of stroke, meningitis/encephalitis, moderate to severe traumatic brain injury, neurosurgical procedure Pharmacotherapy using any substances not mentioned in the inclusion criteria, except benzodiazepines at an equivalent dose of less than or equal to 1mg/day of lorazepam. Failure of previous Wellbutrin treatment. Mood disorder secondary to a medical condition. Subject currently enrolled in any detoxification program

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Wellbutrin + Lithium a/o Epival + Sham rTMS<br> | Drug: Bupropion<br>* 150mg daily for first week, 300mg daily thereafter for a total of 8 weeks<br>* Other names: Wellbutrin;Device: Sham repetitive transcranial magnetic stimulation<br>* Sham rTMS will also begin their treatment 5 times a week for 4 weeks in junction with pharmacotherapy (Wellbutrin). Sham rTMS will be delivered at a frequency of 10 Hz and stimulation will be applied in 5-second trains with a 20-second inter-train interval, for 30 trains per session.<br>|
| Experimental: Placebo + Lithium a/o Epival + Active rTMS<br> | Device: Active Repetitive Transcranial Magnetic Stimulation<br>* Daily left DLPFC, at 110% motor threshold, with a frequency of 10 Hz. Stimulation will be applied in 5-second trains with a 10-second inter-train interval, for 30 trains per session. This treatment will be provided for the first 4 weeks of the study.<br>Other: Placebo<br>* 150mg daily first week, 300mg daily thereafter for a total of 8 weeks.<br>|
| Experimental: Wellbutrin + Lithium a/o Epival + Active rTMS<br> | Drug: Bupropion<br>* 150mg daily for first week, 300mg daily thereafter for a total of 8 weeks<br>* Other names: Wellbutrin;Device: Active Repetitive Transcranial Magnetic Stimulation<br>* Daily left DLPFC, at 110% motor threshold, with a frequency of 10 Hz. Stimulation will be applied in 5-second trains with a 10-second inter-train interval, for 30 trains per session. This treatment will be provided for the first 4 weeks of the study.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Montgomery-Asberg Depression Rating Scale (MADRS) from baseline at 8 weeks |  | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Beck Depression Inventory (BDI-II) from baseline at 8 weeks |  | 8 weeks | 
| Change in Young Mania Rating Scale (YMRS) from baseline at 8 weeks |  | 8 weeks | 
| Alcohol use disorder identification test (AUDIT Assessment) |  | At intake | 
| Drug abuse screen test (DAST Assessment) |  | At intake | 
| Clinical Global Impression (CGI) & Analog scale |  | 8 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
bipolar disorder, repetitive transcranial magnetic stimulation (rtms), bupropion, lithium a/o Epival