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.

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.

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 / Estudo clínico Escitalopram versus Eletroterapia no Tratamento da Depressão (ELECT-TDCS): racional e desenho de estudo de um ensaio de não inferioridade, de três braços, placebo-controlado

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. .

CONTEXTO 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 clínica, uma vez que a ETCC é praticamente isenta de efeitos adversos. Sua facilidade de uso, portabilidade e preço baixo são outras características atraentes para uso na atenção primária e secundária de saúde. A investigação multimodal de biomarcadores também contribuirá para a compreensão dos mecanismos de ação antidepressivos da ETCC. CONCLUSÃO: Os nossos resultados podem introduzir uma nova técnica no arsenal terapêutico do tratamento da depressão. .

The Pursuit of DLPFC: Non-neuronavigated Methods to Target the Left Dorsolateral Pre-frontal Cortex With Symmetric Bicephalic Transcranial Direct Current Stimulation (tDCS).

BACKGROUND: The dose of transcranial direct current stimulation (tDCS) is defined by electrode montage and current, while the resulting brain current flow is more complex and varies across individuals. The left dorsolateral pre-frontal cortex (lDLPFC) is a common target in neuropsychology and neuropsychiatry applications, with varied approaches used to experimentally position electrodes on subjects. OBJECTIVE: To predict brain current flow intensity and distribution using conventional symmetrical bicephalic frontal 1 × 1 electrode montages to nominally target lDLPFC in forward modeling studies. METHODS: Six high-resolution Finite Element Method (FEM) models were created from five subjects of varied head size and an MNI standard. Seven electrode positioning methods, nominally targeting lDLPFC, were investigated on each head model: the EEG 10-10 including F3-F4, F5-F6, F7-8, F9-F10, the Beam F3-System, the 5-5 cm-Rule and the developed OLE-System were evaluated as electrode positioning methods for 5 × 5 cm(2) rectangular sponge-pad electrodes. RESULTS: Each positioning approach resulted in distinct electrode positions on the scalp and variations in brain current flow. Variability was significant, but trends across montages and between subjects were identified. Factors enhancing electric field intensity and relative targeting in lDLPFC include increased inter-electrode distance and proximity to thinner skull structures. CONCLUSION: Brain current flow can be shaped, but not focused, across frontal cortex by tDCS montages, including intensity at lDLPFC. The OLE-system balances lDLPFC targeting and reduced electric field variability, along with clinical ease-of-use.