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

NCT ID: NCT01894815

Last Updated: 2016-12-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 245 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-10-31
• Study Completion Date: 2016-11-30

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.

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Active tDCS / placebo pill

transcranial direct current stimulation, using the parameters specified in Interventions.

Group Type: EXPERIMENTAL

transcranial direct current stimulation

Intervention Type: DEVICE

The anode will be applied over the F3 area and the cathode over the F4 area. The current dose is 2mA, current density is 0.8 A/m2. Electrodes will be 5x5cm in size. The investigators will apply 15 daily, consecutive tDCS sessions (excluding weekends) and after that one session per week until the primary endpoint.

Sham tDCS / escitalopram

Escitalopram oxalate (Reconter), 10mg/day (first 3 weeks) and 20mg/day (week 3 to week 10).

Group Type: ACTIVE_COMPARATOR

Escitalopram oxalate

Intervention Type: DRUG

The investigators will use 10mg and 20mg pills. The investigators will up-titrate escitalopram from 10 to 20mg/day according to the patient tolerability. The maximum dose (20mg/day) is sought to be achieved at week 3.

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.

Group Type: PLACEBO_COMPARATOR

Sham tDCS + Placebo Pill

Intervention Type: OTHER

This group receives sham tDCS and placebo pill.

Interventions

Escitalopram oxalate

The investigators will use 10mg and 20mg pills. The investigators will up-titrate escitalopram from 10 to 20mg/day according to the patient tolerability. The maximum dose (20mg/day) is sought to be achieved at week 3.

Intervention Type: DRUG

transcranial direct current stimulation

The anode will be applied over the F3 area and the cathode over the F4 area. The current dose is 2mA, current density is 0.8 A/m2. Electrodes will be 5x5cm in size. The investigators will apply 15 daily, consecutive tDCS sessions (excluding weekends) and after that one session per week until the primary endpoint.

Intervention Type: DEVICE

Sham tDCS + Placebo Pill

This group receives sham tDCS and placebo pill.

Intervention Type: OTHER

Other Intervention Names

Reconter; tDCS - Soterix Medical Device for Clinical Trials

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).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fundação de Amparo à Pesquisa do Estado de São Paulo

OTHER_GOV

Sponsor Role: collaborator

Brain & Behavior Research Foundation

OTHER

Sponsor Role: collaborator

University of Sao Paulo

OTHER

Sponsor Role: lead

Responsible Party

Andre Brunoni

MD, PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Andre R Brunoni, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Sao Paulo

Locations

Hospital Universitário, Universidade de São Paulo

São Paulo, São Paulo, Brazil

Institute of Psychiatry, HC-FMUSP

São Paulo, São Paulo, Brazil

Countries

Brazil

References

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.

Reference Type: DERIVED

PMID: 34048940 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31105027 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 28657871 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 26176930 (View on PubMed)

Related Links

http://www.sin.org.br

Trial information for participants and investigators.

Other Identifiers

FAPESP 2012/20911-5

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

ELECT-TDCS

Identifier Type: -

Identifier Source: org_study_id