{"id":66212,"date":"2016-06-09T22:05:45","date_gmt":"2016-06-10T02:05:45","guid":{"rendered":"http:\/\/1boringoldman.com\/?p=66212"},"modified":"2016-06-09T22:10:00","modified_gmt":"2016-06-10T02:10:00","slug":"antidepressants-in-kids-a-new-meta-analysis","status":"publish","type":"post","link":"https:\/\/1boringoldman.com\/index.php\/2016\/06\/09\/antidepressants-in-kids-a-new-meta-analysis\/","title":{"rendered":"antidepressants in kids? a new meta-analysis…"},"content":{"rendered":"\n

Note: The main article [Cipriani et al<\/font><\/em>] is available full text on line at the time I’m writing this, but I can’t tell for how long. If pediatric depression is of any interest to you, I would recommend saving it to your computer\/desktop as that access might disappear.<\/font><\/em><\/sup><\/p>\n

Andrea Cipriani<\/a> is an Oxford-based psychiatrist and author of numerous Systematic Reviews and Meta-analyses of psychiatric medications – many published by the Cochrane Collaboration. In short, he’s the real deal. I had an opportunity to see an advanced copy of this paper and my thought after reading it that this should be the  new gold standard for this much discussed topic. The accompanying comment by Jon Jureidini is quite good, though I can’t locate a full text source on-line. <\/p>\n

This has been such a conflicted issue from the earliest of days. Prozac® [fluoxetine] was approved for adolescent depression, then later Celexa®\/Lexapro® were approved around the same time that the FDA appended the Black Box warning in 2004. No other SSRI\/SNRI drugs have been approved for kids since then. This is a highly contentious issue ["this" being Are the drugs safe in kids?<\/font><\/em> Are the drugs even effective in kids?<\/font><\/em> Do they cause suicidality in some kids? suicides?<\/font><\/em> homicides?<\/font><\/em>]. <\/p>\n

Cipriani et al are definite about their results ["…these drugs do not seem to offer a clear advantage for children and adolescents<\/font><\/em>"]. So the real question is what do you do if you don’t prescribe antidepressants to depressed teens? What’s the alternative? But that’s for another day. Here’s their meta-analysis, with a few bells and whistles, and some American Academy of Child and Adolescent Psychiatry<\/font><\/em> practice guideline documents:<\/div>\n
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Comparative efficacy and tolerability of antidepressants for major depressive disorder in children and adolescents: a network meta-analysis<\/a><\/div>\n
by Andrea Cipriani, Xinyu Zhou, Cinzia Del Giovane, Sarah E Hetrick, Bin Qin, Craig Whittington, David Coghill, Yuqing Zhang, Philip Hazell, Stefan Leucht, Pim Cuijpers, Juncai Pu, David Cohen, Arun V Ravindran, Yiyun Liu, Kurt D Michael, Lining Yang, Lanxiang Liu, and Peng Xie<\/div>\n
Lancet.<\/font><\/strong> Published online June 8, 2016<\/div>\n
[full text on-line<\/a>]<\/div>\n
[audio interview<\/font><\/a>]<\/div>\n

<\/p>\n

Background<\/font><\/strong>: Major depressive disorder is one of the most common mental disorders in children and adolescents. However , whether to use pharmacological interventions in this population and which drug should be preferred are still matters of controversy. Consequently, we aimed to compare and rank antidepressants and placebo for major depressive disorder in young people. <\/div>\n
Methods<\/font><\/strong>: We did a network meta-analysis to identify both direct and indirect evidence from relevant trials. We searched PubMed, the Cochrane Library, Web of Science, Embase, CINAHL, PsycINFO, LiLACS, regulatory agencies’ websites, and international registers for published and unpublished, double-blind randomised controlled trials up to May 31, 2015, for the acute treatment of major depressive disorder in children and adolescents. We included trials of amitriptyline, citalopram, clomipramine, desipramine, duloxetine, escitalopram, fluoxetine, imipramine, mirtazapine, nefazodone, nortriptyline, paroxetine, sertraline, and venlafaxine. Trials recruiting participants with treatment-resistant depression, treatment duration of less than 4 weeks, or an overall sample size of less than ten patients were excluded. We extracted the relevant information from the published reports with a predefi ned data extraction sheet, and assessed the risk of bias with the Cochrane risk of bias tool. The primary outcomes were efficacy [change in depressive symptoms] and tolerability [discontinuations due to adverse events]. We did pair-wise meta-analyses using the random-effects model and then did a random-effects network meta-analysis within a Bayesian framework. We assessed the quality of evidence contributing to each network estimate using the GRADE framework. This study is registered with PROSPERO, number CRD42015016023.<\/div>\n
Findings<\/font><\/strong>: We deemed 34 trials eligible, including 5260 participants and 14 antidepressant treatments. The quality of evidence was rated as very low in most comparisons. For efficacy, only fluoxetine was statistically significantly more effective than placebo [standardised mean difference –0·51, 95% credible interval [CrI] –0·99 to –0·03]. In terms of tolerability, fluoxetine was also better than duloxetine [odds ratio [OR] 0·31, 95% CrI 0·13 to 0·95] and imipramine [0·23, 0·04 to 0·78]. Patients given imipramine, venlafaxine, and duloxetine had more discontinuations due to adverse events than did those given placebo [5·49, 1·96 to 20·86; 3·19, 1·01 to 18·70; and 2·80, 1·20 to 9·42, respectively]. In terms of heterogeneity, the global I² values were 33·21% for efficacy and 0% for tolerability.<\/div>\n
Interpretation<\/font><\/strong>: When considering the risk–benefit profile of antidepressants in the acute treatment of major depressive disorder, these drugs do not seem to offer a clear advantage for children and adolescents. Fluoxetine is probably the best option to consider when a pharmacological treatment is indicated.<\/div>\n<\/blockquote>\n
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Antidepressants fail, but no cause for therapeutic gloom<\/a><\/div>\n
by Jon Jureidini<\/div>\n
Lancet<\/font><\/strong>. Published online June 8, 2016<\/div>\n

<\/p><\/blockquote>\n

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Most antidepressants are ineffective in children and teenagers, study shows<\/a><\/div>\n
by Susan Mayor <\/div>\n
British Medical Journal<\/font><\/strong>. Published 09 June 2016<\/div>\n

<\/p><\/blockquote>\n

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Most antidepressants ineffective for children and teens<\/a><\/div>\n
The Pharmaceutical Journal<\/font><\/strong><\/div>\n
By Debbie Andalo<\/div>\n
9 JUN 2016<\/div>\n

Most antidepressants prescribed for children and adolescents with major and acute depressive disorders are ineffective, according to research published in The Lancet. Following a meta-analysis of data from 34 trials including 5,260 patients, researchers concluded that only fluoxetine was more effective than placebo in relieving symptoms in these young patients.<\/p>\n

“Antidepressants in the acute treatment of major depressive disorder… do not seem to offer a clear advantage for children and adolescents,” say the researchers, led by Andrea Cipriani, department of psychiatry, University of Oxford, and Xinyu Zhou, department of neurology and psychiatry, the First Affiliated Hospital of Chongqing Medical University, China. “Fluoxetine is probably the best option to consider when a pharmacological treatment is indicated,” they conclude…<\/p>\n

But the researchers warn that the quality of the evidence was “very low” and poor study design makes it difficult to give a true and confident picture about the effectiveness and potential harm of these drugs for children and young people.“We cannot rule out the possibility that some unpublished studies are still missing or that published reports might overestimate the efficacy of treatments,” they say…<\/p>\n

In an accompanying comment piece, Jon Jureidini, from the Critical and Ethical Mental Health research group at the Robinson Research Institute at the University of Adelaide, Australia, says the findings reinforce the need for independent researchers to be given access to individual patient level data in order to inform their research… Jureidini adds that the effect of misreporting is that antidepressants, possibly including fluoxetine, are likely to be more dangerous and less effective treatments than has been previously recognised. “There is little reason to think that any antidepressant is better than nothing for young people,” Jureidini concludes.<\/p>\n

Katherine Delargy, deputy chief pharmacist at Barnet, Enfield and Haringey mental health NHS Trust, described the meta-analysis results as “important” but asks for more research to be carried out…<\/p>\n

Steve Bazire, former chief pharmacist at Norfolk and Waveney Mental Healthcare Partnership NHS Trust, questions some of the reviewers’ conclusions: “The paper doesn’t necessarily show that antidepressants don’t work, just that we can’t prove or disprove it yet as the evidence was classed as very low quality.” He also queries the researchers’ suggestion that the first choice for adolescent depression should be “evidence-based psychotherapy”…<\/p>\n

Bazire points out that previous research that directly compared drugs with cognitive behavioural therapy (CBT) showed that drug therapy is more effective. “So if antidepressants don’t work, neither does CBT,” he says. However, he acknowledges the dangers of antidepressant use and says they must be used with caution, starting with low doses and slowly increasing the dose to avoid any akathisia or heightened anxiety. “Patients must also be monitored for akathisia linked with suicide,” he adds. <\/div>\n<\/blockquote>\n
For Reference:<\/font><\/strong><\/div>\n