An influential 2007 US National Institute of Mental Health-led study included a statistical manipulation that disguised the fact that youth taking antidepressants were actually over four times as likely to experience suicidal events as those taking placebo, according to a study in the International Journal of Risk & Safety in Medicine. This new published analysis has appeared several years after the revelations were first publicly discussed.
The seminal “Treatment for Adolescents With Depression Study (TADS)” published in JAMA Psychiatry in 2007 and involving researchers from NIMH and many universities, compared the effects on depression in teens of the antidepressant fluoxetine (FLX), cognitive behavioral therapy (CBT), placebo (PBO), and combined CBT and fluoxetine. A number of other reports on the TADS study were also published, including one in 2009 in the Journal of Clinical Psychiatry entitled, “Suicidal Events in the Treatment for Adolescents with Depression Study (TADS)”. Suicidal events were defined as “discrete episodes of suicidal ideation, suicidal attempts, or preparatory acts toward an imminent attempt”, and in the study over half of these events led to hospitalization of the youth. The NIMH-led study authors stated, though, that there were no significant differences in the rates of these suicidal events for youth taking either the antidepressant fluoxetine (Prozac) or placebo, and that, “Most suicidal events occurred in the context of persistent depression and insufficient improvement, without evidence of medication-induced behavioral activation as a precursor.”
However, a brief footnote to a table in the JCP study alerted child and adolescent psychiatrist Göran Högberg of Sweden’s Astrid Lindgren Children’s Hospital to a misleading way in which the data had been handled. On a table titled, “Suicidal Event Categories”, a footnote read, “Treatment at time of event was different from the randomized one for 3 CBT and 9 PBO patients, who had started antidepressant medication due to poor response to assigned treatment.”
Essentially, after 12 weeks of the 36-week TADS study, some of the youth who had been taking placebo started taking the antidepressant instead. And it was only after these youth started taking the drug that they experienced suicidal events. But the NIMH researchers had not included that fact in any of their analyses.
So Högberg and co-authors David Antonuccio and David Healy conducted a new analysis of the data based on this revelation. The NIMH researchers had reported that 16 youth on fluoxetine had experienced suicidal events compared to 12 youth taking placebo, a non-significant difference. But Högberg’s team found that, of those 12 in the placebo group, only 3 suicidal events actually took place while the youth were taking placebo, while the other 9 took place after they’d switched to fluoxetine. Consequently, they determined, the participants in the trial were in fact over four times as likely to experience suicidal events while taking the drug.
“The analysis of the data showed that there was a statistically significant difference in proportion of youths with suicidal events between the PBO condition (2.7%) and the FLX treatment (11%),” concluded Högberg’s team.
They added, “What we also did note was that the suicidal events in the study were evenly distributed over the entire time period; thus highlighting that the risk for suicidal events in SSRI-treated adolescents appears to be increased up to eight months after the start of medication.”
“None of the seven abstracts from TADS publications mentioned the fact that there were four times more suicidal events with fluoxetine than with placebo during the randomized controlled trial, and that this difference was statistically significant,” stated the researchers.
Prior to the study being published, these revelations from Högberg’s analysis were discussed several years ago in detail by MIA Blogger David Healy and in a post on Mad In America by MIA Publisher Robert Whitaker.
“Among the bizarre misrepresentations in Clinical Trials of psychiatric drugs during the Age of the Decepticons, this one may take the grand prize,” wrote 1 Boring Old Man recently about the NIMH study. Commenting on the new analysis appearing in the International Journal of Risk & Safety in Medicine, he wrote, “It’s years late, and it’s softly presented, but it’s still something of a breakthrough. It’s what we’re hoping for from Data Transparency, but they didn’t have to petition for the data or jump through any hoops as it was just hiding there in plain sight.”
Högberg, Göran, David O. Antonuccio and David Healy. “Suicidal risk from TADS study was higher than it first appeared.” International Journal of Risk & Safety in Medicine 27 (2015) 85–91 DOI 10.3233/JRS-150645 (Abstract)
the Age of the Decepticons… (1 Boring Old Man, June 18, 2015)
Vitiello, Benedetto, Susan Silva, Paul Rohde, Christopher Kratochvil, Betsy Kennard, Mark Reinecke, Taryn Mayes, Kelly Posner, Diane E. May, and John S. March. “Suicidal Events in the Treatment for Adolescents with Depression Study (TADS).” The Journal of Clinical Psychiatry 70, no. 5 (May 2009): 741–47. (Full text)
“The Treatment for Adolescents with Depression Study (tads): Long-Term Effectiveness and Safety Outcomes.” Archives of General Psychiatry 64, no. 10 (October 1, 2007): 1132–43. doi:10.1001/archpsyc.64.10.1132. (Full text)