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

Abstract

CONTEXT AND OBJECTIVE: Major depressive disorder (MDD) is a common psychiatric condition, mostly treated with antidepressant drugs, which are limited due to refractoriness and adverse effects. We describe the study rationale and design of ELECT-TDCS (Escitalopram versus Electric Current Therapy for Treating Depression Clinical Study), which is investigating a non-pharmacological treatment known as transcranial direct current stimulation (tDCS). DESIGN AND SETTING: Phase-III, randomized, non-inferiority, triple-arm, placebo-controlled study, ongoing in São Paulo, Brazil. METHODS: ELECT-TDCS compares the efficacy of active tDCS/placebo pill, sham tDCS/escitalopram 20 mg/day and sham tDCS/placebo pill, for ten weeks, randomizing 240 patients in a 3:3:2 ratio, respectively. Our primary aim is to show that tDCS is not inferior to escitalopram with a non-inferiority margin of at least 50% of the escitalopram effect, in relation to placebo. As secondary aims, we investigate several biomarkers such as genetic polymorphisms, neurotrophin serum markers, motor cortical excitability, heart rate variability and neuroimaging. RESULTS: Proving that tDCS is similarly effective to antidepressants would have a tremendous impact on clinical psychiatry, since tDCS is virtually devoid of adverse effects. Its ease of use, portability and low price are further compelling characteristics for its use in primary and secondary healthcare. Multimodal investigation of biomarkers will also contribute towards understanding the antidepressant mechanisms of action of tDCS. CONCLUSION: Our results have the potential to introduce a novel technique to the therapeutic arsenal of treatments for depression. CLINICAL TRIAL REGISTRATION: ClinicalTrials.Gov NCT01894815. RESUMOCONTEXTO E OBJETIVO: O transtorno depressivo maior (TDM) é uma condição psiquiátrica comum, tratada com medicamentos antidepressivos, os quais são limitados devido à refratariedade e efeitos adversos. Descrevemos o racional e o desenho do Estudo Clínico Escitalopram versus Eletroterapia no Tratamento da Depressão (ELECT-TDCS), que investiga um tratamento não farmacológico, conhecido como estimulação transcraniana por corrente contínua (ETCC). DESENHO E LOCAL: Ensaio de fase III, randomizado, de não inferioridade, de três braços, placebo-controlado, em execução em São Paulo, Brasil. MÉTODOS: O estudo compara a eficácia da ETCC ativa/pílula placebo, ETCC simulada/escitalopram 20 mg/dia e ETCC simulada/pílula placebo durante 10 semanas, randomizando 240 pacientes em uma proporção 3:3:2, respectivamente. O objetivo principal é demostrar que a ETCC não é inferior ao escitalopram com uma margem de não inferioridade de pelo menos 50% do efeito de escitalopram em relação ao placebo. Como objetivos secundários, investigamos biomarcadores como polimorfismos genéticos, marcadores séricos, excitabilidade cortical motora, variabilidade da frequência cardíaca e neuroimagem. RESULTADOS: Provar que ETCC é igualmente eficaz a antidepressivos teria um tremendo impacto na psiquiatria clíni-ca...

The Role of the Frontal and Parietal Cortex in Proactive and Reactive Inhibitory Control: A Transcranial Direct Current Stimulation Study

“…Nevertheless, tDCS is a relatively crude method with low spatial specificity. There exist some computational models that can simulate the current flow in the brain (Brunoni et al, 2015;Woods, Bryant, Sacchetti, Gervits, & Hamilton, 2015;Kuo et al, 2013;CaparelliDaquer et al, 2012;Dmochowski, Datta, Bikson, Su, & Parra, 2011), but they need to be verified with experimental methods. In addition, a combination of tDCS and functional imaging can help to better elucidate the neural mechanisms underlying the stimulation effect.…”

Evidence for increased motor cortical facilitation and decreased inhibition in atypical depression

“…The depressed subjects were recruited from an ongoing non‐inferiority, triple‐arm, randomized trial (The Escitalopram vs. Electric Current Therapy for Treating Depression Clinical Study, ELECT‐TDCS, clinicaltrials.gov: NCT01894815) . Certified psychiatrists screened the participants and performed the psychiatric diagnoses based on their clinical expertise and the Portuguese‐translated version of the MINI .…”

Transcranial direct current stimulation (tDCS) for preventing major depressive disorder relapse: Results of a 6-month follow-up

“…The escitalopram versus electrical current therapy for treating depression clinical study (ELECT‐TDCS) study was a randomized, noninferiority, double‐blinded study, in which 245 unipolar depression patients were randomized into three groups: (1) sham tDCS—placebo pill; (2) sham tDCS—escitalopram, and (3) active tDCS—placebo pill. The design (Brunoni et al., ) and results (Brunoni et al., ) of this phase have been previously reported. Briefly, the interventions were 22 sessions of active/sham tDCS (15 sessions once a day for 3 weeks and then once a week until week 10) and verum /placebo escitalopram (10 mg/day for 3 weeks and then 20 mg/day).…”