Lexapro for Children: Drug With No Meaningful Benefit and Increased Suicidality Gets FDA Approval

In May, the FDA expanded the approval of pharma giant AbbVie’s SSRI escitalopram (Lexapro) to include kids ages seven and up who have anxiety. The basis for the approval was a clinical trial conducted by AbbVie employees, with an article written by AbbVie’s ghostwriting firm.

The researchers randomly assigned 275 kids aged 7-17 with a diagnosis of generalized anxiety disorder (GAD) to either receive Lexapro or a placebo. The trial lasted for eight weeks.

The findings were mixed. On the 30-point PARS-GAD anxiety measure, there was a mean difference of 1.42 points between the drug and placebo group (statistically significant at p <0.05, but not significant at p <0.01). This is the finding that supports the FDA’s approval.

However, the researchers also found that there was no difference between groups in response to the drug, remission from anxiety, and overall functioning. That is, about the same number of kids, whether on the drug or on placebo, experienced clinical improvement (“response”) or no longer had anxiety (“remission”). Nor did the drug improve overall functioning.

Concerningly, Lexapro also increased suicidality sixfold. In the escitalopram group, 9.5% of the kids became suicidal—compared with 1.5% in the placebo group. One patient actually attempted suicide in the escitalopram group (versus none in the placebo group).

This is especially notable since having a depression diagnosis or suicidal ideation were exclusion criteria for the study, meaning that the kids were not depressed or suicidal when they started the drug trial.

The researchers’ conclusions? Despite the same number of kids improving whether they received the drug or placebo and suicidality increasing sixfold in those who took the drug, they write:

SSRIs (like Lexapro), despite often being prescribed for people at risk of suicide, have been repeatedly shown to increase suicide risk, particularly for children and adolescents. That’s why the FDA has required a “black box warning” on SSRIs to let consumers know that the drugs make kids and teens suicidal.

Forest Labs (which was since bought by Allergan, which then merged with AbbVie) paid $313 million in 2010 for obstruction of justice, illegal marketing, kickbacks, and false insurance claims related to Lexapro and other drugs.

Among other controversies, AbbVie was forced to pay $24 million in 2018 and another $25 million in 2020 to settle lawsuits about illegal kickback practices and illegal marketing for its various drugs. Additionally, Allergan was one of the main firms accused of creating the opioid crisis by illegally marketing opioids. Last year, AbbVie agreed to pay $2.37 billion to settle these allegations.

The current study was published in the Journal of Child and Adolescent Psychopharmacology. Like most published reports of clinical trials of drugs today, the pharmaceutical company’s own employees were listed as authors, and it paid a medical writing company, Prescott Medical Communications Group, to write the article. Indeed, AbbVie made it clear that it controlled all aspects of the trial, writing that it “funded this study and participated in the study design, research, analysis, data collection, interpretation of data, and reviewing and approval of publication.”

The first author was Jeffrey R. Strawn at the University of Cincinnati Medical Center. While he is not an employee of AbbVie or the companies AbbVie paid to conduct the study, the paper’s disclosures state he has received research funds from Abbvie.

Authors Edward Greenberg, Chengcheng Liu, and Mallika Gopalkrishnan are direct AbbVie employees. Authors Leslie Moldauer, Rebekah D. Hahn, Alexandria Wise, Kristina Bertzos, and Beth Eisenberg are all employees of Syneos Health, a company funded by AbbVie to conduct the study. James A. Knutson, the paper’s last author, owns Core Clinical Research, another such company. Author Molly McVoy received a grant from The Hartwell Foundation, which focuses on expanding biomedical interventions in children.

Carol Brown, the Prescott Medical Communications employee who wrote the article, is not listed as an author. As is now usual for such “ghost authors,” she is instead acknowledged for her “writing and editorial assistance.”

It’s usually required for an article to specify what work each individual listed author did on the study and the article writing. Here’s that paragraph in this study:

As can be seen by this acknowledgment, there is no assertion that the named authors designed and conducted the study or that they wrote the article. The published article is AbbVie’s report of its trial, and not surprisingly, the article draws a conclusion that escitalopram is safe and effective in children, even though—in the same article—the published data tells of a drug treatment that is ineffective in children and increases the likelihood they will become suicidal. It is, of course, the conclusion that AbbVie will now use to market escitalopram for use in children.

 

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Strawn, J. R., Moldauer, L., Hahn, R. D., Wise, A., Bertzos, K., Eisenberg, B., & Knutson, J. A. (2023). A multicenter double-blind, placebo-controlled trial of escitalopram in children and adolescents with generalized anxiety disorder. Journal of Child and Adolescent Psychopharmacology, 33(3), 91-100. http://doi.org/10.1089/cap.2023.0004 (Link)