Most antidepressants on the market are ineffective for children and teens with major depressive disorder, and some may be unsafe for young patients, according to new research published in The Lancet.
The findings show that out of 14 antidepressants, only fluoxetine (sold under brand names Prozac and Sarafem) was more effective at relieving symptoms of depression in young people than a placebo pill. In contrast, taking venlafaxine (Effexor) was associated with an increased risk of suicidal thoughts and suicide attempts when compared to a placebo and five other antidepressants.
The researchers say their study is the most comprehensive analysis to date of commonly prescribed antidepressant use in children and teens. However, they caution that the drugs' true effectiveness and potential for harms remain unclear because only a limited amount of research has been done on antidepressant use in children and teens.
Major depressive disorder is relatively common in kids and adolescents, with estimates suggesting it affects about 3 percent of children aged 6 to 12, and 6 percent of teens aged 13 to 18, the authors note.
The U.S. National Institutes of Health reports that in 2014, an estimated 2.8 million adolescents aged 12 to 17 -- about 11 percent of this population -- had at least one major depressive episode.
Lead study author Dr. Andrea Cipriani of the University of Oxford in the U.K. points out that depression in young people is often very different than depression in adults. "Not only is it still under-diagnosed and under-treated but also it tends to present in a different way," he said in an interview with The Lancet. "Depressive symptoms in children and adolescents are rather undifferentiated. You notice more irritability, aggressive behavior and problems at school. And consequences of depressive episodes in children and adolescents are dramatic because they include impairments in their social functioning but also an increased risk of suicidal ideation and attempts."
International treatment guidelines for major depression recommend starting with a non-drug approach, such as cognitive behavioral or interpersonal therapy. Evidence shows such interventions work, "but also because with children and adolescents we are talking about a developing brain, so we are always very cautious when prescribing medications because we don't know the potential implications in the long term for a developing brain," Cipriani said.
In 2004, the U.S. Food and Drug Administration issued a "black box" warning for all antidepressant use in young people up to the age of 24 because of the risk the drugs may increase suicidal thinking and behavior.
Still, the use of antidepressants in kids and teens is slowly rising. One study published in March of this year, also in The Lancet, found antidepressant use increased from 1.3 to 1.6 percent in U.S. children and teens from 2005 to 2012.
For the study, Cipriani and his colleagues conducted a systematic review and analysis of all published and unpublished randomized clinical trials comparing the effects of 14 antidepressants in young people with major depressive disorder. The final analysis included 34 trials involving 5,260 participants.
They assessed the drugs on efficacy, tolerability (how many patients stopped taking them due to adverse events), acceptability (discontinuation due to any cause), and associated serious harms like suicidal thoughts and attempts.
The results showed that fluoxetine was the only antidepressant where the benefits outweighed the risks. Nortriptyline (sold as Pamelor) was "significantly less effective" than seven other antidepressants and a placebo pill. Imipramine (Tofranil), venlafaxine, and duloxetine (Cymbalta) were lowest rated for tolerability. Venlafaxine was also linked with an increased risk of suicidal thoughts or attempts.
Dr. Victor Fornari, director of the division of child and adolescent psychiatry at Zucker Hillside Hospital in Glen Oaks, New York, and Cohen Children's Medical Center in New Hyde Park, New York, said the study and its findings are very important.
"Depression in youth is a serious public health problem associated with the leading cause of death in this age group, suicide," he told CBS News. "Understanding what the evidence demonstrates is critical to guide treatment for this vulnerable population."
The authors also note that 65 percent of the trials in the review were funded by pharmaceutical companies. Furthermore, they used research tools to rate the risk of bias and overall quality of the studies analyzed. They found that the majority of studies had a high risk of bias and very low quality of evidence, suggesting the results have limited implications for clinical practice.
In an accompanying editorial, Dr. Jon Jureidini at the University of Adelaide in Australia questions how many more instances of suicidal thoughts or behavior might have been revealed had individual patient-data been available. He points out, "[For example], in four trials of paroxetine versus placebo, only 13 (3%) of 413 [suicidal] events were reported in the paroxetine group; this seems implausible when individual patient-level data reanalysis of just one of those studies found ten events in only 93 patients given paroxetine (10.8%)."
Furthermore, he adds: "The effect of misreporting is that antidepressants, possibly including fluoxetine, are likely to be more dangerous and less effective treatments than has been previously recognized, so there is little reason to think that any antidepressant is better than nothing for young people."
However, even if the study raises questions about the use of antidepressant drugs, Fornari emphasized that these results do not mean treating depression in children and adolescents should be any less of a priority.
"Careful monitoring is important in order to identify youth who may have the emergence of suicidal thoughts, in order to provide the proper level of care to insure safety," he said. "Failure to treat depression should not be the take-home of this study."