Efficacy Study of Transcranial Direct Current Stimulation to Treat Major Depressive Disorder

Study Overview
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Brief Summary
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The purpose of this study is to determine whether transcranial direct current stimulation is an effective treatment for major depression, when compared (and combined) to sertraline and placebo.

Detailed Description
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Major Depressive Disorder (MDD) is a common mental disorder, with a lifetime prevalence of 15% and an incidence of 5% per year. Its core symptoms include lack of pleasure in daily activities, thoughts of guilt and depressed mood. According to the World Health Organization, MDD is one of the ten most impairing conditions, leading to missing workdays, loss of quality of life and increasing expenses in health care. Besides, about 1% of patients with MDD complete suicide. Moreover, one third of patients with MDD remain depressed after more than two adequate treatments, i.e., they are refractory to conventional antidepressant treatments; also, most treated patients remain with residual symptoms. Therefore, the development of new treatments is necessary. Transcranial direct current stimulation (tDCS) is a novel, promising technique in the study of several neuropsychiatric conditions. Transcranial DCS is a non-invasive brain stimulation method in which a low intensity direct current is applied through the skull, with neurophysiologic studies showing that a considerable amount of electrical current reach the brain tissues, vis-à-vis the specified parameters. Thus, the DC could be applied over brain MDD-related areas, such as the dorsolateral prefrontal cortex, thereby leading to neuroplasticity and MDD treatment. Indeed, some pilot studies showed that tDCS might ameliorate depressive symptoms. However, it is necessary to replicate these findings in larger populations to increase the generalizability of the results and to verify the efficacy of the intervention. Our aim is to perform a double blind, randomized, factorial study comparing tDCS and sertraline for MDD treatment, enrolling 120 eligible patients of both genders between 21-65 years not presenting active suicidal ideation. They will be allocated in 4 groups at random to receive active tDCS or sham and sertraline 50mg/day or placebo. Transcranial DCS will be applied in a daily basis for 10 consecutive working days (2 weeks), after that, the patients will be followed weekly for 6 weeks. Our primary outcome is the depression rating scores at 6 weeks, measured by the Hamilton Depression Rating Scale (HDRS), 17-itens. In conclusion, our purpose is to perform a clinical tDCS study to verify its efficacy in the treatment of MDD in a sample of patients of several levels of severity and refractoriness. Our secondary objectives are also to verify the safety of the intervention as well as to compare tDCMajor Depressive Disorder (MDD) is a common mental disorder, with a lifetime prevalence of 15% and an incidence of 5% per year. Its core symptoms include lack of pleasure in daily activities, thoughts of guilt and depressed mood. According to the World Health Organization, MDD is one of the ten most impairing conditions, leading to missing workdays, loss of quality of life and increasing expenses in health care. Besides, about 1% of patients with MDD complete suicide. Moreover, one third of patients with MDD remain depressed after more than two adequate treatments, i.e., they are refractory to conventional antidepressant treatments; also, most treated patients remain with residual symptoms. Therefore, the development of new treatments is necessary. Transcranial direct current stimulation (tDCS) is a novel, promising technique in the study of several neuropsychiatric conditions. Transcranial DCS is a non-invasive brain stimulation method in which a low intensity direct current is applied through the skull, with neurophysiologic studies showing that a considerable amount of electrical current reach the brain tissues, vis-à-vis the specified parameters. Thus, the DC could be applied over brain MDD-related areas, such as the dorsolateral prefrontal cortex, thereby leading to neuroplasticity and MDD treatment. Indeed, some pilot studies showed that tDCS might ameliorate depressive symptoms. However, it is necessary to replicate these findings in larger populations to increase the generalizability of the results and to verify the efficacy of the intervention. Our aim is to perform a double blind, randomized, factorial study comparing tDCS and sertraline for MDD treatment, enrolling 120 eligible patients of both genders between 21-65 years not presenting active suicidal ideation. They will be allocated in 4 groups at random to receive active tDCS or sham and sertraline 50mg/day or placebo. Transcranial DCS will be applied in a daily basis for 10 consecutive working days (2 weeks), after that, the patients will be followed weekly for 6 weeks. Our primary outcome is the depression rating scores at 6 weeks, measured by the Hamilton Depression Rating Scale (HDRS), 17-itens. In conclusion, our purpose is to perform a clinical tDCS study to verify its efficacy in the treatment of MDD in a sample of patients of several levels of severity and refractoriness. Our secondary objectives are also to verify the safety of the intervention as well as to compare tDCS vs. sertraline and the association of sertraline and tDCS vs. each treatment alone in major depression treatment.

Official Title
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A Factorial, Double-blinded, Randomized Clinical Trial on Major Depressive Disorder Using Transcranial Direct Current Stimulation

Conditions
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Depressive Disorder, Major

Intervention / Treatment
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* Device: transcranial direct current stimulation
* Drug: Sertraline
* Other: double placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Depressive Disorder, Major (SCID) HDRS > 18 Exclusion Criteria: Other axis I disorders, including Bipolar Disorder, Schizophrenia, Substance Abuse Disorders. Any axis II disorders. Any serious/life-threatening axis III disorders, such as Congestive Heart Failure, Pulmonary Obstructive Chronic Disease, Active Neoplasia. Neurological diseases such as Stroke (and Post-Stroke Depression), Dementias and others.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Factorial Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sham stimulation / sertraline<br>In this arm, patients will receive sham stimulation and sertraline 50mg/day. In sham stimulation, the tDCS device is set in the same fashion as the active stimulation, but the device is turned off after one minute of stimulation. | Drug: Sertraline<br>* Patient will receive sertraline 50mg/day.<br>|
| Sham Comparator: Sham stimulation / placebo pill<br>Placebo pills are sugar pills having the same size and shape of the active pills. In sham stimulation, the tDCS device is set in the same fashion as the active stimulation, but the device is turned off after one minute of stimulation. | Other: double placebo<br>* double placebo arm (sham stimulation/placebo pill)<br>|
| Experimental: Active stimulation / Sertraline<br>In active stimulation, the anode is placed over the left dorsolateral prefrontal cortex and the cathode is placed over the right prefrontal cortex. They are located five centimeters ventrally of the primary motor area, which are located five centimeters laterally of the central point of the scalp (which is located on the intersection of the sagittal and median curves). The device will deliver a charge of 2mA for 30 minutes. Patients will receive Sertraline 50mg/day. | Device: transcranial direct current stimulation<br>* Transcranial direct current stimulation will be applied at 2mA, 30 minutes/day, for 10 weekdays consecutively and two extra stimulations at week 4 and 6.<br>Drug: Sertraline<br>* Patient will receive sertraline 50mg/day.<br>|
| Experimental: Active stimulation / placebo pill<br>In active stimulation, the anode is placed over the left dorsolateral prefrontal cortex and the cathode is placed over the right prefrontal cortex. They are located five centimeters ventrally of the primary motor area, which are located five centimeters laterally of the central point of the scalp (which is located on the intersection of the sagittal and median curves). The device will deliver a charge of 2mA for 30 minutes. Placebo pills are sugar pills having the same size and shape of the active pill | Device: transcranial direct current stimulation<br>* Transcranial direct current stimulation will be applied at 2mA, 30 minutes/day, for 10 weekdays consecutively and two extra stimulations at week 4 and 6.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MADRS score |  | repeated-measures | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HDRS-17 score at week 6. |  | week 6 | 
| Remission rate (MADRS<=10) |  | week 6 | 
| MADRS score |  | week 2 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Depressive Disorder, Major