Escitalopram, Placebo and tDCS in Depression: a Non-inferiority Trial
Condition: Major Depressive Disorder; Major Depressive Disorder, Recurrent, Unspecified; Major Depressive Disorder, Single Episode, Unspecified
MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major
Study type: Interventional
Phase: Phase 3

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.
    

Intervention name(s): Escitalopram oxalate; transcranial direct current stimulation; Sham tDCS + Placebo Pill
Intervention type(s): Drug; Device; Other
Intervention description(s): 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.; 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.; This group receives sham tDCS and placebo pill.
Other intervention name(s): Reconter; tDCS - Soterix Medical Device for Clinical Trials
Intervention MeSH terms: Dexetimide; Citalopram; Escitalopram
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: major depressive disorder; major depression; depressive disorder; major depressive episode