Clinical trial NCT01894815: Escitalopram, Placebo and tDCS in Depression: a Non-inferiority Trial
Official title: Escitalopram and Transcranial Direct Current Stimulation in Major Depressive Disorder: a Double-blind, Placebo-controlled, Randomized, Non-inferiority Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Major Depressive Disorder
Major Depressive Disorder, Recurrent, Unspecified
Major Depressive Disorder, Single Episode, Unspecified
Keywords: major depressive disorder
major depression
depressive disorder
major depressive episode
Lead sponsor: University of Sao Paulo
Sponsor class: OTHER
Collaborators: name: Fundação de Amparo à Pesquisa do Estado de São Paulo
name: Brain & Behavior Research Foundation
First posted: 2013-07-10
Enrollment: 245
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Major depressive disorder (MDD) is a common psychiatric condition, mostly treated with antidepressant drugs, which are limited for issues such as refractoriness and adverse effects. In this context, the investigators investigate a non-pharmacological treatment known as transcranial direct current stimulation (tDCS). To prove that tDCS is similarly effective than antidepressants would have a tremendous impact in clinical psychiatry, since tDCS is virtually absent of adverse effects. Its ease of use, portability and low price are also interesting characteristics for using in primary and secondary health care. Thus, our aim is to compare tDCS against a fully dosed, effective antidepressant. The study will be a non-inferiority, randomized, double-blinded, placebo-controlled, three-arm trial comparing active tDCS/placebo pill, sham tDCS/escitalopram 20mg/day and sham tDCS/placebo pill. Our primary aim is to show that tDCS is not inferior to escitalopram 20mg/day with a noninferiority margin of at least 50% of the escitalopram-placebo effect.

Detailed description: Major depressive disorder (MDD) is a common psychiatric condition, mostly treated with antidepressant drugs, which are limited for issues such as refractoriness and adverse effects. In this context, the researchers investigate a non-pharmacological treatment known as transcranial direct current stimulation (tDCS). In a prior clinical trial with 120 patients with MDD, the investigators demonstrated that the combination of tDCS with sertraline 50mg/day had increased, faster effects on depressive symptoms (Brunoni et al., JAMA Psychiatry, 2013). However, although the investigators suggested that tDCS vs. sertraline had similar efficacy, such comparison was compromised due to the low sertraline dose and also because the comparison of sertraline vs. placebo was not significant. To prove that tDCS is similarly effective than antidepressants would have a tremendous impact in clinical psychiatry, since tDCS is virtually absent of adverse effects. Its ease of use, portability and low price are also interesting characteristics for using in primary and secondary health care. Thus, our aim is to compare tDCS against a fully dosed, effective antidepressant. The study will be a non-inferiority, randomized, double-blinded, placebo-controlled, three-arm trial comparing active tDCS/placebo pill, sham tDCS/escitalopram 20mg/day and sham tDCS/placebo pill for ten weeks, randomizing 240 patients with MDD in a 3:3:2 ratio (less to placebo). Our primary aim is to show that tDCS is not inferior to escitalopram 20mg/day with a noninferiority margin of at least 50% of the escitalopram-placebo effect. As secondary aims, the researchers will investigate putative biomarkers for tDCS response. This is important considering the large sample size of this study and also the paucity of tDCS studies - therefore, the identification of such biomarkers could generate new hypothesis for future studies and for tDCS' mechanisms of action. The biomarkers will be: genetic polymorphisms (BDNF, SLC6A4, THP1, 5HT2A); serum markers (BDNF); motor cortical excitability (cortical silent period, intracortical inhibition, intracortical facilitation); heart rate variability; and neuroimaging (structural volume of the dorsolateral prefrontal and anterior cingulate cortex, white matter tracts of the prefrontal cortex and posterior cingulate cortex connectivity). This project represents a novel research line in our Institution, and the investigators thereby propose the onset of a new center denominated C.I.N.A. (Interdisciplinary Center for Applied Neuromodulation) that will foment the use and development of projects using neuromodulation techniques. This new center will also interact with other centers on the fields of clinical research, neurosciences and neuropsychiatry.

Eligibility criteria: Inclusion Criteria:

* HAMD17\>=17
* more than 8 years of schooling OR able to read, speak and understand the Portuguese language.
* Low suicide risk.

Exclusion Criteria:

* Bipolar disorders.
* Schizophrenia and other psychotic disorders.
* Anxiety disorders, if it is the primary diagnosis (comorbidity with depression is not an exclusion disorder)
* Substance abuse or dependence.
* Depression symptoms better explained by medical conditions.
* Neurologic conditions (e.g., stroke, multiple sclerosis, brain tumor).
* Severe medical conditions.
* Pregnancy/breast-feeding.
* Severe suicidal ideation, suicidal planning or recent (\<4 weeks) suicide attempt.
* Contra-indications to escitalopram.
* Current use of escitalopram in the current depressive episode.
* Use of escitalopram in a prior depressive episode that was not effective.
* Contra-indications to tDCS.
* Previous use of tDCS (current or previous depressive episode).

Primary outcomes:
measure: Changes in Hamilton Rating Scale for Depression, 17 items (HAMD17)
timeFrame: Weeks 0 and 10
Secondary outcomes:
measure: Change in HDRS
timeFrame: Weeks 0, 3, 6, 8, 10
measure: Change in Montgomery-Asberg Depression Rating Scale (MADRS)
timeFrame: Weeks 0, 3, 6, 10
measure: Change in Beck Depression Inventory (BDI)
timeFrame: Weeks 0, 3, 6, 10
measure: Change in Positive and Negative Affect Scale (PANAS)
timeFrame: Weeks 0, 3, 6, 10
measure: Change in State-Trait Anxiety Inventory (STAI)
timeFrame: Weeks 0, 3, 6, 10
measure: Hamilton Rating Scale for Depression, 17 items (HAMD17)
timeFrame: Week 10
measure: Hamilton Rating Scale for Depression, 17 items (HAMD17)
timeFrame: Week 10
measure: Adverse events
timeFrame: Week 3 and Week 10.
measure: Serious adverse events
timeFrame: Up to Week 10.
measure: Young Manic Rating Scale (YMRS)
timeFrame: Week 3 and Week 10.
measure: Predictor of response
timeFrame: Week 10
measure: Predictor of response
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timeFrame: Week 3 and 10
measure: Predictor of response
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measure: Predictor of response
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timeFrame: Week 3 and 10
measure: Predictor of response
timeFrame: Week 3 and 10
measure: Predictor of response
timeFrame: Week 3 and 10
Other outcomes:
Locations:
city: São Paulo
country: Brazil
facility: Institute of Psychiatry, HC-FMUSP
state: SP
city: São Paulo
country: Brazil
facility: Hospital Universitário, Universidade de São Paulo
Study officials:
affiliation: University of Sao Paulo
name: Andre R Brunoni, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Goerigk SA, Padberg F, Chekroud A, Kambeitz J, Buhner M, Brunoni AR. Parsing the antidepressant effects of non-invasive brain stimulation and pharmacotherapy: A symptom clustering approach on ELECT-TDCS. Brain Stimul. 2021 Jul-Aug;14(4):906-912. doi: 10.1016/j.brs.2021.05.008. Epub 2021 May 26.
citation: Bulubas L, Padberg F, Bueno PV, Duran F, Busatto G, Amaro E Jr, Bensenor IM, Lotufo PA, Goerigk S, Gattaz W, Keeser D, Brunoni AR. Antidepressant effects of tDCS are associated with prefrontal gray matter volumes at baseline: Evidence from the ELECT-TDCS trial. Brain Stimul. 2019 Sep-Oct;12(5):1197-1204. doi: 10.1016/j.brs.2019.05.006. Epub 2019 May 8.
citation: Brunoni AR, Moffa AH, Sampaio-Junior B, Borrione L, Moreno ML, Fernandes RA, Veronezi BP, Nogueira BS, Aparicio LVM, Razza LB, Chamorro R, Tort LC, Fraguas R, Lotufo PA, Gattaz WF, Fregni F, Bensenor IM; ELECT-TDCS Investigators. Trial of Electrical Direct-Current Therapy versus Escitalopram for Depression. N Engl J Med. 2017 Jun 29;376(26):2523-2533. doi: 10.1056/NEJMoa1612999.
citation: Brunoni AR, Sampaio-Junior B, Moffa AH, Borrione L, Nogueira BS, Aparicio LV, Veronezi B, Moreno M, Fernandes RA, Tavares D, Bueno PV, Seibt O, Bikson M, Fraguas R, Bensenor IM. The Escitalopram versus Electric Current Therapy for Treating Depression Clinical Study (ELECT-TDCS): rationale and study design of a non-inferiority, triple-arm, placebo-controlled clinical trial. Sao Paulo Med J. 2015 May-Jun;133(3):252-63. doi: 10.1590/1516-3180.2014.00351712. Epub 2015 Jun 1.