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Bipolar depression is associated with marked cognitive deficits. Pharmacological treatments for this condition are limited and may aggravate depressive and cognitive symptoms. Therefore, therapeutic interventions that preserve adequate cognitive functioning are necessary. Our previous results demonstrated significant clinical efficacy of transcranial direct current stimulation (tDCS) in the Bipolar Depression Electrical Treatment Trial (BETTER). Here, cognitive outcomes of this study are reported. We randomized 59 patients with bipolar disorder I or II in an acute depressive episode to receive active (12 2 mA, 30-min, anodal-left, cathodal-right prefrontal cortex tDCS sessions) or sham tDCS. Patients were on stable pharmacological regimen for at least 2 weeks. A battery of 12 neuropsychological assessments in five cognitive domains (attention and processing speed, memory, language, inhibitory control, and working memory and executive function) was performed at baseline, after two weeks and at endpoint (week 6). No significant differences between groups over 6 weeks of treatment were observed for any cognitive outcomes. Moreover, no decrease in cognitive performance was observed. Our findings warrant further replication in larger studies. Trial Registration: clinicaltrials.gov Identifier: NCT02152878.

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BACKGROUND: Transcranial direct current stimulation (tDCS) has shown mixed results for depression treatment. OBJECTIVE: To perform a systematic review and meta-analysis of trials using tDCS to improve depressive symptoms. METHODS: A systematic review was performed from the first date available to January 06, 2020 in PubMed, EMBASE, Cochrane Library, and additional sources. We included randomized, sham-controlled clinical trials (RCTs) enrolling participants with an acute depressive episode and compared the efficacy of active versus sham tDCS, including association with other interventions. The primary outcome was the Hedges' g for continuous depression scores; secondary outcomes included odds ratios (ORs) and number needed to treat (NNT) for response, remission, and acceptability. Random effects models were employed. Sources of heterogeneity were explored via metaregression, sensitivity analyses, subgroup analyses, and bias assessment. RESULTS: We included 23 RCTs (25 datasets, 1,092 participants), most (57%) presenting a low risk of bias. Active tDCS was superior to sham regarding endpoint depression scores (k = 25, g = 0.46, 95% confidence interval [CI]: 0.22-0.70), and also achieved superior response (k = 18, 33.3% vs. 16.56%, OR = 2.28 [1.52-3.42], NNT = 6) and remission (k = 18, 19.12% vs. 9.78%, OR = 2.12 [1.42-3.16], NNT = 10.7) rates. Moreover, active tDCS was as acceptable as sham. No risk of publication bias was identified. Cumulative meta-analysis showed that effect sizes are basically unchanged since total sample reached 439 participants. CONCLUSIONS: TDCS is modestly effective in treating depressive episodes. Further well-designed, large-scale RCTs are warranted.

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Objective: Noninvasive brain stimulation (NIBS) techniques, such as transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS), are increasingly being used to treat mental disorders, particularly major depression. The aim of this comprehensive review is to summarize the main advances, limitations, and perspectives of the field. Methods: We searched PubMed and other databases from inception to July 2017 for articles, particularly systematic reviews and meta-analyses, evaluating the use of NIBS in psychiatric disorders. Results: We reviewed the mechanisms of action, safety, tolerability, efficacy, and relevant clinical parameters of NIBS. Repetitive TMS is already an established technique for the treatment of depression, and there is theoretically room for further methodological development towards a high-end therapeutic intervention. In contrast, tDCS is a technically easier method and therefore potentially suitable for wider clinical use. However the evidence of its antidepressant efficacy is less sound, and a recent study found tDCS to be inferior to antidepressant pharmacotherapy. Clinical trials using rTMS for other mental disorders produced mixed findings, whereas tDCS use has not been sufficiently appraised. Conclusion: The most promising results of NIBS have been obtained for depression. These techniques excel in safety and tolerability, although their efficacy still warrants improvement.

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BACKGROUND: The efficacy of transcranial direct current stimulation (tDCS) as a continuation therapy for the maintenance phase of the depressive episode is low and insufficiently investigated in literature. We investigated whether it could be enhanced by using a more intensive treatment regimen compared to previous reports. METHODS: Twenty-four patients (16 with unipolar depression and eight with bipolar depression) who presented acute tDCS response (≥50% depression improvement in the Hamilton Depression Rating Scale [HDRS]) after receiving 15 tDCS sessions were followed for up to 6 months or until relapse, defined as clinical worsening and/or HDRS > 15. Sessions were performed twice a week (maximum of 48 sessions) over 24 weeks. The anode and the cathode were positioned over the left and right dorsolateral prefrontal cortex (2 mA current, 30 min sessions were delivered). We performed Kaplan-Meier survival analysis and Cox proportional hazards ratios to evaluate predictors of relapse. RESULTS: Out of 24 patients, 18 completed the follow-up period. tDCS treatment was well tolerated. The mean survival duration was 17.5 weeks (122 days). The survival rate at the end of follow-up was 73.5% (95% confidence interval, 50-87). A trend (P = 0.09) was observed for lower relapse rates in nontreatment- vs. antidepressant treatment-resistant patients (7.7% vs. 45.5%, respectively). No differences in efficacy between unipolar and bipolar depression were observed. CONCLUSION: An intensive tDCS treatment regimen consisting of sessions twice a week achieved relatively low relapse rates after a 6-month follow up of tDCS responders, particularly for nontreatment-resistant patients.

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OBJECTIVE: Noninvasive brain stimulation (NIBS) techniques, such as transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS), are increasingly being used to treat mental disorders, particularly major depression. The aim of this comprehensive review is to summarize the main advances, limitations, and perspectives of the field. METHODS: We searched PubMed and other databases from inception to July 2017 for articles, particularly systematic reviews and meta-analyses, evaluating the use of NIBS in psychiatric disorders. RESULTS: We reviewed the mechanisms of action, safety, tolerability, efficacy, and relevant clinical parameters of NIBS. Repetitive TMS is already an established technique for the treatment of depression, and there is theoretically room for further methodological development towards a high-end therapeutic intervention. In contrast, tDCS is a technically easier method and therefore potentially suitable for wider clinical use. However the evidence of its antidepressant efficacy is less sound, and a recent study found tDCS to be inferior to antidepressant pharmacotherapy. Clinical trials using rTMS for other mental disorders produced mixed findings, whereas tDCS use has not been sufficiently appraised. CONCLUSION: The most promising results of NIBS have been obtained for depression. These techniques excel in safety and tolerability, although their efficacy still warrants improvement.

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BACKGROUND: Although several studies indicate that placebo response is large to antidepressant pharmacotherapy in major depressive disorder (MDD), no updated meta-analysis has quantified the magnitude of the placebo (sham) response to repetitive transcranial magnetic stimulation (rTMS) in MDD yet. OBJECTIVE: To conduct a systematic review and meta-analysis on this issue in randomized controlled trials (RCTs) involving participants with MDD; and to explore potential moderators. METHODOLOGY: PubMed/MEDLINE, Embase, PsycINFO, and Web of Science electronic databases were searched from inception up to March 15, 2017 for RCTs that investigated the efficacy of any rTMS modality compared to sham intervention in participants with acute depressive episodes. Cochrane Risk of Bias Tool was used to estimate risks. We estimated the placebo effect size (Hedges's g, random-effects model) response using placebo groups baseline and endpoint depressive symptom scores. Meta-regressions have been employed to explore potential moderators of response. RESULTS: Sixty-one studies met eligibility criteria (N=1328; mean age, 47years; 57% females). Placebo response was large (g=0.8, 95% CI=0.65-0.95, p<0.01) regardless of the modality of intervention. Placebo response was directly associated with publication year and depression improvement of the active group, and inversely associated with higher levels of treatment-resistant depression. Other moderators, including gender, age, and stimulator type, were not associated with the outcome. Overall, 24.6%, 67.2%, and 8.2% of studies had an overall low, unclear, and high bias risk, respectively. CONCLUSION: Placebo response in rTMS depression trials was large and associated with depression improvement of the active treatment group. Such result suggests that excluding placebo responders with a run-in phase may not confer advantage since response to 'active' rTMS may decrease as well. Moreover, placebo response may be a component of therapeutic response to rTMS in MDD. In addition, placebo response increase over time could indicate improvement in rTMS trial designs, including better sham rTMS methods.

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Importance: More effective, tolerable interventions for bipolar depression treatment are needed. Transcranial direct current stimulation (tDCS) is a novel therapeutic modality with few severe adverse events that showed promising results for unipolar depression. Objective: To determine the efficacy and safety of tDCS as an add-on treatment for bipolar depression. Design, Setting, and Participants: A randomized, sham-controlled, double-blind trial (the Bipolar Depression Electrical Treatment Trial [BETTER]) was conducted from July 1, 2014, to March 30, 2016, at an outpatient, single-center academic setting. Participants included 59 adults with type I or II bipolar disorder in a major depressive episode and receiving a stable pharmacologic regimen with 17-item Hamilton Depression Rating Scale (HDRS-17) scores higher than 17. Data were analyzed in the intention-to-treat sample. Interventions: Ten daily 30-minute, 2-mA, anodal-left and cathodal-right prefrontal sessions of active or sham tDCS on weekdays and then 1 session every fortnight until week 6. Main Outcomes and Measures: Change in HDRS-17 scores at week 6. Results: Fifty-nine patients (40 [68%] women), with a mean (SD) age of 45.9 (12) years participated; 36 (61%) with bipolar I and 23 (39%) with bipolar II disorder were randomized and 52 finished the trial. In the intention-to-treat analysis, patients in the active tDCS condition showed significantly superior improvement compared with those receiving sham (ßint = -1.68; number needed to treat, 5.8; 95% CI, 3.3-25.8; P = .01). Cumulative response rates were higher in the active vs sham groups (67.6% vs 30.4%; number needed to treat, 2.69; 95% CI, 1.84-4.99; P = .01), but not remission rates (37.4% vs 19.1%; number needed to treat, 5.46; 95% CI, 3.38-14.2; P = .18). Adverse events, including treatment-emergent affective switches, were similar between groups, except for localized skin redness that was higher in the active group (54% vs 19%; P = .01). Conclusions and Relevance: In this trial, tDCS was an effective, safe, and tolerable add-on intervention for this small bipolar depression sample. Further trials should examine tDCS efficacy in a larger sample. Trial Registration: clinicaltrials.gov Identifier: NCT02152878.

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BACKGROUND: Nasal CPAP is the "gold standard" treatment for OSA. However, oronasal masks are frequently used in clinical practice. The aim of this study was to perform a meta-analysis of all randomized and nonrandomized trials that compared nasal vs oronasal masks on CPAP level, residual apnea-hypopnea index (AHI), and CPAP adherence to treat OSA. METHODS: The Cochrane Central Register of Controlled Trials, Medline, and Web of Science were searched for relevant studies in any language with the following terms: "sleep apnea" and "CPAP" or "sleep apnea" and "oronasal mask" or "OSA" and "oronasal CPAP" or "oronasal mask" and "adherence." Studies on CPAP treatment for OSA were included, based on the following criteria: (1) original article; (2) randomized or nonrandomized trials; and (3) comparison between nasal and oronasal CPAP including pressure level, and/or residual AHI, and/or CPAP adherence. RESULTS: We identified five randomized and eight nonrandomized trials (4,563 patients) that reported CPAP level and/or residual AHI and/or CPAP adherence. Overall, the random-effects meta-analysis revealed that as compared with nasal, oronasal masks were associated with a significantly higher CPAP level (Hedges' g, -0.59; 95% CI, -0.82 to -0.37; P < .001) (on average, +1.5 cm H2O), higher residual AHI (Hedges' g, -0.34; 95% CI, -0.52 to -0.17; P < .001) (+2.8 events/h), and a poorer adherence (Hedges' g, 0.50; 95% CI, 0.21-0.79; P = .001) (-48 min/night). CONCLUSIONS: Oronasal masks are associated with a higher CPAP level, higher residual AHI, and poorer adherence than nasal masks. TRIAL REGISTRY: PROSPERO database; No.: CRD42017064584; URL: https://www.crd.york.ac.uk/prospero/.

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BACKGROUND: Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation modality that has been increasingly used for major depressive disorder (MDD) treatment. Although studies in healthy volunteers showed that the technique is well-tolerated, tDCS safety and acceptability have not been sufficiently explored in patients with MDD. METHODS: We collected individual patient data from 6 randomized clinical trials that had been previously identified in a systematic review and meta-analysis. Primary outcomes were safety (rate of adverse events) and acceptability (rate of dropouts). Secondary outcomes were clinical, demographic and treatment predictors of the primary outcomes. RESULTS: Dropout rates between active (8.8%) and sham (12%) groups were not significantly different (OR= 0.7, p=0.38). Adverse event rates between active (73.5%) and sham (68.3%) groups were not significantly different (OR= 1.4, p= 0.23). Higher current densities were associated with lower adverse event rates. LIMITATIONS: Dropout reasons were not systematically reported and adverse events were not collected using questionnaires standardized across studies. CONCLUSIONS: Active tDCS is as acceptable and safe as sham tDCS, as found in randomized clinical trials of MDD.

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OBJECTIVE: To evaluate whether and to which extent skin redness (erythema) affects investigator blinding in transcranial direct current stimulation (tDCS) trials. MATERIAL AND METHODS: Twenty-six volunteers received sham and active tDCS, which was applied with saline-soaked sponges of different thicknesses. High-resolution skin images, taken before and 5, 15, and 30 min after stimulation, were randomized and presented to experienced raters who evaluated erythema intensity and judged on the likelihood of stimulation condition (sham vs. active). In addition, semi-automated image processing generated probability heatmaps and surface area coverage of erythema. Adverse events were also collected. RESULTS: Erythema was present, but less intense in sham compared to active groups. Erythema intensity was inversely and directly associated to correct sham and active stimulation group allocation, respectively. Our image analyses found that erythema also occurs after sham and its distribution is homogenous below electrodes. Tingling frequency was higher using thin compared to thick sponges, whereas erythema was more intense under thick sponges. CONCLUSIONS: Optimal investigator blinding is achieved when erythema after tDCS is mild. Erythema distribution under the electrode is patchy, occurs after sham tDCS and varies according to sponge thickness. We discuss methods to address skin erythema-related tDCS unblinding.

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IMPORTANCE: Although several strategies of repetitive transcranial magnetic stimulation (rTMS) have been investigated as treatment of major depressive disorder (MDD), their comparative efficacy and acceptability is unknown. OBJECTIVE: To establish the relative efficacy and acceptability of the different modalities of rTMS used for MDD by performing a network meta-analysis, obtaining a clinically meaningful treatment hierarchy. DATA SOURCES: PubMed/MEDLINE, EMBASE, PsycInfo, and Web of Science were searched up until October 1, 2016. STUDY SELECTION: Randomized clinical trials that compared any rTMS intervention with sham or another rTMS intervention. Trials performing less than 10 sessions were excluded. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers used standard forms for data extraction and quality assessment. Random-effects, standard pairwise, and network meta-analyses were performed to synthesize data. MAIN OUTCOMES AND MEASURES: Response rates and acceptability (dropout rate). Remission was the secondary outcome. Effect sizes were reported as odds ratios (ORs) with 95% CIs. RESULTS: Eighty-one studies (4233 patients, 59.1% women, mean age of 46 years) were included. The interventions more effective than sham were priming low-frequency (OR, 4.66; 95% CI, 1.70-12.77), bilateral (OR, 3.96; 95% CI, 2.37-6.60), high-frequency (OR, 3.07; 95% CI, 2.24-4.21), θ-burst stimulation (OR, 2.54; 95% CI, 1.07-6.05), and low-frequency (OR, 2.37; 95% CI, 1.52-3.68) rTMS. Novel rTMS interventions (accelerated, synchronized, and deep rTMS) were not more effective than sham. Except for θ-burst stimulation vs sham, similar results were obtained for remission. All interventions were at least as acceptable as sham. The estimated relative ranking of treatments suggested that priming low-frequency and bilateral rTMS might be the most efficacious and acceptable interventions among all rTMS strategies. However, results were imprecise and relatively few trials were available for interventions other than low-frequency, high-frequency, and bilateral rTMS. CONCLUSIONS AND RELEVANCE: Few differences were found in clinical efficacy and acceptability between the different rTMS modalities, favoring to some extent bilateral rTMS and priming low-frequency rTMS. These findings warrant the design of larger RCTs investigating the potential of these approaches in the short-term treatment of MDD. Current evidence cannot support novel rTMS interventions as a treatment for MDD. TRIAL REGISTRATION: clinicaltrials.gov Identifier: PROSPERO CRD42015019855.

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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.

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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. .

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Dorsolateral prefrontal cortex (DLPFC) hypoactivity and subcortical hyperactivity have been associated to cognitive impairment for non-emotional ("cold") and emotional ("hot") working memory tasks in major depressive disorder (MDD). We investigated whether an increase of DLPFC activity using transcranial direct current stimulation (tDCS) would differently influence the performance in working memory tasks in depressed and healthy subjects. Forty young adult participants (20 with MDD and 20 healthy controls) were randomized to a single, sham-controlled, bifrontal (left anodal/right cathodal), 2mA, 30min tDCS session in a parallel design. The n-back and the internal shift task (IST) were used as proxies of cold and hot working memory performance, respectively. Active tDCS compared to sham promoted more accurate and faster responses to the n-back task for both patients and controls. Conversely, only patients presented an improvement in response times for the IST task. Our findings suggest that the mechanisms of tDCS in MDD involve modulation of both cold and hot working memory. We discuss these findings considering the modulatory top-down effects of tDCS on subcortical structures via prefrontal activation, and how spreading of activation might be different for healthy volunteers versus depressed patients. We also discuss the role of tDCS in cognitive amelioration for depressed patients. Finally, the distinct effects of tDCS in the "hot" cognition task for healthy and depressed participants are indicative that tDCS outcomes are also regulated by differences in baseline activity of the stimulated network.

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OBJECTIVES: Transcranial direct current stimulation (tDCS) is a neuromodulatory intervention with recent clinical trials showing promising results in major depression treatment. Although tDCS has some appealing characteristics (e.g., low cost, ease of use, and relatively benign profile of adverse effects), one important drawback of the technique is the need to deliver consecutive, repeated sessions for several weekdays. However, no study investigated whether absences during this acute treatment phase impact on tDCS efficacy, and, if so, whether absences should be considered dropouts, therefore increasing attrition. MATERIAL AND METHODS: To examine this issue, we used data from a randomized, factorial, sham-controlled tDCS study that recruited 120 depressed patients. In this trial, the acute treatment phase consisted of ten consecutive sessions delivered once daily from Monday to Friday; two nonconsecutive missed visits were allowed, with extra tDCS sessions being performed to complete the original number of sessions. RESULTS: Our main finding was that the procedure of granting one to two absences during the acute treatment phase did not impact on tDCS antidepressant efficacy. Moreover, out of 103 completers, only 41 (39.8%) patients presented no missing visits and 25 (24.3%) presented two absences. These patients did not differ in clinical and demographic characteristics; thus, absences were probably circumstantial (e.g., traffic congestion, personal obligations). CONCLUSIONS: Absences during the acute tDCS treatment phase are common, which support the use of flexible schedules in future tDCS trials as to minimize attrition. Also, further studies should access whether higher number of absences can compromise optimal tDCS efficacy.

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Background: Transcranial direct current stimulation (tDCS) is a novel non-pharmacological intervention being investigated for the treatment of major depressive disorder (MDD). Objective: To perform an updated review of tDCS for MDD. Method: Systematic review in Medline/PubMed and other databases of all clinical studies evaluating the clinical efficacy of tDCS in MDD, from the first date available to December/2013. Results: Out of 55 articles, 24 were included, being 6 open-label studies; 8 randomized, double-blind, sham-controlled trials; 2 follow-up studies; 2 meta-analyses and 6 case reports. We observed an improvement of 20-40% in depressive symptoms, being slightly better in open studies. Five randomized clinical trials displayed positive results. The meta-analyses presented mixed results; although none included the study of Brunoni et al. (2013) that represents almost 50% of the evaluated sample. Open-label studies and case reports also investigated tDCS in bipolar depression, post-stroke depression and employed different parameters of stimulation. Discussion: TDCS is a novel, promising treatment for MDD. Definite evidence from large, ongoing clinical trials will be available in the next years...

Contexto: A estimulação transcraniana por corrente contínua (ETCC) é uma nova intervenção não farmacológica investigada como tratamento no transtorno depressivo maior (TDM). Objetivo: Apresentar uma revisão atualizada da ETCC no TDM. Método: Revisão sistemática no banco de dados Medline/PubMed e outros de todos os estudos clínicos publicados avaliando a eficácia da ETCC no TDM, da primeira data disponível a dezembro/2013. Resultados : De 55 artigos, 24 foram incluídos, sendo 6 estudos abertos; 8 ensaios clínicos randomizados, duplo-cego, placebo controlados; 2 estudos de seguimento; 2 metanálises e 6 relatos de caso. Observa-se uma melhora de 20-40% nos sintomas depressivos, sendo ligeiramente maior nos estudos abertos. Entre os ensaios controlados, 5 demonstraram eficácia da técnica. As metanálises divergiram quanto aos resultados, mostrando presença e ausência de eficácia e ausência da ETCC. Porém, nenhuma incluiu o estudo de Brunoni et al. (2013), que representa quase 50% da população estudada. Estudos abertos e relatos de caso também investigaram o uso da ETCC na depressão bipolar, na depressão pós-AVC e usaram variações nos parâmetros de estimulação. Conclusões: A ETCC é uma técnica promissora no tratamento da TDM. Evidências definitivas devem estar disponíveis nos próximos anos, com a divulgação de resultados de grandes ensaios clínicos em andamento...

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