Alessandra C. Goulart

The Sertraline vs Electrical Current Therapy for Treating Depression Clinical Study Results From a Factorial, Randomized, Controlled Trial

IMPORTANCE Transcranial direct current stimulation (tDCS) trials for major depressive disorder (MDD) have shown positive but mixed results. OBJECTIVE To assess the combined safety and efficacy of tDCS vs a common pharmacological treatment (sertraline hydrochloride, 50 mg/d). DESIGN Double-blind, controlled trial. Participants were randomized using a 2 × 2 factorial design to sertraline/placebo and active/sham tDCS. SETTING Outpatient, single-center academic setting in São Paulo, Brazil. PARTICIPANTS One hundred twenty antidepressant-free patients with moderate to severe, nonpsychotic, unipolar MDD. INTERVENTIONS Six-week treatment of 2-mA anodal left/cathodal right prefrontal tDCS (twelve 30-minute sessions: 10 consecutive sessions once daily from Monday to Friday plus 2 extra sessions every other week) and sertraline hydrochloride (50 mg/d). MAIN OUTCOME MEASURES In this intention-to-treat analysis, the primary outcome measure was the change in Montgomery-Asberg depression rating scale score at 6 weeks (end point). We considered a difference of at least 3 points to be clinically relevant. The analysis plan was previously published. Safety was measured with an adverse effects questionnaire, the young mania rating scale, and cognitive assessment. Secondary measures were rates of clinical response and remission and scores on other scales. RESULTS At the main end point, there was a significant difference in Montgomery-Asberg depression rating scale scores when comparing the combined treatment group (sertraline/active tDCS) vs sertraline only (mean difference, 8.5 points; 95% CI, 2.96 to 14.03; P = .002), tDCS only (mean difference, 5.9 points; 95% CI, 0.36 to 11.43; P = .03), and placebo/sham tDCS (mean difference, 11.5 points; 95% CI, 6.03 to 17.10; P < .001). Analysis of tDCS only vs sertraline only presented comparable efficacies (mean difference, 2.6 points; 95% CI, -2.90 to 8.13; P = .35). Use of tDCS only (but not sertraline only) was superior to placebo/sham tDCS. Common adverse effects did not differ between interventions, except for skin redness on the scalp in active tDCS (P = .03). There were 7 episodes of treatment-emergent mania or hypomania, 5 occurring in the combined treatment group. CONCLUSIONS AND RELEVANCE In MDD, the combination of tDCS and sertraline increases the efficacy of each treatment. The efficacy and safety of tDCS and sertraline did not differ. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01033084.

Afericoes e exames clinicos realizados nos participantes do ELSA-Brasil

The article describes assessments and measurements performed in the Brazilian Longitudinal Study for Adult Health (ELSA-Brasil). Some assessments including anthropometric assessment, casual blood pressure measurement, and ankle-brachial index have an established clinical application while others including pulse wave velocity, heart rate variability, and carotid intima-media thickness have no established application and do not have reference values for healthy Brazilian population but may be important predictors of cardiovascular outcomes. Blood pressure measurement following postural change maneuver was included in the ELSA-Brasil because it has not been much tested in epidemiological studies. Innovative approaches were developed for assessing the ankle-brachial index using an automatic device instead of the mercury column to measure blood pressure and for assessing the anterior-posterior diameter of the right lobe of the liver by ultrasound for quantitative assessment of nonalcoholic fatty liver disease. All ELSA-Brasil subjects were younger (35 years or more) than those included in other cohorts studying subclinical atherosclerosis. The inclusion of younger individuals and a variety of assessments make the ELSA-Brasil a relevant epidemiology study nationwide and worldwide.

Heart rate variability is a trait marker of major depressive disorder: evidence from the sertraline vs. electric current therapy to treat depression clinical study

Decreased heart rate variability (HRV) is a cardiovascular predictor of mortality. Recent debate has focused on whether reductions in HRV in major depressive disorder (MDD) are a consequence of the disorder or a consequence of pharmacotherapy. Here we report on the impact of transcranial direct current stimulation (tDCS), a non-pharmacological intervention, vs. sertraline to further investigate this issue. The employed design was a double-blind, randomized, factorial, placebo-controlled trial. One hundred and eighteen moderate-to-severe, medication-free, low-cardiovascular risk depressed patients were recruited for this study and allocated to either active/sham tDCS (10 consecutive sessions plus two extra sessions every other week) or placebo/sertraline (50 mg/d) for 6 wk. Patients were age and gender-matched to healthy controls from a concurrent cohort study [the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)]. The impact of disorder, treatment and clinical response on HRV (root mean square of successive differences and high frequency) was examined. Our findings confirmed that patients displayed decreased HRV relative to controls. Furthermore, HRV scores did not change following treatment with either a non-pharmacological (tDCS) or pharmacological (sertraline) intervention, nor did HRV increase with clinical response to treatment. Based on these findings, we discuss whether reduced HRV is a trait-marker for MDD, which may predispose patients to a host of conditions and disease even after response to treatment. Our findings have important implications for our understanding of depression pathophysiology and the relationship between MDD, cardiovascular disorders and mortality.

Sertraline vs. ELectrical Current Therapy for Treating Depression Clinical Trial - SELECT TDCS: Design, rationale and objectives

BACKGROUND Despite significant advancements in psychopharmacology, treating major depressive disorder (MDD) is still a challenge considering the efficacy, tolerability, safety, and economical costs of most antidepressant drugs. One approach that has been increasingly investigated is modulation of cortical activity with tools of non-invasive brain stimulation - such as transcranial magnetic stimulation and transcranial direct current stimulation (tDCS). Due to its profile, tDCS seems to be a safe and affordable approach. METHODS AND DESIGN The SELECT TDCS trial aims to compare sertraline vs. tDCS in a double-blinded, randomized, factorial trial enrolling 120 participants to be allocated to four groups to receive sertraline+tDCS, sertraline, tDCS or placebo. Eligibility criteria are moderate-to-severe unipolar depression (Hamilton Depression Rating Scale >17) not currently on sertraline treatment. Treatment will last 6weeks and the primary outcome is depression change in the Montgomery-Asberg Depression Rating Score (MADRS). Potential biological markers that mediate response, such as BDNF serum levels, Val66Met BDNF polymorphism, and heart rate variability will also be examined. A neuropsychological battery with a focus on executive functioning will be administered. DISCUSSION With this design we will be able to investigate whether tDCS is more effective than placebo in a sample of patients free of antidepressants and in addition, we will be able to secondarily compare the effect sizes of sertraline vs. tDCS and also the comparison between tDCS and combination of tDCS and sertraline.

THE SERTRALINE VERSUS ELECTRICAL CURRENT THERAPY FOR TREATING DEPRESSION CLINICAL STUDY (SELECT-TDCS): RESULTS OF THE CROSSOVER AND FOLLOW-UP PHASES

Transcranial direct current stimulation (tDCS) is a promising nonpharmacological therapy for major depression. In the Sertraline versus Electrical Current Therapy for Treating Depression Clinical Trial (SELECT‐TDCS) trial, phase‐I (Brunoni et al., JAMA Psychiatry, 2013) we found that tDCS is effective for the acute episode. Here, we describe tDCS effects during phases II (crossover) and III (follow‐up) of this trial (NCTs: 01149889 and 01149213).

Race, gender and stroke subtypes mortality in São Paulo, Brazil

Stroke mortality rates have a discrepant distribution according to socioeconomic variables as social exclusion in Brazil. Recently, data from race has been available from the official health statistics considering five categories: White, Mixed, Black, Asian and Native. We addressed in the city of São Paulo, Brazil, an analysis of cerebrovascular mortality according to race (excluding Asian and Native due to small number of events) and gender during 1999-2001 for people aged 30 to 79 years-old. For all cerebrovascular diseases, age-adjusted mortality rates (x 100,000) for men were higher for Black (150.2), intermediate for Mixed (124.2) and lower for White (104.5) people. These gradient patterns were similar for all stroke subtypes, except for subarachnoideal hemorrhage in which no differences were detected. For women, the rates were lower compared to men and the same pattern was observed among Black (125.4), Mixed (88.5) and White (64.1) women. Compared to White men, the risk ratio of Black men was 1.4. However, compared to White women, the risk ratio for Black women was 2.0. Concluding, there is a significant gradient of stroke mortality according to race, mainly among women.

A reappraisal of stroke mortality trends in Brazil (1979-2009)

Background Brazil has one of the highest cerebrovascular death rates in the Western Hemisphere. We investigated temporal trends according to gender and stroke subtypes. Methods We analyzed mortality rates between 1979 and 2009 for different stroke subtypes. Data were stratified by gender and age (35–74 years). The annual percent change and significant changes in the trends were identified with Poisson regression. Results After excluding deaths due to sequel from stroke for men, the annual percent changes (95% confidence intervals) were as follows: 1979–1984, 0·7 (−0·8 to 2·1); 1984–1994, −1·8 (−2·4 to −1·2); 1994–2007, −5·0 (−5·4 to −4·7); and 2007–2009, −0·8 (−7·0 to 5·8). For women, the annual percent changes were as follows: 1979–1994, −1·9 (−2·2 to −1·6); 1994–1997, −7·5 (−14·0 to −0·6); 1997–2007, −4·0 (−4·6 to −3·3); and 2007–2009, 1·6 (−5·5 to 9·2). For the 2006–2009 period, the average annual percent change (95% confidence interval) for all strokes was −3·1 (−3·3 to −2·9) for men and −2·9 (−3·1 to −2·8) for women. For the same period, the average annual percent change of death rates for stroke subtypes were, for men and women, respectively: intracerebral hemorrhage, −4·0 (−4·9 to −3·1) and −2·9 (−3·4 to −2·3); and ischemic stroke, −3·2 (−3·3 to −3·0) and −1·4 (−2·0 to −0·9). Conclusion Stroke mortality rates are declining in Brazil for all stroke subtypes.

Prevalence of thyroid disorders among older people: results from the São Paulo Ageing & Health Study

This study aimed to estimate prevalence of thyroid disorders in the São Paulo Ageing & Health Study, an epidemiological study addressing several health-adverse outcomes among elderly people living in a poor area of São Paulo, Brazil. All participants answered a questionnaire and had a blood sample collected to assess levels of thyrotropic hormone and free-thyroxine. Among 1,373 people (60.8% women), prevalence rates (95% confidence interval) for thyroid dysfunction (%) were: overt hyperthyroidism, 0.7% (0.2-1.1)[women: 0.8% (0.2-1.5); men: 0.4% (0.01-0.9)]; overt hypothyroidism, 5.7% (4.5-6.9) [women: 5.9% (4.3-7.5); men: 5.4% (3.5-7.3)]; subclinical hyperthyroidism, 2.4% (1.6-3.2) [women: 2.8% (1.6-3.9); men: 1.9% (0.7-3.0)]; and subclinical hypothyroidism, 6.5% (5.2-7.8) [women: 6.7% (5.0-8.4); men: 6.1% (4.1-8.2)]. There was no difference in prevalence rates according to gender, but almost 40% of women were diagnosed and under treatment compared to 9% of men. The burden of thyroid disorders in this sample is high and most participants were not aware of them.

Estratégias e desenvolvimento de garantia e controle de qualidade no ELSA-Brasil

The ELSA-Brasil (Estudo Longitudinal de Saude do Adulto - Brazilian Longitudinal Study for Adult Health) is a cohort study composed of 15,105 adults followed up in order to assess the development of chronic diseases, especially diabetes and cardiovascular disease. Its size, multicenter nature and the diversity of measurements required effective and efficient mechanisms of quality assurance and control. The main quality assurance activities (those developed before data collection) were: careful selection of research instruments, centralized training and certification, pretesting and pilot studies, and preparation of operation manuals for the procedures. Quality control activities (developed during data collection and processing) were performed more intensively at the beginning, when routines had not been established yet. The main quality control activities were: periodic observation of technicians, test-retest studies, data monitoring, network of supervisors, and cross visits. Data that estimate the reliability of the obtained information attest that the quality goals have been achieved.

A Stepwise Approach to Stroke Surveillance in Brazil: the EMMA (Estudo de Mortalidade E Morbidade Do Acidente Vascular Cerebral) Study

Background: Stroke mortality rates in Brazil are the highest in the Americas. Deaths from cerebrovascular disease surpass coronary heart disease. Aim: To verify stroke mortality rates and morbidity in an area of São Paulo, Brazil, using the World Health Organization Stepwise Approach to Stroke Surveillance. Methods: We used the World Health Organization Stepwise Approach to Stroke Surveillance structure of stroke surveillance. The hospital-based data comprised fatal and nonfatal stroke (Step 1). We gathered stroke-related mortality data in the community using World Health Organization questionnaires (Step 2). The questionnaire determining stroke prevalence was activated door to door in a family-health-programme neighbourhood (Step 3). Results: A total of 682 patients 18 years and above, including 472 incident cases, presented with cerebrovascular disease and were enrolled in Step 1 during April–May 2009. Cerebral infarction (84.3%) and first-ever stroke (85.2%) were the most frequent. In Step 2, 256 deaths from stroke were identified during 2006–2007. Forty-four per cent of deaths were classified as unspecified stroke, 1/3 as ischaemic stroke, and 1/4 due to haemorrhagic subtype. In Step 3, 577 subjects over 35 years old were evaluated at home, and 244 cases of stroke survival were diagnosed via a questionnaire, validated by a board-certified neurologist. The population demographic characteristics were similar in the three steps, except in terms of age and gender. Conclusion: By including data from all settings, World Health Organization stroke surveillance can provide data to help plan future resources that meet the needs of the public-health system.