Meta-analysis concludes antidepressants more effective than placebo

A major meta-analysis, published in The Lancet, comparing 21 commonly used antidepressants concludes that all are more effective than placebo for the short term treatment of acute depression in adults, with effectiveness ranging from small to moderate for different drugs. Overall, 522 double-blind randomised controlled trials (RCTs) conducted between 1979 and 2016, comprising a total of 116 477 participants, were included in the meta-analysis, the largest ever in psychiatry. As part of the review, the authors identified all RCTs comparing antidepressants with placebo, or with another antidepressant for the acute treatment (over 8 weeks) of major depression in adults aged 18 years or more. The authors then contacted pharmaceutical companies, original study authors and regulatory agencies to supplement incomplete reports of the original articles or provide data for unpublished studies. The primary outcomes were efficacy (number of patients who responded to treatment; ie, patients who had a reduction in depressive symptoms of 50% or more on a validated rating scale over 8 weeks) and acceptability (proportion of patients who withdrew from the study for any reason by week 8). A total of 87 052 participants had been randomly assigned to receive a drug, and 29 425 to receive placebo. The majority of patients had moderate to severe depression. All 21 antidepressants were more effective than placebo, with odds ratios (ORs) ranging between 2.13 (95% credible interval [CrI], 1.89–2.41) for amitriptyline and 1.37 (95% CrI, 1.16–1.63) for reboxetine. Only agomelatine (OR, 0.84; 95% CrI, 0.72–0.97) and fluoxetine (OR, 0.88; 95% CrI, 0.80–0.96) were associated with fewer dropouts than placebo, whereas clomipramine was the only antidepressant that was less acceptable than placebo (OR, 1.30; 95% CrI, 1.01–1.68). Based on studies comparing one antidepressant with another, agomelatine, amitriptyline, escitalopram, mirtazapine, paroxetine, venlafaxine and vortioxetine were found to be the most effective, and fluoxetine, fluvoxamine, reboxetine and trazodone the least effective. The majority of the most effective antidepressants are now off-patent and available in generic form. Antidepressants also differed in terms of acceptability, with agomelatine, citalopram, escitalopram, fluoxetine, sertraline and vortioxetine proving most tolerable, and amitriptyline, clomipramine, duloxetine, fluvoxamine, reboxetine, trazodone and venlafaxine being the least tolerable.

Kids with CKD may have lower IQs and poorer educational outcomes

Researchers from the University of Sydney have found that children with chronic kidney disease (CKD) are at greater risk of deficits in academic skills, visual and verbal memory, and executive function. In a review published in the Clinical Journal of the American Society of Nephrology, the authors’ analysis included 34 studies of over 3000 children and adolescents under the age of 21 years. “The IQ of children with CKD is low to average,” says the study’s lead author, Dr Kerry Chen of the University of Sydney’s Centre for Kidney Research. Compared with healthy children, the IQs of children with CKD were on average 10 points lower regardless of their stage of kidney disease. The IQs of children who received a kidney transplant were 11 points lower than their healthy counterparts and, for those on dialysis, their IQs were 16 points lower. While the evidence is not conclusive, the authors have some hunches about how CKD might affect IQ and educational outcomes in children and young adults. “First, increased plasma levels of uremic solutes arising from kidney disease may impair synaptic development,” says Dr Chen. “Dialysis may also lead to cognitive impairment through rapid changes in blood pressure. Also, the pathological effects associated with end-stage kidney disease, such as anaemia, hypertension and malnutrition, may reduce cognitive function among children on dialysis compared with other CKD stages. On top of that, treatments for CKD may compromise academic achievement. The frequency of sleep disturbances in children with CKD may result in poor concentration, excessive daytime sleepiness and lower academic performance. The interactions of complex medication routines and strict dialysis cycles may decrease attentional control, working memory and executive function — cognitive domains that are important to children’s ability to acquire, understand and retain information in social and educational environments. Finally, ongoing dialysis sessions and recovery from transplant surgeries may reduce the amount and regularity of time spent in the classroom, with chronic absenteeism potentially preceding loss of interest, withdrawal and poor school progression.”

Global scale of tuberculosis in young people revealed in new report

An estimated 1.8 million young people around the world develop tuberculosis (TB) each year, according to a new report from University of Melbourne researchers, published in the European Respiratory Journal. The study is the first to estimate the global scale of the disease in people aged 10–24 years, a key demographic in its spread and prevention. Within this age group, those aged 20–24 years were found to be at the greatest risk of developing TB. The report uses figures from the World Health Organization Global TB database from 2012 and statistics from five countries that represented the global spread of TB epidemics: Brazil, Indonesia, South Africa, Romania and Estonia. The authors found that an estimated 1.05 million 20–24-year-olds, 535 000 15–19-year-olds, and 192 000 10–14-year-olds developed active TB, totalling 1.8 million new cases among young people a year. The actual figure could be as high as three million, they added. South Asia had the highest number of new cases with 721 000, followed by sub-Saharan Africa with 534 000. “Now that we have identified the scale of the problem, our next step is to try to understand the potential for targeting preventive measures specifically at young people in countries with intense TB epidemics,” said Ms Kathryn Snow from the Centre for International Child Health at the University of Melbourne and the Murdoch Children’s Research Institute.


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