Clinical trial NCT01033084: Efficacy Study of Transcranial Direct Current Stimulation to Treat Major Depressive Disorder
Official title: A Factorial, Double-blinded, Randomized Clinical Trial on Major Depressive Disorder Using Transcranial Direct Current Stimulation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Depressive Disorder, Major
Keywords: Depressive Disorder, Major
Lead sponsor: University of Sao Paulo
Sponsor class: OTHER
Collaborators: name: Fundação de Amparo à Pesquisa do Estado de São Paulo
First posted: 2009-12-16
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: MADRS score
timeFrame: repeated-measures
Secondary outcomes:
measure: HDRS-17 score at week 6.
timeFrame: week 6
measure: Remission rate (MADRS<=10)
timeFrame: week 6
measure: MADRS score
timeFrame: week 2
Other outcomes:
Locations:
city: Sao Paulo
country: Brazil
facility: University of Sao Paulo
state: SP
Study officials:
affiliation: University of Sao Paulo
name: Andre R Brunoni, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Brunoni AR, Valiengo L, Baccaro A, Zanao TA, de Oliveira JF, Vieira GP, Bueno VF, Goulart AC, Boggio PS, Lotufo PA, Bensenor IM, Fregni F. Sertraline vs. ELectrical Current Therapy for Treating Depression Clinical Trial--SELECT TDCS: design, rationale and objectives. Contemp Clin Trials. 2011 Jan;32(1):90-8. doi: 10.1016/j.cct.2010.09.007. Epub 2010 Sep 18.
citation: Alessandra Baccaro, Andre Russowsky Brunoni, Isabela Martins Bensenor, Felipe Fregni. Hypomanic episode in unipolar depression during transcranial direct current stimulation. Acta Neuropsychiatrica 22(6):316-318, 2010.
citation: Brunoni AR, Kemp AH, Dantas EM, Goulart AC, Nunes MA, Boggio PS, Mill JG, Lotufo PA, Fregni F, Bensenor IM. Heart rate variability is a trait marker of major depressive disorder: evidence from the sertraline vs. electric current therapy to treat depression clinical study. Int J Neuropsychopharmacol. 2013 Oct;16(9):1937-49. doi: 10.1017/S1461145713000497. Epub 2013 Jun 12.
citation: Brunoni AR, Valiengo L, Baccaro A, Zanao TA, de Oliveira JF, Goulart A, Boggio PS, Lotufo PA, Bensenor IM, Fregni F. The sertraline vs. electrical current therapy for treating depression clinical study: results from a factorial, randomized, controlled trial. JAMA Psychiatry. 2013 Apr;70(4):383-91. doi: 10.1001/2013.jamapsychiatry.32.