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Introduction:The use of ketamine as an option in the treatment of depressive disorder is growing rapidly, supported by numerous clinical trials attesting its efficacy and safety. Esketamine, the S (+) enantiomer of ketamine, is the most widely used form in the anesthetic environment in some countries, and new studies have shown that it may also be effective in depression and with better tolerability. However, no study so far has directly compared esketamine with racemic ketamine. Here we propose a protocol of a clinical trial to evaluate esketamine as a noninferior medication when compared to ketamine in the treatment of patients with treatment-resistant depression.Methods/design:This study protocol is for a randomized, controlled, double-blind noninferiority clinical trial. Subjects will be 18 years or older, with major depression characterized as treatment-resistant. Participants will receive a single infusion of either esketamine (0.25 mg/kg) or ketamine (0.5 mg/kg) over 40 minutes. The primary outcome will be the difference in remission rates between the 2 treatment arms at 24 and 72 hours after drug infusion. Secondary outcomes will include other timepoints, measurements of cognition, dissociation, and blood biomarkers.Discussion:A head-to-head study is the best way to evaluate whether the esketamine is in fact comparable to the racemic ketamine in terms of both efficacy and safety, and, if positive, it would be an initial step to increase the access to that type of treatment worldwide.Ethics and dissemination:The study was approved by the local Institutional Review Board (University Hospital Professor Edgard Santos—Federal University of Bahia—Number: 46657415.0.0000.0049). Subjects will only participate after voluntarily agreeing and signing the Informed Consent Form. The study findings will be published in peer-reviewed journals and presented at national and international conferences.Trial registration:This trial has been registered in the Japan Primary Registries Network (JPRN): UMIN000032355, which is affiliated with the World Health Organization.

Studies have demonstrated that, for urban children, dust represents the main exposure to sources of metals like lead (Pb) and manganese (Mn). We aimed to investigate the exposure to these metals and their association with intellectual deficit in children living in an industrial region. This cross-sectional study recruited volunteers from four elementary schools in the town of Simões Filho, Brazil. We evaluated 225 school-aged children (7–12 years) for blood lead (PbB) and manganese hair (MnH) and toenails (MnTn) by graphite furnace atomic absorption spectrometry. Child and maternal IQs were estimated using the Wechsler Abbreviated Scale for Intelligence (WASI). Median and range PbB were 1.2 (0.3–15.6) μg/dL. MnH and MnTn medians (ranges) were 0.74 (0.16–8.79) μg/g and 0.85 (0.15–13.30) μg/g, respectively. After adjusting for maternal IQ, age and Mn exposure, child IQ drops by 8.6 points for a 10-fold increase in PbB levels. Moreover, an effect modification of Mn co-exposure was observed. In children with low MnTn, association between Pb and child IQ was not significant (β = −6.780, p = 0.172). However, in those with high MnTn, the association was increased by 27.9% (β = −8.70, p = 0.036). Low Pb exposure is associated with intellectual deficit in children, especially in those with high MnTn.

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