Majority of Pediatric Antidepressant Industry Trials Considered Low Quality

Meta-analyses including studies that detail these trials could be presenting misleading information

Marta Pagán-Ortiz
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A new review published in the American Journal of Psychiatry highlights concerns regarding the reliance on industry-sponsored trials to justify the use of antidepressants with children and teenagers. The author, Dr. John T. Walkup of Weill Cornell Medicine, found that industry trials for these medications have significant weaknesses that should have led to the designation of these as failed trials, which should not be eligible for inclusion in meta-analyses on efficacy. In a press release to Medscape Medical News, Dr. Walkup explains that these industry trials do not provide accurate information about effectiveness in this population.

“To truly understand the evidence base for the treatment of teen depression, one should focus on the federally funded studies of teen depression, not the large number of failed industry-sponsored pediatric depression trials.”

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In this review, Dr. Walkup described the complex regulatory context surrounding these trials, offering an essential background to understand the antidepressant literature. He discusses the meta-analyses that include these trials and the methodological strengths and weaknesses of particular studies. In this way, he is able to compare the methodology and results of those trials sponsored by pharmaceutical industries, and those funded by the National Institute of Mental Health.

He found that industry-sponsored trials (N=16) had many implementation challenges and that their results are largely uninformative. Although many of these are considered negative trials, given that they did not prove efficacy, Dr. Walkup believes the methodology issues make them ineligible for inclusion in meta-analyses and would classify these as failed trials, due to their methodological weaknesses. The review concludes with a reminder that some high-quality trials have found antidepressants efficacious in this population, but that clinicians should maintain a balanced and broad perspective.

Depression is commonly diagnosed disorder in children and adolescents. The National Institute of Mental Health reported that in 2015 12.5% of the U.S. population aged 12-17 had at least one depressive episode in the last year. Given these numbers and the use of antidepressants in this population, research has been developing towards understanding the efficacy of these medications and concerns surrounding them.

A prior review led by Dr. Andrea Cipriani, published in 2016, found that the use of antidepressants in children and adolescents is not clearly beneficial and can, in fact, be harmful. Antidepressants, they found, were not effective, minimally effective, or just as effective as placebos but with adverse events. Further, this review also discussed the high-risk of bias considering the industry’s role in the trials. Other studies have pointed out the risks of antidepressants in regards to their lack of efficacy and the role of these in the development of chronic illnesses.

 

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Walkup, J. T. (2017). Antidepressant efficacy for depression in children and adolescents: industry-and NIMH-funded studies. American Journal of Psychiatry, appi-ajp. (Abstract)

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Marta Pagán-Ortiz
MIA-UMB News Team: Marta E. Pagán-Ortiz is a doctoral student and research assistant in the Counseling and School Psychology PhD program at UMass Boston. Marta is currently working on research studies related to mental health treatment guidelines for chronic illnesses, issues of structural violence within minority populations, and the reduction of disparities in mental health status and care.

7 COMMENTS

  1. This is an incredibly concerning publication. “It is the premise of this review that meta-analyses that include the large number of industry-sponsored antidepressant trials distort the picture of antidepressant efficacy for teen depression.” It is clearly intended to reverse the increasing reluctance of doctors to prescribe SSRI/SNRIs to children and adolescents, thanks to excellent and solid studies such as Cipriani et al’s Lancet 2016 (no benefit), and Sharma et al’s BMJ 2016 (double the risk of suicidality and aggression). The author was part of the TADS study, which has been noted on this site to have been grossly misreported – https://www.madinamerica.com/2012/02/the-real-suicide-data-from-the-tads-study-comes-to-light/ and this should be weighed when considering his opinion that these clearly ineffective dangerous drugs have “a broad and important role for antidepressant medications in pediatric internalizing conditions.”

    This “review” was, I suppose, inevitable, and will naturally be hugely reprinted and broadly distributed to GPs and psychiatrists by every pharmaceutical company with SSRI/SNRIs selling in the child/adolescent population. That is their marketing role (and sadly of this publication). The “accompanying editorial” serves the same purpose – from Medscape “Daniel Pine, MD, of the NIMH Intramural Research Program, and Robert Freedman, MD, of the University of Colorado School of Medicine in Aurora, note that some clinicians working with children and adolescents might have hesitated before recommending an SSRI, because of continued questioning in the media of the evidence for their effectiveness. This review “helps to generate a more balanced perspective, which promises to reduce the burden facing these clinicians,” they write. How fortunate for those clinicians do no longer face such a “burden” in prescribing drugs without an evidence-based of efficacy, but clear and well published evidence-base of harm to children/adolescents.

    I do not have the time to dissect either paper, or editorial, nor chase down the 3 authors declared disclosures, and industry ties including funding of their research programs, but it is very important for those psychiatrists and other concerned doctors who might have time and inclination to investigate, publish and broadly publicise a thorough evidence and science-based rebuke to these flimsy opinion based promotions of the prescription of SSRI/SNRIs to children/adolescents.

    • Rob, I couldn’t agree more with your comments. Walkup’s use of the term “failed trial” concerns me greatly. This term appears synonymous with the discredited notion of “assay sensitivity,” and scientifically speaking both terms are highly problematic. Walkup is basically saying that we should disregard results from many “antidepressant” trials in which the drug failed to outperform placebo. Antidepressants work, he assumes, so therefore clinical trials that do not show this are “failed” and their results can be ignored. Instead, we’re meant to only consider findings from a few positive trials. Such “counting the hits and forgetting the misses” is a cardinal feature of pseudoscience and a recipe for obscuring the truth.

      Walkup is certainly correct that most drug trials for pediatric depression are conducted by drug companies and have all manner of design and reporting biases that favor the drug over placebo. Given how much the deck is stacked in their favor in such trials, I find it remarkable that “antidepressants” consistently perform so poorly. Rather than being uninformative, I think such outcomes speak volumes about the effectiveness of these drugs in young people.

      If we’re meant to focus our analysis of “antidepressants” on just a few trials, principally the TADS study, then let’s have an honest conversation about the findings. For example, in the TADS study, CBT was as effective as Prozac at 18 weeks and during the year-long follow-up period. Suicidal events occurred in a whopping 16.7% of clients taking Prozac, compared to 3.6% of those who did not take Prozac. When comparing outcomes directly between the Prozac and placebo conditions, the rate of suicidal ideation and attempts was 11.2% higher among youth on Prozac. Walkup did not mention these findings in his paper, and instead characterised the results as demonstrating “good efficacy for antidepressant medications in pediatric depression.”

  2. On the news last night, in the city where I live, there was a report concerning how the suicide rate for girls 10-14 years of age has skyrocketed over the past decade. The doctor being interviewed claimed that this is due to social media. Bullying on social media certainly is a problem, but I suspect that this rise in deaths probably follows fairly well the rise in the number of girls in this age group being drugged with SSRI’s. And I wonder how many of these girls were labeled as “bi-polar” as a child, thanks to dear quack Joseph Beiderman, which then led to them being put on things like neuroleptics. And then we have the rise of the supposed ADHD label for girls where you get legal speed along with your drug cocktail.

    It always interests me that they never look at their contribution to all this and always point out other things to be the cause of the problem. Kids should not be given “anti-depressants”, period. Is growing up difficult for kids these days? Yes, absolutely. But we are not doing them a favor by filling them full of drugs that supposedly take care of some kind of broken brain due to chemical imbalances. What a bunch of bull manure.

  3. And explain to me again why we should pay any attention at all to studies and trials done by drug companies. Anyone with a lick of sense knows that you can’t trust any studies done by the drug companies since they have a vested interest to make money for their investors and so that the CEO’s of said companies can rake in millions of dollars in salaries and bonuses. I think we should call for an immediate stop to the prescription of these devil’s tic tacs to kids, period. If adults want to take them, after being informed of the fact that they don’t work and they cause horrific effects to deal with, that’s just fine. But they should never be forced on kids.

    • Stephen – the trouble is this review is saying the pharma funded studies are indeed not valid, and the NIMH studies “show” on the other hand that SSRIs help kids. It is thus especially sneaky, and will hook folks into thinking it’s “on the side of good” whilst advocating MORE use of drugs proven to be unhelpful and proven also of course to be significantly harmful.