“For young people with major depression,” the Washington Post reported earlier this month, “antidepressants may help little if at all.” From ABC News in Australia, the focus extended to more than the drugs’ limited efficacy; it included their risk of harm, including from side effects and heightened suicidality: “Antidepressants for kids and teens ineffective, may even be harmful, study finds.”
The study in question, published earlier this month in The Lancet and led by Dr. Andrea Cipriani at Oxford University, examined the effectiveness and potential harm associated with 14 SSRI and Tricyclic antidepressants, prescribed in large numbers to adolescents and children worldwide: amitriptyline, citalopram, clomipramine, desipramine, duloxetine, escitalopram, fluoxetine, imipramine, mirtazapine, nefazodone, nortriptyline, paroxetine, sertraline, and venlafaxine. The Lancet meta-analysis examined data from 34 earlier studies involving more than five thousand youths, most of them aged 9 to 18, who had moderate to severe symptoms and had received a diagnosis of major depression. As Linda Searing at the Washington Post reported, “In an average year, an estimated 2.8 million Americans age 12 to 17, or roughly 11 percent of that age group, have at least one depressive episode.”
The Lancet study is significant not just in scale but also in explicitly correcting for bias, as it incorporated the results of unpublished clinical trials while offsetting for the fact that drug companies had funded 65 percent of them. Even taking into account that figure, 88 percent of the trials indicated additional risk of bias (29 percent of them were at high risk, while the remaining 59 percent indicated a moderate risk of bias).
But it was the study’s conclusion that drove health headlines around the world, though the finding itself wasn't exactly news: only one of the drugs, fluoxetine (Prozac), was found to be marginally more effective than placebo at relieving depression, an advantage offset by the drug's substantial number of side effects, including an increased risk of suicidal thoughts.
Weighing risks relative to benefits, the researchers concluded that antidepressants “do not seem to offer a clear advantage for children and adolescents” with major depression. Additionally, Dr. Cipriani explained, “the selective reporting of findings in the published trials and clinical study reports” made claims on behalf of such research dubious and of low value scientifically.
Jon Jureidini, a professor at the University of Adelaide, wrote in commentary about the research that the findings had “disturbing implications for clinical practice ... as the risk-benefit profile of antidepressants in the acute treatment of depression does not seem to offer a clear advantage for children and adolescents.”
That conclusion—disturbing though well-publicized elsewhere and thus far from surprising—acquired greater urgency as ABC News highlighted prescribing patterns for Australian children and adolescents between 2009 and 2012, noting that the number of children aged 10 to 14 who had been given antidepressants in those years had jumped by more than a third.
Iain McGregor, a professor at the University of Sydney and co-author of the study that generated that finding, asked pointedly at the time, “Why are we so reliant on meds for our mental wellbeing?”
It's a question doctors and parents of the many thousands of children and adolescents given antidepressants studied doubtless need to be asking, especially with the latest meta-analysis one of many signaling that the drugs are neither effective nor without a substantial risk of harm.