A factorial, double-blinded, randomized clinical trial on major depressive disorder using transcranial direct current stimulation

• Grant number: 09/05728-7
• Support Opportunities: Regular Research Grants
• Start date: December 01, 2009
• End date: November 30, 2011
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Felipe Fregni
• Grantee: Felipe Fregni
• Host Institution: Instituto de Psicologia (IP). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Major Depressive Disorder (MDD) is a common mental disorder, with a lifetime prevalence of 15% and an incidence of 5% per year. MDD occurs three times more in women than men, and in most patients the first episode is on the third decade of life. The core symptoms are depressive mood, lost of interest and pleasure in daily activities, and guilt and low self-esteem thoughts. According to the World Health Organization, it 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 commit suicide. On the other hand, despite the enormous advancement of psychopharmacology in the past decades, about 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; in fact, neurophysiologic studies have already showed 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 could 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. We are going to enroll 120 eligible patients of both genders between 21-65 years that do not present active suicidal idealization. The patients will be allocated in 4 groups at random: group A-P - (1) active tDCS and placebo pill; group S-Se - (2) sham- tDCS and sertraline 50mg/day; group A-Se - (3) active tDCS and sertraline 50mg/day and; group S-P - (4) sham- tDCS and placebo pill. Transcranial DCS will be applied in a daily basis for 10 consecutive working days (2 weeks), after that, 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 controlled 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 the treatment of major depression. (AU)

Scientific publications

(10)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

BRUNONI, ANDRE R.; FRAGUAS JUNIOR, RENERIO; KEMP, ANDREW H.; LOTUFO, PAULO A.; BENSENOR, ISABELA M.; FREGNI, FELIPE. Differential improvement in depressive symptoms for tDCS alone and combined with pharmacotherapy: an exploratory analysis from The Sertraline Vs. Electrical Current Therapy For Treating Depression Clinical Study. INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY, v. 17, n. 1, p. 53-61, JAN 2014. (12/20911-5, 09/05728-7)

BRUNONI, ANDRE R.; MACHADO-VIEIRA, RODRIGO; ZARATE, JR., CARLOS A.; VIEIRA, ERICA L. M.; VANDERHASSELT, MARIE-ANNE; NITSCHE, MICHAEL A.; VALIENGO, LEANDRO; BENSENOR, ISABELA M.; LOTUFO, PAULO A.; GATTAZ, WAGNER F.; et al. BDNF plasma levels after antidepressant treatment with sertraline and transcranial direct current stimulation: Results from a factorial, randomized, sham-controlled trial. European Neuropsychopharmacology, v. 24, n. 7, p. 1144-1151, JUL 2014. (09/05728-7)

BRUNONI, ANDRE RUSSOWSKY; SCHESTATSKY, PEDRO; LOTUFO, PAULO ANDRADE; BENSENOR, ISABELA MARTINS; FREGNI, FELIPE. Comparison of blinding effectiveness between sham tDCS and placebo sertraline in a 6-week major depression randomized clinical trial. CLINICAL NEUROPHYSIOLOGY, v. 125, n. 2, p. 298-305, FEB 2014. (12/20911-5, 09/05728-7)

BRUNONI, ANDRE RUSSOWSKY; TORTELLA, GABRIEL; BENSENOR, ISABELA MARTINS; LOTUFO, PAULO ANDRADE; CARVALHO, ANDRE FERRER; FREGNI, FELIPE. Cognitive effects of transcranial direct current stimulation in depression: Results from the SELECT-TDCS trial and insights for further clinical trials. Journal of Affective Disorders, v. 202, p. 46-52, SEP 15 2016. (12/20911-5, 09/05728-7)

BRUNONI, ANDRE R.; VALIENGO, LEANDRO; BACCARO, ALESSANDRA; ZANAO, TAMIRES A.; DE OLIVEIRA, JANAINA F.; GOULART, ALESSANDRA; BOGGIO, PAULO S.; LOTUFO, PAULO A.; BENSENOR, ISABELA M.; FREGNI, FELIPE. The Sertraline vs Electrical Current Therapy for Treating Depression Clinical Study Results From a Factorial, Randomized, Controlled Trial. JAMA PSYCHIATRY, v. 70, n. 4, p. 383-391, APR 2013. (11/00212-2, 09/05728-7)

BRUNONI, ANDRE R.; MACHADO-VIEIRA, RODRIGO; SAMPAIO-JUNIOR, BERNARDO; VIEIRA, ERICA L. M.; VALIENGO, LEANDRO; BENSENOR, ISABELA M.; LOTUFO, PAULO A.; CARVALHO, ANDRE F.; CHO, HYONG JIN; GATTAZ, WAGNER F.; et al. Plasma levels of soluble TNF receptors 1 and 2 after tDCS and sertraline treatment in major depression: Results from the SELECT-TDCS trial. Journal of Affective Disorders, v. 185, p. 209-213, OCT 1 2015. (09/05728-7)

BRUNONI, ANDRE R.; MACHADO-VIEIRA, RODRIGO; ZARATE, JR., CARLOS A.; VIEIRA, ERICA L. M.; VALIENGO, LEANDRO; BENSENOR, ISABELA M.; LOTUFO, PAULO A.; GATTAZ, WAGNER F.; TEIXEIRA, ANTONIO L.. Assessment of non-BDNF neurotrophins and GDNF levels after depression treatment with sertraline and transcranial direct current stimulation in a factorial, randomized, sham-controlled trial (SELECT-TDCS): An exploratory analysis. PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY, v. 56, p. 91-96, JAN 2 2015. (09/05728-7)

BRUNONI, ANDRE R.; MACHADO-VIEIRA, RODRIGO; ZARATE, CARLOS A.; VALIENGO, LEANDRO; VIEIRA, ERICA L. M.; BENSENOR, ISABELA M.; LOTUFO, PAULO A.; GATTAZ, WAGNER F.; TEIXEIRA, ANTONIO L.. Cytokines plasma levels during antidepressant treatment with sertraline and transcranial direct current stimulation (tDCS): results from a factorial, randomized, controlled trial. Psychopharmacology, v. 231, n. 7, p. 1315-1323, APR 2014. (12/20911-5, 09/05728-7)

BRUNONI, ANDRE RUSSOWSKY; KEMP, ANDREW H.; DANTAS, EDUARDO M.; GOULART, ALESSANDRA C.; NUNES, MARIA ANGELICA; BOGGIO, PAULO S.; MILL, JOSE GERALDO; LOTUFO, PAULO A.; FREGNI, FELIPE; BENSENOR, ISABELA M.. Heart rate variability is a trait marker of major depressive disorder: evidence from the sertraline vs. electric current therapy to treat depression clinical study. INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY, v. 16, n. 9, p. 1937-1949, OCT 2013. (09/05728-7)

BRUNONI, ANDRE RUSSOWSKY; VALIENGO, LEANDRO; BACCARO, ALESSANDRA; ZANAO, TAMIRES ARAUJO; DE OLIVEIRA, JANAINA FARIAS; VIEIRA, GISELLY PEREIRA; BUENO, VIVIANE FREIRE; GOULART, ALESSANDRA C.; BOGGIO, PAULO SERGIO; LOTUFO, PAULO ANDRADE; et al. Sertraline vs. ELectrical Current Therapy for Treating Depression Clinical Trial - SELECT TDCS: Design, rationale and objectives. CONTEMPORARY CLINICAL TRIALS, v. 32, n. 1, p. 90-98, JAN 2011. (09/05728-7)