Reevaluation of Adolescent Depression Medication Trial Highlights Potential Risks of SSRIs

A comprehensive review conducted by researchers at the University of Adelaide has critically analyzed the widely cited 2007 clinical trial on treatments for adolescent depression, known as the Treatment for Adolescents with Depression Study (TADS). This pivotal trial, frequently leveraged by international health authorities to endorse the use of antidepressants for teenagers, specifically examined the effects of fluoxetine, a selective serotonin reuptake inhibitor (SSRI), in 439 adolescents aged 12 to 17.

In the original study, participants were assigned to one of four groups for a 12-week period: fluoxetine alone, cognitive behavioral therapy (CBT) alone, a combination of fluoxetine and CBT, or a placebo. The initial results indicated that combined therapy yielded superior outcomes, leading to widespread acceptance of antidepressant medication as an effective treatment for adolescent major depressive disorder (MDD), with the study being cited over 1,900 times.

However, under a meticulous reanalysis using the Restoring Invisible and Abandoned Trials (RIAT) methodology, Professor Jon Jureidini and his team revisited the original data to assess whether the trial’s findings were accurately represented. The reanalysis aimed to verify the true effectiveness and assess the safety profile of fluoxetine in this population.

The researchers confirmed that the combined treatment was indeed more effective, but crucially, they found no convincing evidence to support significant benefits of fluoxetine over placebo. More concerningly, the reanalysis revealed that serious adverse events, including suicidal behaviors, were more prevalent among adolescents receiving fluoxetine than originally reported. Documentation showed 32 serious adverse events, including at least three suicide attempts that were not clearly disclosed in the initial publication.

According to Professor Jureidini, these findings raise questions about the safety of prescribing fluoxetine to adolescents for depression. The study underscores the importance of rigorous data transparency and evaluation of potential harms, especially when medication is used in vulnerable populations.

This critical review suggests that while combining therapies may be beneficial, the risks associated with fluoxetine—particularly serious adverse events—may outweigh the benefits. It emphasizes the need for clinicians to carefully consider the safety profiles of antidepressants administered to teenagers and advocates for enhanced transparency in clinical trial reporting.

For more insights, the full reanalysis is published in the International Journal of Risk & Safety in Medicine (2025).