Escitalopram, Placebo and tDCS in Depression: a Non-inferiority Trial

Phase 3

Completed

• Conditions: Major Depressive Disorder; Major Depressive Disorder, Recurrent, Unspecified; Major Depressive Disorder, Single Episode, Unspecified
• Interventions: Device: transcranial direct current stimulation; Drug: Escitalopram oxalate; Other: Sham tDCS + Placebo Pill

• Registration Number: NCT01894815
• Lead Sponsor: University of Sao Paulo

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations
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Related News

Study Timeline

• Study First Submitted: 2013-07-03
• Study First Submitted QC: 2013-07-09
• Study First Posted: 2013-07-10
• Study Start: 2013-10
• Primary Completion: 2016-07
• Study Completion: 2016-11
• Status Verified: 2016-12
• Last Update Submitted: 2016-12-01
• Last Update Posted: 2016-12-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 245

Inclusion Criteria

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

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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).

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Active tDCS / placebo pill	transcranial direct current stimulation	transcranial direct current stimulation, using the parameters specified in Interventions.
Sham tDCS / escitalopram	Escitalopram oxalate	Escitalopram oxalate (Reconter), 10mg/day (first 3 weeks) and 20mg/day (week 3 to week 10).
Sham tDCS / placebo pill	Sham tDCS + Placebo Pill	For sham tDCS, the device is automatically turned off after 30 second of stimulation and remains turned off during the 30-min session. For placebo pill, the pill has the same size, taste and color than escitalopram, and placebo and escitalopram will be provided in identical bottles, differing only according to a random-generated number placed in the label.

Primary Outcome Measures

Name	Time	Method
Changes in Hamilton Rating Scale for Depression, 17 items (HAMD17)	Weeks 0 and 10	Continuous measure (score changes). Non-inferiority assessment: the difference between tDCS to escitalopram should be \>50% of escitalopram to placebo efficacy.

Secondary Outcome Measures

Name	Time	Method
Change in HDRS	Weeks 0, 3, 6, 8, 10	Continuous measure (score changes).
Change in Montgomery-Asberg Depression Rating Scale (MADRS)	Weeks 0, 3, 6, 10	Continuous measure (score changes).
Change in Beck Depression Inventory (BDI)	Weeks 0, 3, 6, 10
Change in Positive and Negative Affect Scale (PANAS)	Weeks 0, 3, 6, 10
Change in State-Trait Anxiety Inventory (STAI)	Weeks 0, 3, 6, 10
Hamilton Rating Scale for Depression, 17 items (HAMD17)	Week 10	Remission (HAMD17 ≤7) at week 10.
Adverse events	Week 3 and Week 10.	Assessment and comparisons of tDCS and drug adverse events. We used a tDCS adverse events questionnaire (Brunoni et al., 2011) and the SAFTEE.
Serious adverse events	Up to Week 10.	Serious adverse events include treatment-emergent hypomania/mania (YMRS\>8), suicide, psychiatric hospitalization and others life-threatening or incapacitant events.
Young Manic Rating Scale (YMRS)	Week 3 and Week 10.	Assessment of treatment-emergent hypomania/mania, defined as YRMS\>8.
Predictor of response	Week 3 and 10	Heart rate variability - RMSSD

Trial Locations

Locations (2)

Hospital Universitário, Universidade de São Paulo; 🇧🇷 São Paulo, Brazil

Institute of Psychiatry, HC-FMUSP; 🇧🇷 São Paulo, SP, Brazil