Escitalopram, Placebo and tDCS in Depression: a Non-inferiority Trial (ELECT-TDCS)

Primary Outcome Measures:

• Changes in Hamilton Rating Scale for Depression, 17 items (HAMD17) [ Time Frame: 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:

• Change in HDRS [ Time Frame: Weeks 0, 3, 6, 8, 10 ]
  Continuous measure (score changes).
  
  
• Change in Montgomery-Asberg Depression Rating Scale (MADRS) [ Time Frame: Weeks 0, 3, 6, 10 ]
  Continuous measure (score changes).
  
  
• Change in Beck Depression Inventory (BDI) [ Time Frame: Weeks 0, 3, 6, 10 ]
  
• Change in Positive and Negative Affect Scale (PANAS) [ Time Frame: Weeks 0, 3, 6, 10 ]
  
• Change in State-Trait Anxiety Inventory (STAI) [ Time Frame: Weeks 0, 3, 6, 10 ]
  
• Hamilton Rating Scale for Depression, 17 items (HAMD17) [ Time Frame: Week 10 ]
  Response (≥50% improvement from week 0 to 10)
  
  
• Hamilton Rating Scale for Depression, 17 items (HAMD17) [ Time Frame: Week 10 ]
  Remission (HAMD17 ≤7) at week 10.
  
  
• Adverse events [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: Week 3 and Week 10. ]
  Assessment of treatment-emergent hypomania/mania, defined as YRMS>8.
  
  
• Predictor of response [ Time Frame: Week 10 ]
  Age (years)
  
  
• Predictor of response [ Time Frame: Week 10 ]
  Gender
  
  
• Predictor of response [ Time Frame: Week 10 ]
  Low wage (less than 5 monthly wages in Brazil)
  
  
• Predictor of response [ Time Frame: Week 10 ]
  Recurrent depression
  
  
• Predictor of response [ Time Frame: Week 10 ]
  Chronic depression
  
  
• Predictor of response [ Time Frame: Week 10 ]
  Refractory depression
  
  
• Predictor of response [ Time Frame: Week 10 ]
  Severe depression
  
  
• Predictor of response [ Time Frame: Week 10 ]
  Benzodiazepine use
  
  
• Predictor of response [ Time Frame: Week 10 ]
  Higher education (>15 years of schooling)
  
  
• Predictor of response [ Time Frame: Week 10 ]
  Age of onset of the depressive episode (years)
  
  
• Predictor of response [ Time Frame: Week 10 ]
  Any anxiety disorder
  
  
• Predictor of response [ Time Frame: Week 10 ]
  Physical activity
  
  
• Predictor of response [ Time Frame: Week 10 ]
  melancholic depression
  
  
• Predictor of response [ Time Frame: Week 10 ]
  atypical depression
  
  
• Predictor of response [ Time Frame: Week 10 ]
  smoking status
  
  
• Predictor of response [ Time Frame: Week 10 ]
  hypertension
  
  
• Predictor of response [ Time Frame: Week 10 ]
  diabetes mellitus
  
  
• Predictor of response [ Time Frame: Week 10 ]
  ethnicity
  
  
• Predictor of response [ Time Frame: Week 10 ]
  marital status
  
  
• Predictor of response [ Time Frame: Week 10 ]
  employment status
  
  
• Predictor of response [ Time Frame: Week 10 ]
  obesity
  
  
• Predictor of response [ Time Frame: Week 10 ]
  familial psychiatry history
  
  
• Predictor of response [ Time Frame: Week 10 ]
  Temperament and Character Inventory - Novelty seeking
  
  
• Predictor of response [ Time Frame: Week 10 ]
  Any tDCS related adverse event.
  
  
• Predictor of response [ Time Frame: Week 10 ]
  Temperament and Character Inventory - Harm avoidance
  
  
• Predictor of response [ Time Frame: Week 10 ]
  Temperament and Character Inventory - Reward Dependence
  
  
• Predictor of response [ Time Frame: Week 10 ]
  Temperament and Character Inventory - Persistence
  
  
• Predictor of response [ Time Frame: Week 10 ]
  Temperament and Character Inventory - Cooperativeness
  
  
• Predictor of response [ Time Frame: Week 10 ]
  Temperament and Character Inventory - Self-transcendence
  
  
• Predictor of response [ Time Frame: Week 10 ]
  Temperament and Character Inventory - Self-directedness
  
  
• Predictor of response [ Time Frame: Week 10 ]
  FAS verbal fluency test
  
  
• Predictor of response [ Time Frame: Week 10 ]
  Digit span forward
  
  
• Predictor of response [ Time Frame: Week 10 ]
  Digit span backward
  
  
• Predictor of response [ Time Frame: Week 10 ]
  Trail Making Test - A
  
  
• Predictor of response [ Time Frame: Week 10 ]
  Trail Making Test - B
  
  
• Predictor of response [ Time Frame: Week 10 ]
  Symbol digit
  
  
• Predictor of response [ Time Frame: Week 10 ]
  Montreal Cognitive Assessment
  
  
• Predictor of response [ Time Frame: Week 3 and 10 ]
  Motor Cortical Excitability - Cortical silent period (left and right hemispheres)
  
  
• Predictor of response [ Time Frame: Week 3 and 10 ]
  Motor Cortical Excitability - Intracortical inhibition (left and right hemispheres)
  
  
• Predictor of response [ Time Frame: Week 3 and 10 ]
  Motor Cortical Excitability - Intracortical facilitation (left and right hemispheres)
  
  
• Predictor of response [ Time Frame: Week 3 and 10 ]
  Heart rate variability - HF
  
  
• Predictor of response [ Time Frame: Week 3 and 10 ]
  Heart rate variability - LF
  
  
• Predictor of response [ Time Frame: Week 3 and 10 ]
  Heart rate variability - RMSSD
  
  

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.