Transcranial Direct Current Stimulation (tDCS) in the Treatment of Major Depressive Disorder (MDD)

Study Overview
=================
Brief Summary
-----------------
The project will investigate the use of a novel neuromodulatory technique, transcranial direct current stimulation (tDCS) in the treatment of patients with major depressive disorder. Hypothesis 1: Active tDCS will improve depressive symptomology to a significantly greater degree than sham treatment. Hypothesis 2: Active tDCS will be well tolerated and free of major side effects.

Detailed Description
-----------------
Major depression is a disorder with major clinical and economic significance locally and internationally. It is a disorder of high prevalence and results in substantial disease burden and health-care costs. Critically, a significant percentage of patients, usually estimated at around 30%, fail to respond to standard treatments (Fitzgerald 2003). Techniques, such as repetitive transcranial magnetic stimulation (rTMS), are being investigated widely for the treatment of this disorder, with considerable success in recent years (Fitzgerald, Benitez et al. 2006; Hasey 2001). However, TMS equipment is expensive and requires specialized application. Additionally, TMS is associated with some side-effects (e.g. seizures). Given that depression occurs in all cultures and countries, there would be considerable value in developing a low-cost, non-invasive technique that can be applied in a wide variety of settings and which has already been shown to have some efficacy in MDD (Boggio et al. 2007). The proposed study will be a randomized, double blind, placebo-controlled (i.e., sham stimulation vs. active tDCS), longitudinal, treatment outcome trial. Individuals with MDD will be randomized to 1 of 2 treatment conditions. These will be: Active 2mA tDCS: in this condition, 1 stimulator will be used with anodal stimulation to the left prefrontal cortex and cathodal stimulation to the right prefrontal cortex. The placement of anodal stimulation is proposed to enhance activity in the left frontal cortex; the cathode aims to reduce activity in the right prefrontal cortex. Sham treatment: the system setup is identical to that of active tDCS, but the stimulator will be turned off after 30 seconds. A total of 15 treatments will be administered to all participants over 3 weeks (one per working day). Individuals will be randomized on a computer-generated list. Clinical raters and patients will be blind to the treatment condition. Clinical ratings well be conducted prior to and after the treatment course (i.e., after 3 weeks). All subjects randomized to sham treatment will be offered active treatment at the end of the acute treatment phase.

Official Title
-----------------
A Double-blind Sham Controlled Trial of Transcranial Direct Current Stimulation (tDCS) in Treating Refractory Major Depressive Disorder (MDD)

Conditions
-----------------
Major Depressive Disorder

Intervention / Treatment
-----------------
* Device: transcranial direct current stimulation (tDCS)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Competent to consent Have a diagnosis of Major Depressive Disorder and are currently experiencing a Major Depressive Episode as confirmed by the SCID-IV Treatment resistant, defined as a failure to achieve a clinical response, or an inability to tolerate, at least two trials of antidepressant medication of sufficient dose for at least 6 weeks Aged 18 to 75. Concomitant medications including: benzodiazepines, mood stabilizers antidepressants and anticholinergics will be allowed. Since carbamazepine has been shown to interfere with the effects of anodal tDCS, potential participants taking it will not be suitable for inclusion in the trial. Exclusion Criteria: DSM-IV history of substance abuse or dependence in the last 6 months A major and/or unstable medical or neurologic illness Currently taking carbamazepine Pregnancy History of seizures.

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active 2mA tDCS<br>The stimulator will be used to deliver anodal stimulation to the left prefrontal cortex and cathodal stimulation to the right prefrontal cortex. The placement of the anode is proposed to enhance activity in the left frontal cortex; the cathode aims to reduce activity in the right prefrontal cortex. | Device: transcranial direct current stimulation (tDCS)<br>* Delivery of mild current to specified brain regions.<br>* Other names: Stimulator CX-6650 (Rolf Schneider Electronics, Germany);|
| Sham Comparator: Sham tDCS<br>The system setup is identical to that of active tDCS; however, the stimulator will be turned off after 30 seconds. | Device: transcranial direct current stimulation (tDCS)<br>* Delivery of mild current to specified brain regions.<br>* Other names: Stimulator CX-6650 (Rolf Schneider Electronics, Germany);|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hamilton Rating Scale for Depression (HAMD), 17-item version | The Hamilton Depression Scale (HAMD) is a clinician administered test measuring the severity of depressive symptoms in adults and children. | Baseline and at 3 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
tDCS, transcranial direct current stimulation, major depression, double-blind, randomized, placebo-controlled, treatment